Depression Book 1 3 (2015)

CENTRE FOR PHARMACY
POSTGRADUATE EDUCATION
Depression
A CPPE focal point programme

for pharmacy students
Book
UG500124/1
March 2015
CPPE FP_Depression_Book 1.indd 1
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Depression Book 1
Content contributors
Celia Feetam FCMHP, specialist mental health pharmacist
Terri Turner, locality lead pharmacist, Avon and Wiltshire Mental Health Partnership NHS Trust
CPPE programme developer
Samantha White, regional manager, CPPE
Reviewers
Stephen Bleakley, deputy chief pharmacist, Southern Health NHS Foundation Trust, and director, College of
Mental Health Pharmacy
Graham Newton, principal clinical pharmacist, Mental Health Services, 5 Boroughs Partnership NHS
Foundation Trust
CPPE reviewers
Anne Cole, regional manager, CPPE
Chris Cutts, director, CPPE
Geraldine Flavell, regional manager, CPPE
Piloted by
Kathleen Pritchard, tutor, CPPE
Disclaimer
We have developed this learning programme to support your practice in this topic area. We recommend
that you use it in combination with other established reference sources. If you are using it significantly after
the date of initial publication, then you should refer to current published evidence. CPPE does not accept
responsibility for any errors or omissions.
External websites
CPPE is not responsible for the content of any non-CPPE websites mentioned in this programme or for the
accuracy of any information to be found there.
All web links were accessed on 24 March 2015.
Brand names and trademarks
CPPE acknowledges the following brand names and registered trademarks mentioned throughout this
programme: DSM-IV, DSM-5TM and Valdoxan.
Published in March 2015 by the Centre for Pharmacy Postgraduate Education, Manchester Pharmacy
School, The University of Manchester, Oxford Road, Manchester, M13 9PT.
www.cppe.ac.uk
Production
Design & artwork by Gemini West Ltd
Printed by Gemini Print Ltd
Printed on FSC certified paper stocks using vegetable based inks.
Copyright Controller HMSO 2015
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Learning with CPPE
About CPPE focal point programmes
About this focal point programme on depression
Learning objectives
Useful resources
Checklist for planning
Moving into focus
10
What do you want to learn?
11
Reading, practice points and talking points
12
Directing change
42
Checklist for action
43
References
44
Depression Book 1
Contents
Welcome to the pharmacy student edition of CPPE focal point

The Centre for Pharmacy Postgraduate Education (CPPE) has revised this
learning programme for pharmacy students.
You can use it in three ways:
nS
elf-study: You can work through the reading, activities and cases alone.
nU
niversity-led event: Your university may have asked you to complete this
programme and could have organised seminars or workshops.
nS
tudent-led event: You may have arranged with your student colleagues to get
together to work through the cases.
We realise you may have difficulty doing some of the activities, especially those
related to practice. Think about working through these activities if you undertake
part-time or experiential work in a community pharmacy.
2
Please note: You are unable to attend CPPE-led events so, when the book refers to
these, please bear this in mind.
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Depression Book 1
Learning with CPPE

The Centre for Pharmacy Postgraduate Education (CPPE) offers a wide
range of learning opportunities in a variety of formats for pharmacy
professionals from all sectors of practice. We are funded by Health Education
England to offer continuing professional development for all pharmacists
and pharmacy technicians providing NHS services in England. For further
information about our learning portfolio, visit: www.cppe.ac.uk
1
We recognise that people have different levels of knowledge and not every
CPPE programme is suitable for every pharmacist or pharmacy technician.
We have created three categories of learning to cater for these differing
needs:

Core learning (limited expectation of prior knowledge)
Application of knowledge (assumes prior learning)

Supporting specialties (CPPE may not be the provider and will
3
direct you to other appropriate learning providers).
2
This is a
learning programme and assumes that you already have
some knowledge of the topic area.
Continuing professional development (CPD) You can use this

focal point programme to support your CPD. Consider what your
learning needs are in this area. You can record your CPD online by visiting:
www.collegeofpharmacy.com if you are a member of the BPSA or if
your school has subscribed to the CPD Online for Students service on
this website.
Programme guardians A programme guardian is a recognised expert in
an area relevant to the content of a learning programme. They will review the
programme every six months to ensure quality is maintained. We will post
any alterations or further supporting materials that are needed as an update
on our website. We recommend that you check for these updates if you are
using a programme more than six months after its initial publication date.
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We have developed focal point to give you short, clinically focused learning
sessions. It will help you learn with your colleagues and improve the services
you offer your patients. Each programme presents information and activities
that are relevant for pharmacy professionals working in primary care and in
the community.
Depression Book 1
About CPPE focal point programmes

Reference sources for all the books, articles, reports and websites mentioned
in the text can be found at the end of the programme. References are
indicated in the text by a superscript number (like this 3).
This book gets you started. It provides key information to help you meet the
learning objectives presented overleaf, but it also encourages you to identify
your own learning needs. It then challenges you to relate what you have
learnt to your own area of practice and professional development. We have
included practice points and talking points to stimulate your thinking. Make
sure you have undertaken these activities before your event, or, if you are
using this focal point for self-study, before commencing books 2 and 3.
Book 2 uses a case study and clinical vignettes to help you apply what you
have learnt and encourages you to make changes to improve your practice.
Book 3 contains some suggested answers to the learning activities in books 1
and 2.
A note about web links
Where we think it will be helpful we have provided the web links to take
you directly to an article or specific part of a website. However, we are also
aware that web links can change. The website: www.gov.uk/government
encompasses the Department of Health website, as well as the executive
agency, Public Health England. To search for any Department of Health
publication or information mentioned in this programme either visit the
gov.uk home page and enter the title into the search facility, or search via
Google or your preferred internet search provider.
If you have difficulty in accessing any other web links, please go to the
organisations home page and use appropriate key words to search for the
relevant item.
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Depression Book 1
About this focal point programme on

depression
In this programme we consider:
n the symptoms, diagnosis and classification of depression
n potential causes and risk factors
n evidence-based recommendations for the management of depression
n problems associated with the use of selective serotonin reuptake inhibitors
(SSRIs) and other antidepressants
n the burden of illness of depression.
Learning objectives
You can use our programmes to support you in building the evidence that
you need for the different competency frameworks that apply across your
career. These will include building evidence for your Foundation Practice
Framework (FPF), demonstrating development as your career progresses
with the Knowledge and Skills Framework (KSF) and supporting your
progression through the membership stages of the Faculty of the Royal
Pharmaceutical Society (RPS). As you work through the programme consider
which competencies you are meeting and the level at which you meet these.
What extra steps could you take to extend your learning in these key areas?
After completing this focal point programme, you should be able to:
n describe the symptoms of depression and the basis for the diagnosis of the
various severities of depression
n describe the evidence-based pharmacological and psychological
recommendations for the management of depression
n demonstrate an understanding of the impact depression has on patients
and those around them
n describe the risks and benefits of antidepressant treatment, in order to
support patients in optimising the use of their medicines
n describe where to signpost people with depression for further advice and
support
n apply a whole pharmacy team approach to supporting healthy lifestyle
messages for people living with depression
6
n discuss the condition, choice of medication, duration and withdrawal of

treatment with patients.
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Depression Book 1
Useful resources
We have selected some resources that you can use when developing improved
pharmacy services for people with depression.
Support for healthcare professionals
National Institute for Health and Care Excellence (NICE)
www.nice.org.uk
NICE clinical guideline 90: Depression in adults the treatment and management
of depression in adults. 2009.
NICE clinical guideline 91: Depression in adults with a chronic physical health
problem treatment and management. 2009.
British Association for Psychopharmacology www.bap.org.uk
Anderson IM et al. Evidence-based guidelines for treating depressive disorders with
antidepressants: a revision of the 2000 British Association for Psychopharmacology
guidelines. 2008.
Note: These guidelines are currently under review.
Patient, family and carer support
Choice and Medication www.choiceandmedication.org
This website provides information for people who use services, carers and
professionals. It provides answers to 30 of the most commonly asked questions
about 150 psychotropic medicines, as well as 15 of the most commonly
asked questions about 21 mental health conditions, all in easy-to-understand
language. All content is written by specialist mental health pharmacists.
You can normally access the website through a local NHS trust if it has a
subscription. Community pharmacists and independent healthcare providers
are also able to subscribe.
Depression Alliance www.depressionalliance.org
This website provides information about depression, its treatment and
recovery. There is also a very useful section on choosing an antidepressant:
http://whatyoushouldknow.depression-alliance.co.uk/choice/choosingantidepressants/
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Depression Book 1
Depression in adults (information for the public) www.nice.org.uk

NICE publishes each of its clinical guidelines in a version written especially for
the general public, patients and carers. This publication provides information
about what the public can expect from healthcare professionals when being
treated for depression.
NHS Choices www.nhs.uk
This website has been developed to help patients make positive choices
about their health. It provides facts about lifestyle decisions such as smoking,
drinking, reducing alcohol consumption, healthy eating and exercise, and
offers information about the practical aspects of finding and using NHS
services. It provides patients with explanations of nearly 800 treatments and
conditions. Pharmacy professionals can direct people to the NHS Choices
information on depression.
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To meet the learning objectives you will need to carry out the activities
listed in the table below. Weve given you this list now so that you can start
to plan your learning. Although it will only take you about two hours to
work through Book 1, feedback from other users suggests that it is useful
to plan your activities over a timescale that suits you - perhaps over several
days. Try to set yourself a realistic deadline for each task.
You will need to:
This will take
about:
Answer the Moving into focus
questions
5 minutes
List three learning needs
5 minutes
Read the whole book
60 minutes
Undertake the practice points
20 minutes
Depression Book 1
Checklist for planning
I will do this by:

(Insert date)
Make notes for the talking points 10 minutes

Work through your own
Directing change exercise
20 minutes
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Depression Book 1
Moving into focus

Consider the following questions. Use them to focus your thoughts and
stimulate your learning. Are you confident you know the answers?
1. What are the Whooley questions?
2. What are the differences between the presentation and treatment of

mild, moderate and severe depression?
3. What are the most common side-effects of SSRIs?
4.What are the most clinically significant drug interactions that involve
SSRIs?
5. How long do patients have to take antidepressants for before they start
working?
What are the implications of this?
6. How can you differentiate antidepressant discontinuation symptoms

from signs of addiction?
10
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Write down three things that you would like to gain from this focal point
programme. These will help you plan your own CPD entry. You will need to
tell others about them at the focal point event.
Depression Book 1
What do you want to learn?
1.
2.
3.
Now you have completed your reflection and planning for this focal point
programme, its time to undertake the background reading.
11
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Depression Book 1
Reading
1. Symptoms and diagnosis of depression
1.1 Epidemiology
The World Health Organisation estimates that by 2020, depression will be
the second leading cause of disability worldwide. At any one time 5 percent
of the population is suffering from depression. The lifetime risk is 12 percent
for men and 25 percent for women. At least a third of the population will
experience an episode of mild depression during their lifetime.1, 2 Almost 40
percent of people who meet the criteria for major depression do not go to
the doctor. Of those who do, only about 40 percent are correctly diagnosed.
Less than 10 percent of people correctly diagnosed are referred to secondary
mental health services, which means that the vast majority of people
diagnosed with depression are treated in the community by their general
practitioner (GP).1
Depression can occur in any person at any
age. The mean age for first onset is about 27
years old. It is twice as prevalent in women as
men and particularly common in women with
young children. About half of those who have
one episode of depression will have at least one
further episode, and about one in eight will
develop chronic depression.1, 2
Depression is often missed due to the presence
of anxiety, physical symptoms and its relationship with physical illnesses. A
person could present with mainly physical (somatic) symptoms, for example,
chronic pain, irritable bowel or recurrent headaches, and fail to mention
feeling depressed. The physical symptoms may appear to be linked to a preexisting physical illness. The GP may not suspect depression and treat the
physical symptoms only, leaving the underlying mood disorder unrecognised
and untreated.2 Depression often accompanies alcohol misuse.1 Social and
economic effects of depression include functional impairment, disability, lost
productivity and increased use of health services.
12
Many people with a chronic physical health problem such as diabetes,

chronic obstructive pulmonary disease or ischaemic heart disease also have
depressive illness. Depression creates a substantial burden of impairment
additional to that caused by the physical illness. The National Institute of
Health and Care Excellence (NICE) recognises this and has produced
specific guidance for this population.3
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Depression is an illness which is not always easy to define,

describe or identify. Two core features are persistent
low mood and lack of enjoyment (anhedonia).These
are usually accompanied by a range of other symptoms,
which may be psychological, physical, cognitive or
behavioural.
Notes
Depression Book 1
1.2 Symptoms2
Psychological symptoms
Low mood, anhedonia and negative thinking are the
key psychological symptoms. Anxiety is also extremely
common. Someone with depression may become
apathetic and withdrawn. There is often a diurnal
variation in mood: very low mood in the morning,
improving towards the evening, or the other way around.
A depressed person often sees the world and their place
in it in a very pessimistic light. They may have feelings of
low self-esteem and personal worthlessness. The world
may appear to them to be over-demanding and constantly
full of obstacles. Someone who is depressed will have
difficulty in expressing any optimism. When asked what
plans they have, a common reply is none. Instead, they
think about perceived past failings, which may assume
an inappropriate importance to them. It is common for a
depressed person to have an unnecessary sense of guilt,
blaming themselves for things with which they have no
connection.
Ultimately, a depressed person may have thoughts of
death. These usually come out of the blue, when they are
thinking about something totally unconnected. Thoughts
of death may become more serious, and comments
like life isnt worth living or Im just a burden or
they would be better off without me are common. A
depressed person may plan or even attempt suicide.
The above symptoms are sometimes described as the
depressive triad of hopelessness, worthlessness and guilt.4
2
13
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Depression Book 1
Physical symptoms
These are very common, particularly in older people with depression. They
include sleep disturbance, typically insomnia, which is accompanied by early
morning wakening. A depressed person may find it difficult to get to sleep
and may wake up between 4:00-5:00am. Much less common is hypersomnia,
where sleep is excessive. A depressed person generally feels physically tired
all the time, with no energy to do anything, even if they do not complain of
insomnia. Appetite may be poor and weight loss is common. Some depressed
people may comfort eat and actually gain weight. A depressed person
may display a number of other physical symptoms, sometimes referred to
as hypochondriasis, when no organic cause can be found. These include
gastrointestinal disturbance and pain.
Cognitive symptoms
Difficulty in concentrating is a common symptom and this impairs the
ability to function. Depressed people may complain of poor memory but
it is likely that this is due to their difficulty with concentration. This can
sometimes complicate the diagnosis in the elderly.
Behavioural symptoms
The most common behavioural changes seen in a person with depression are
agitation and psychomotor retardation. If agitated, the person may be nervy,
fidgety and find it difficult to remain calm. In psychomotor retardation they
may sit unmoving and unresponsive, or may respond to questions only
with monosyllables. Particularly noticeable can be the loss of associated
movements, a lack of body language, postural changes, gestures and
expressions that normally accompany conversation.
Self-neglect is common, sometimes to the point of starvation and even
refusal to take fluids. Such severe symptoms may be life-threatening if they
are not addressed rapidly, particularly in an elderly person.
This wide variety of symptoms may present in many ways, so depression
can appear very different from person to person. In addition, individual
symptoms may range from one extreme to another, sometimes making an
accurate diagnosis difficult.
Talking point A
Why are many people reluctant to seek help when they have symptoms
of depression?
14
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The presence of a low mood alone is not sufficient to

make a diagnosis of depression. The following should all
be taken into account:
n number of symptoms
Notes
Depression Book 1
1.3 Diagnosis and classification
n severity of symptoms
n degree of functional impairment
n duration and course of the illness.1
The table below shows the World Health Organisations
International Classification of Diseases (ICD-10) criteria
for the diagnosis of depression. It divides the symptoms
of depression into two groups, key and ancillary.5
Table 1. ICD-10 criteria for the diagnosis of the
various severities of depression
Key symptoms
Ancillary symptoms
Depressed mood
Reduced concentration and

attention
Loss of interest
and enjoyment
(anhedonia)
Reduced energy
leading to increased
fatigability and
diminished activity
Reduced self-esteem and

self-confidence
Ideas of guilt and
worthlessness
Bleak or pessimistic views
of the future
Ideas or acts of self-harm
or suicide
Disturbed sleep
Diminished appetite
15
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Depression Book 1
The severity of depression can be diagnosed based on the number of key

and ancillary symptoms a patient presents with.
n For mild depression a total of four symptoms must be present, of which
at least two must be key symptoms.
n Moderate depression is the diagnosis if at least five symptoms are
present (of which two must be key), with at least three (and preferably
four) other symptoms.
n Severe depression is where more than seven symptoms are
present, plus considerable distress and agitation unless psychomotor
retardation is a marked feature. Loss of self-esteem and feelings of
uselessness or guilt are common and suicide is a distinct danger.
Physical (somatic) symptoms are also likely to be present.
These symptoms must have been present for at least two weeks and
represent a change from previous (premorbid) functioning.
In its current clinical guidelines on the management of depression, NICE
uses the Diagnostic and statistical manual of mental disorders (DSM-IV)6
criteria for the diagnosis of depression, rather than ICD-10. This is because
the studies which support the guidelines recommendations all used DSMIV criteria. The criteria define nine symptom clusters, two of which are
classified as key (these are shown in bold in Table 2 below).
Table 2. DSM-IV criteria for the diagnosis of depression
1.
Depressed mood for most of the day, nearly every day
2.
Markedly diminished interest or pleasure in all, or almost all,

activities for most of the day, nearly every day

3.
Significant weight loss when not dieting, or weight gain (a change of

more than 5 percent body weight in a month) or a decrease or increase
in appetite nearly every day
4.
Insomnia or hypersomnia nearly every day
5.
Psychomotor agitation or retardation nearly every day
6.
Fatigue or loss of energy nearly every day
7.
Feelings of worthlessness or guilt nearly every day
8.
Diminished ability to concentrate, or indecisiveness nearly every day
9.
Recurrent thoughts of death, recurrent suicidal ideation, or a plan or
an attempt to commit suicide
16
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In May 2013 the fifth edition of the Diagnostic and

statistical manual of mental disorders (DSM-5) was
published with some changes to the section on depressive
disorders.7 These are likely to be reflected in the next
updated NICE guideline.
Notes
Depression Book 1
To make the diagnosis, five or more of these symptoms

must have been present for a period of at least two weeks
and there must be a change from previous functioning. At
least one must be a key symptom.
NICE guidance on the treatment of depression1 identifies

four severities of depression:
nS
ub-threshold fewer than five symptoms, at least
one key.
n Mild few, if any, symptoms in excess of the five
required to make the diagnosis. The symptoms result in
only minor functional impairment.
n Moderate symptoms or functional impairment are
between mild and severe.
n Severe most symptoms are present and the
symptoms markedly interfere with functioning. With or
without psychotic symptoms.
1.4 Screening for depression
There are many screening tests available to detect
depression. In primary care screening is particularly
appropriate and relatively easy to conduct in the following
patient groups:
n New patients a new patient registration check can
be performed by either a GP or practice nurse.
n Postnatal patients health visitors often use the
Edinburgh Postnatal Depression Scale (EPDS).8
n Those over 75 years of age depression is more
common in older people. The Royal College of General
Practitioners recommends the use of the Geriatric
Depression Scale (GDS).9
2
17
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Depression Book 1
NICE guidance1 and the British Association for Psychopharmacology10

guidelines recommend the following questions, sometimes called the
Whooley questions,11 to detect depression:
n During the past month, have you often been bothered by feeling down,
depressed or hopeless?
n During the past month, have you often been bothered by little interest or
pleasure in doing things?
If a patient answers yes to either of these questions, they may be
depressed. If they answer no to both questions, depression is highly
unlikely.
Other tools
The Patient Health Questionnaire (PHQ-9) is often used in primary
care to monitor the severity of depression and response to treatment. It
is not a screening tool but it can be used to make a tentative diagnosis of
depression. It scores each of the nine DSM-IV criteria as not at all (0) to
nearly every day (3).12
The General Health Questionnaire (GHQ-12) can be given to patients
when they register at a new GP surgery. This rating scale is commonly used
in primary care settings to help identify potentially depressed patients.13
The Cornell Scale for Depression in Dementia (CSDD) is a screening
tool for depression in older people with dementia who can communicate
basic needs.14
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Key symptoms of depression are:

n low mood most of the time
n lack of enjoyment.
Notes
Depression Book 1
Key points
Other ancillary symptoms must also be present for

an accurate diagnosis which is based on:
n number of symptoms
n severity of symptoms
n degree of functional impairment
n duration and course of the illness.
NICE identifies four severities of depression:
n Sub-threshold
n Mild
n Moderate
n Severe
Practice point 1
What symptoms of depression do you most commonly see in your practice?
Why does depression not always get recognised?
19
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Depression Book 1
2. Causes and risk factors

2.1 Causes of depression
Depression can be caused by psychological, genetic and biological factors.
Certain significant life experiences can increase the risk of depression.
These could include abuse, separation, childhood neglect, an unusually
high number of life events (for example, bereavement, unemployment),
continuing stressors such as work or relationship problems and the absence
of a confiding relationship. However, many people experience such things
without ever becoming depressed, while others who have no obvious
precipitating factor experience depressive episodes. This suggests individual
differences in susceptibility, which may include genetic and biological
features.
Family and twin studies have provided strong evidence of a genetic basis
for susceptibility to depression. This may involve genes concerned with
the function of neurotransmitters and receptors, or the way in which an
individual perceives a certain event as a stressor.2
Cortisol and monoamines are likely biological candidates. Depression
can lead to higher cortisol levels and larger adrenal glands. When the
depression is successfully treated the adrenal glands shrink back to normal
and cortisol levels fall. The monoamine
hypothesis proposes a functional deficit
of monoamine transmission in the central
nervous system, involving deficits of
the neurotransmitters noradrenaline,
serotonin (5-HT) and dopamine in the
synaptic cleft. The introduction of the
antidepressant, agomelatine, has suggested
additional involvement of sleep-wake
cycle abnormalities. Evidence for the monoamine hypothesis is incomplete.2
It is important to remember that some prescribed medicines may cause
depressive symptoms, as can sudden withdrawal from certain medicines and
substance misuse and abuse.
Many factors can trigger depression. Psychological and biological factors
cannot be completely separated because psychological changes can affect
brain biochemistry, especially through changes in cortisol secretion.
Conversely, altered brain biochemistry can affect how a person reacts to
external events.
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Depression often presents with an overlay of anxiety and

it can be difficult to separate the two. If symptoms of both
depression and anxiety are present with such an equal
intensity that a clear cut diagnosis is not possible, the term
mixed anxiety and depressive state is used. Many
antidepressants have proven efficacy in some anxiety
disorders and should therefore address both types of
symptoms.
Notes
Depression Book 1
2.2 Differential diagnosis2
Mood disturbance may also be due to the effect of a

physical or organic illness. This should be eliminated
before making a firm diagnosis of depression. Such
illnesses may include:
n Hypothyroidism
n Stroke
n Multiple sclerosis
n Occult carcinoma
n Metabolic and endocrine disorders (eg, Cushings

disease)
n Viral infections
n Anaemia
n Dementia
The prevalence of depression is much higher in
people with certain physical illnesses than in the
general population (see Section 1.1). The symptoms of
depression may go unrecognised, with consequent underdiagnosis and under-treatment. Co-morbid depression
is associated with increased morbidity, poorer function,
increased healthcare costs and increased mortality.
Successful treatment can result in improved quality of
life as well as improved function, mortality and overall
outcome in the physical disorder. NICE guidance
has given special consideration to the management
of depression in adults with a chronic physical health
problem.3
2
21
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Depression Book 1
If a person does not appear to respond to pharmacological interventions as

expected, but is known to have been taking their medicines as prescribed,
bipolar depression should be considered. Bipolar depression occurs
cyclically with hypomania or mania in the context of bipolar affective
disorder. A person with bipolar depression shows reduced responsiveness to
conventional antidepressants, some of which may, on rare occasions, cause
a switch of mood to hypomania or even mania.2 A history of hypomania
or a family history of bipolar disorder will add weight to the diagnosis of
bipolar depression, which requires a different treatment strategy and possibly
specialist referral.
2.3 Risk factors for depression2
Depression should always be considered in someone who:
n has had previous episodes of depression
n has unexplained physical symptoms
n has experienced recent life events, eg, a birth, bereavement, marriage,

redundancy, long-term unemployment, divorce, pregnancy, termination or
miscarriage
n has coronary heart disease, for example, post-myocardial infarction
n has a family history of depressive illness or bipolar disorder
n has a chronic physical illness or disability
n has a history of stroke
n has a history of alcohol/substance misuse or abuse

n is socially isolated or deprived
n suffered physical/sexual abuse, neglect or separation during childhood

n is taking or has recently stopped taking certain prescribed medicines
n lacks a close confiding relationship.
Key points
n Depression can be triggered by psychological, genetic or biological
factors.
n Many physical illnesses, as well as the medicines used to treat them,
are associated with depression.
n If a patient doesnt respond to antidepressant treatment, bipolar
depression should be considered.
22
n Depression should always be considered in a person with any risk

factors.
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Which medicines or groups of medicines are

associated with causing depressive symptoms?
Notes
Depression Book 1
Practice point 2
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Depression Book 1
3. Treatment
The following table shows the NICE recommendations for the management
of the various severities of depression.1
Table 3. The stepped-care model
Presentation of depression
Recommended interventions
Step 1
All known and suspected

presentations of depression
Assessment, support,
psycho-education, active
monitoring and referral for further
assessment and interventions.
Step 2
Mild to moderate depression
Low-intensity psychological
and psychosocial interventions,
medication and referral for further
assessment and interventions.
(plus persistent sub-threshold

depressive symptoms)
Step 3
Moderate to severe
depression
(plus persistent sub-threshold
depressive symptoms or mild
to moderate depression with
inadequate response to initial
interventions)
Step 4
Severe depression
(and complex depression,
which is depression that shows
inadequate response to multiple
treatments, is complicated by
psychotic symptoms and/or
is associated with significant
psychiatric co-morbidity or
psychosocial factors)
Medication, high-intensity
psychological interventions,
combined treatments, and referral
for further assessment and
interventions.
Collaborative care is additionally
recommended if the person also
has a chronic physical health
problem and associated functional
impairment.
Medication, high-intensity
psychological interventions,
electroconvulsive therapy, crisis
intervention, combined treatments,
multiprofessional and in-patient
care.
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Effective treatment for depression should return the

person to their premorbid state. They need to be
completely free from depressive symptoms (feeling
better is not good enough) because residual symptoms
are predictors of relapse, suicide and functional
impairment. Effective treatment must be provided early
to reduce mortality and risk, normal functioning must be
restored and the risk of recurrence prevented or reduced.
Notes
Depression Book 1
3.1 Pharmacological management
Treatment can be divided into three phases:

n Acute
n Continuation
n Prophylaxis
Acute phase
About three quarters of people diagnosed with depression
will respond to acute treatment with an antidepressant,
providing a minimum effective dose is maintained for an
adequate period of time. This phase involves achieving
an effective dose and maintaining it for at least six weeks.
Antidepressants are now thought to start to work within
the first two weeks of treatment.15
Continuation phase
Following remission in the acute phase of treatment, the

antidepressant should be continued at the effective dose
for at least a further six months. This reduces the risk of
recurrence, and the risk is even less if treatment continues
for a year. Relapse and recurrence are often confused. A
relapse is a re-emergence of symptoms occurring within
a single episode of depression. Typically, a patient takes
an antidepressant, the symptoms ease, the patient stops
taking the antidepressant prematurely and the symptoms
return. A relapse may also occur during treatment.
Recurrence is when a new episode of depression occurs,
following recovery from a previous episode and after
a long symptom-free period.1, 2 A patient can normally
be considered recovered following six months of being
symptom free, and treatment may be gradually withdrawn.
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Prophylactic phase
If a person has a history of recurrent episodes, treatment should continue
after the continuation phase. The aim of this is to prevent another episode
occurring in the future. NICE recommends at least two years of treatment
for those with recurrent depression or who are at significant risk of
recurrence.1 Treatment for life may be necessary for some. During such
chronic treatment it is important that their physical health is monitored. Any
deterioration may require a change of antidepressant.
NICE states that antidepressants should not be routinely prescribed for those
with sub-threshold or mild depression as the risks outweigh the benefits.1
Antidepressants should be reserved for people:
n with moderate to severe depression
n with a history of moderate or severe depression
n who initially present with sub-threshold depressive symptoms that have

been present for at least two years
n with sub-threshold depressive symptoms or mild depression which persist
after other interventions have been tried.
See Table 3 at the start of Section 3 for more details.
Choice of treatment
A generic SSRI should normally be prescribed first-line. This should be
reviewed after two weeks, then every two to four weeks for the first three
months and then at longer intervals following a good response. If there
is no improvement within the first two to four weeks adherence should
be checked. If there is still an inadequate response after three to four
weeks, despite good adherence, the following next-step treatments1 are
recommended:
n Increase the dose of the SSRI, if side-effects permit, according to
the summary of product characteristics. However, only sertraline has
demonstrated a dose response curve.1
26
n Switch to a different SSRI or a newer generation antidepressant, which

may be better tolerated. Subsequently, an antidepressant from a different
class can be used but may be less well tolerated (see Section 3.3 for more
information on other antidepressants). Open studies have shown that 50
percent of patients who do not respond to the first antidepressant they are
prescribed are likely to respond to a second antidepressant, regardless of
whether it is from the same class or not.1
09/04/2015 14:53
Notes
Depression Book 1
n Combine antidepressants. By combining

antidepressants it may be possible to target specific
receptors to achieve serotonergic and noradrenergic
effects. Combinations of serotonergic agents with
different modes of action may increase 5-HT
transmission more than if either are used alone.
However, this can increase the chances of side-effects
and cost. Potential interactions with other co-prescribed
medicines must also be considered. Although there is
some evidence of improved efficacy with combined
antidepressants, the evidence base is poor.1, 16 The best
evidence is for the combination of an SSRI with either
mirtazapine or mianserin. Only very limited evidence
exists for the more commonly seen combination of
venlafaxine with mirtazapine.16
n Augment with lithium or an atypical
antipsychotic, such as aripiprazole, olanzapine,
quetiapine or risperidone. Levothyroxine, antiepileptic
agents, buspirone or pindolol should not be routinely
prescribed as augmentation agents because there is no
evidence to support such use.1
3.2 Problems associated with SSRIs
Side-effects
While SSRIs are generally better tolerated than other
antidepressants they can cause side-effects. Many of these
are transient. Anxiety symptoms may be exacerbated at
the start of treatment but these will wear off in time and
can be minimised with a starting dose at the lower end
of the recommended range. In the long term SSRIs are
anxiolytic. SSRIs are not usually sedative and should be
taken in the morning. Gastrointestinal side-effects such
as nausea, vomiting and diarrhoea may be a problem
for some and Parkinsonian motor symptoms, akathisia
(a feeling of restlessness or anxiety) and bruxism (teeth
grinding) have occasionally been reported.
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Depression Book 1
Sexual dysfunction is not uncommon and loss of libido may also occur. It is
common for people who have depression to experience loss of libido, but if it
persists when all other symptoms of depression have lifted, it is likely to be a
side-effect of the antidepressant. These are important factors in maintaining
adherence for some people, particularly since sexual dysfunction is not
usually a transient side-effect of treatment. If sexual dysfunction continues
to be a problem then a switch to another antidepressant which does not raise
serotonin levels (such as mirtazapine or agomelatine) may be indicated.
Mirtazapine is sedative and may be useful if sleep disturbance is a problem,
but it also causes weight gain.
SSRIs are generally safer in overdose than many other antidepressants but
citalopram and, to a lesser extent, escitalopram have been associated with
prolongation of the QT interval. This has led to changes to the summary of
product characteristics regarding dosage and use in situations where the QT
interval may already be compromised.17
SSRIs have been linked with an increased risk of abnormal bleeding.18, 19 It is
thought that this is as a result of SSRIs decreasing the amount of serotonin
in platelets, which would normally potentiate aggregation. NICE cautions
strongly against the combined use of SSRIs with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) and recommends that when
such co-prescribing is unavoidable additional cover with a proton pump
inhibitor should be provided.3
Drug interactions
Most SSRIs inhibit certain hepatic microsomal cytochrome P450
enzymes but they vary in the potency with which they do this. Citalopram,
escitalopram, fluvoxamine and sertraline are relatively weak CYP-2D6
enzyme inhibitors at low dose. Paroxetine and fluoxetine are stronger.
Most problems occur when SSRIs are prescribed concomitantly with
medicines which have a narrow therapeutic index, where slight changes in
plasma concentration may have significant clinical implications. SSRIs are
protein bound so the potential for displacement of other protein-bound
medicines, such as warfarin, can lead to reduced coagulation. This, together
with the risk of increased bleeding, has led to the recommendation that
SSRIs should not normally be offered to people on warfarin or heparin.1
Pharmacodynamic interactions may occur with aspirin and other NSAIDs,
leading to an increased risk of abnormal bleeding, and with triptans, leading
to an increased risk of serotonin syndrome (see Section 3.4).
28
Appendix 16 of NICE clinical guideline 91 contains a very useful table of

interactions with SSRIs.3
09/04/2015 14:53
Mirtazapine, a noradrenaline and specific serotonin

antidepressant (NASSA), is an alpha2-adrenoreceptor
antagonist. Unlike SSRIs it enhances both serotonergic and
noradrenergic transmission in the central nervous system,
but does not have a direct effect on serotonin levels in the
synaptic cleft. NICE reports it to be as effective as other
antidepressants, with a possible advantage in terms of
reducing those side-effects that may affect adherence (such
as sexual dysfunction).1 Adverse effects include sedation
(which may be useful in those with sleep disturbances),
constipation, dry mouth and weight gain.
Notes
Depression Book 1
3.3 Other antidepressants
Agomelatine, through its serotonergic 5-HT2C receptor

antagonist activity, causes release of both noradrenaline
and dopamine in the prefrontal cortex, an area of the
brain involved in mood, anxiety and cognition. This,
together with its agonist action at melatonin receptors
(MT1 and MT2), is thought to restore disturbed
circadian rhythms, such as the sleep-wake cycle in those
suffering from depression, as well as contributing to an
antidepressant effect.
Agomelatine has no influence on extracellular serotonin levels
nor on monoamine reuptake. Additionally, unlike most other
antidepressants, there is no significant activity at any other
receptor either centrally or peripherally. This may explain its
favourable tolerability profile with several potential clinical
advantages over other antidepressants, in particular the fact
that it does not cause weight gain or sexual dysfunction.20
Venlafaxine and duloxetine are dual reuptake

inhibitors, improving both serotonergic and
noradrenergic transmission. They are known as serotoninnoradrenaline reuptake inhibitors (SNRIs). Unlike
tricyclic antidepressants (TCAs) they are not sedative
and have no anticholinergic effects. NICE found no
clinically important advantages for venlafaxine and
duloxetine over the SSRIs, but it states that patients
are more likely to stop treatment early when prescribed
these SNRIs due to side-effects.1 However, in practice
venlafaxine is often used as a treatment option for those
who have failed to respond to initial antidepressants.
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Tricyclic antidepressants, such as amitriptyline, imipramine and

lofepramine inhibit the reuptake of both noradrenaline and serotonin
from the synaptic cleft into the pre-synaptic neurone. This increases
the availability of these transmitters, and enhances noradrenergic and
serotonergic transmission. However, they also impact on a wide range of
other receptors, resulting in many intolerable side-effects such as sedation,
memory problems, confusion, dry mouth, blurred vision, constipation,
urinary retention and hypotension.
TCAs may be cardiotoxic even at therapeutic doses, and with the exception
of lofepramine are highly toxic in overdose. They have a quinidine-like
effect on the heart. This can lead to conduction deficits, which may result
in arrhythmias and fatal heart block. They are best avoided in patients with
cardiac conduction disorders, and are contraindicated in patients with recent
myocardial infarction or first-degree heart block. NICE states that dosulepin
should no longer be prescribed.1
Monoamine oxidase inhibitors (MAOIs) should only be used under
specialist supervision for the treatment of resistant or atypical depression.
They are not indicated as first-line treatments, but can be useful when severe
anxiety or obsessional thoughts are prominent features of a major depressive
illness. They work by combining irreversibly with monoamine oxidase,
which is the enzyme responsible for the breakdown of the monoamine
neurotransmitters, and in this way are thought to improve central
neurotransmission by increasing the availability of those transmitters in the
synaptic cleft.
They have a similar side-effect profile to the TCAs but, in addition, have
the potential for possibly life-threatening interactions with other commonly
used medicines, including TCAs, as well as foods that contain tyrosine
and tyramine. This interaction with foodstuffs is known as the cheese
reaction and can result in a hypertensive crisis. Patients must be warned
about the foods and medicines to avoid and encouraged to carry a warning
card at all times. When switching from an MAOI to an antidepressant
from a different group, a washout period of at least two weeks should be
observed, which must be extended to three weeks if starting clomipramine
or imipramine. This is to allow new enzymes to be synthesised. Interacting
foods and medicines should be avoided during this time. An MAOI should
not be started until at least seven to fourteen days after a tricyclic or related
antidepressant has been stopped, and after three weeks in the case of
clomipramine or imipramine.
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Notes
Depression Book 1
Moclobemide is a competitive (reversible) inhibitor of

monoamine oxidase. It is displaced by large amounts of
ingested or released endogenous amines, and therefore
only causes minimal potentiation of the hypertensive
effect of sympathomimetic amines found in food or as a
result of co-prescribed medicines. This means that there
is little risk of a potentially fatal hypertensive crisis, and
the need for dietary caution or the avoidance of other
medicines is reduced.
3.4 Serotonin syndrome
Serotonin syndrome is a potential risk with any
medicine which increases serotonergic transmission,
especially high-dose SSRIs, and when antidepressants
are used in combination or with lithium. It is caused by
hyperstimulation of the serotonin system and is thought
to be grossly under-reported. It is usually mild and can
be managed by dosage reduction, or medicine withdrawal
plus benzodiazepines. However, in its most severe form
it requires major supportive measures as it can result in
multiple organ failure and death. It is characterised by the
following:
n Agitation, restlessness
n Tremor
n Sweating, fever, shivering
n Diarrhoea, nausea, vomiting

n Hyperreflexia, myoclonus
n Poor co-ordination, confusion, hypomania

n Hypertension
n Tachycardia
n Convulsions
Onset is usually within a few hours of medicine or dosage
changes. Recurrent, mild symptoms may occur for weeks
before a full blown syndrome appears. Symptoms usually
resolve within 24 hours of withdrawal.
2
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3.5 Antidepressant discontinuation symptoms

All classes of antidepressants can cause discontinuation symptoms, but they
are more commonly associated with those with shorter elimination halflives. Of the SSRIs, reports of discontinuation symptoms are most common
with paroxetine, and least common with fluoxetine.21 Discontinuation
symptoms may impair a patients quality of life. An incorrect diagnosis of
discontinuation symptoms may have serious consequences, such as:
n the patient misinterpreting them as symptoms of a relapse, which may
result in treatment continuing longer than needed
n unnecessary clinical investigations may be ordered
n unnecessary treatments may be prescribed to manage the symptoms
n having a negative influence on adherence, possibly adding to a patients

fears that antidepressants are addictive.
Symptoms usually occur within 72 hours of sudden antidepressant
discontinuation or rapid dose reduction. They have not been reported in
patients who have been taking antidepressants for less than five to six weeks.
The most common discontinuation symptoms reported with SSRIs are:
n Dizziness, light headedness, vertigo, ataxia
n Nausea, vomiting, diarrhoea
n Lethargy, headache, tremor, sweating, anorexia
n Paraesthesia, numbness, electric shock like sensations

n Irritability, anxiety, agitation, low mood
They are usually transient and most cases resolve spontaneously within a few
days. If severe and not self-limiting, such symptoms almost always respond if
the patient restarts the antidepressants.
Management of discontinuation symptoms
To reduce the risk, antidepressants should always be withdrawn gradually
over a period of at least a month. The majority of patients who experience
discontinuation symptoms require no more than an explanation and
reassurance.
Many patients stop their treatment prematurely because they fear addiction,
dependence or tolerance. It is important to distinguish discontinuation
symptoms from the withdrawal syndrome seen on stopping a drug of
dependence. Antidepressant use does not result in craving, tolerance or
primacy, three key features of addiction to drugs of dependence.
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Recommended
interventions for
the management
of depression also
include psychological
therapies, either alone
or in combination with
antidepressants.
Notes
Depression Book 1
3.6 Psychological
interventions
Several psychological
approaches are
possible, such
as psychosocial
support, counselling
or psychotherapy
including cognitive
behavioural therapy (CBT). In general, psychological
treatments alone seem most effective in milder forms of
depression, but in combination with an antidepressant
they have a synergistic effect at the more severe end of the
spectrum. The decision about what type of treatment is
offered depends on several factors, including:
n patient preference
n the severity of the depression

n duration of symptoms
n whether the person has had treatment before and how

helpful it was
n potential side-effects of treatments
n availability of psychological therapies.

Low intensity psychological and psychosocial
interventions should be offered to those with:
n persistent sub-threshold depressive symptoms
n mild to moderate depression, so long as they do not

have a chronic physical health problem.
Such interventions include guided self-help, computerised

CBT, group CBT and physical activity.1
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High intensity psychological interventions, either alone or in combination

with antidepressants, should be offered to those with:
n persistent sub-threshold depressive symptoms
n mild to moderate depression which has responded inadequately to initial

interventions
n those with moderate or severe depression.1
Such interventions include individual CBT, interpersonal therapy,
behavioural activation and behavioural couples therapy for those without a
chronic physical health problem.1 Group-based CBT, individual CBT and
couples therapy are recommended for those with a chronic physical health
problem.3
3.7 Other strategies to manage depression
St Johns wort
St Johns wort has been shown to have mild antidepressant properties,
thought to be due to serotonin, dopamine and noradrenaline reuptake
inhibition and a weak monoamine-oxidase inhibitory effect.22 It is a popular
public misconception that such herbal remedies are natural and therefore
safe. However, they are unlikely to be pure and may be contaminated, with
the level of active ingredients varying between preparations.
There is mounting evidence of
significant interaction between St
Johns wort and other medicines,
such as oral contraceptives,
anticonvulsants, theophylline
and ciclosporin, due to hepatic
enzyme induction. Also, when
taken in combination with other
antidepressants, especially
SSRIs, there have been reports of
serotonin syndrome. The Committee on the Safety of Medicines has issued a
cautionary warning on the use of St Johns wort.23 Although there is evidence
that it may be of benefit in mild or moderate depression, NICE recommends
that it should not be considered for people with depression because of
the uncertainty about appropriate doses, persistence of effect, variation
in the nature of preparations and potential serious interactions with other
medicines.1
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Electroconvulsive therapy (ECT) is an effective treatment

usually reserved for those with severe depression,
particularly depression with psychomotor retardation,
who have stopped eating or, in extreme cases, stopped
drinking. Under such circumstances ECT is sometimes
a preferred intervention for the elderly. It is also used
to treat depression which has not responded to other
strategies. However, it is viewed with apprehension by
many. It involves inducing a seizure by passing an electric
shock through electrodes placed on the head. The effects
of ECT are rarely long-lasting so antidepressants and/or
lithium are usually prescribed following ECT to maintain
the response. A course usually consists of six to twelve
treatments, given twice a week over three to six weeks.1
Notes
Depression Book 1
Electroconvulsive therapy
3.8 NICE quality standard

NICE has produced a quality standard that defines
clinical best practice for the management of depression in
adults.24 This quality standard covers the assessment and
clinical management of adults with depressive symptoms
including those with a co-morbid chronic physical health
problem. It describes markers of high-quality, costeffective care that, when delivered collectively, should
contribute to improving the effectiveness, safety and
experience of care for people with depression.
Key points
nP
sychosocial interventions should be offered instead
of antidepressants for mild depression.
nP
sychological and pharmacological interventions are
recommended for moderate and severe depression.
nA
n SSRI is the first-line antidepressant for moderate
and severe depression.
nS
ide-effects of SSRIs are usually transient.
nP
sychological interventions may be used alone or in
combination with an antidepressant if the previous
response to an antidepressant alone has been
inadequate.
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n Patients should be informed about discontinuation symptoms.
n SSRIs should not be prescribed with aspirin or other NSAIDs unless

a proton pump inhibitor is also prescribed.
n SSRIs are contraindicated with anticoagulants, and should not be
prescribed with triptans.
n St Johns wort is not recommended for the treatment of depression.
Practice point 3
What local and national self-help groups and resources are available for
someone living with depression?
4. Suicide 1, 25
Suicide is very difficult to predict, but if a patient mentions thoughts or plans
of self-harm they should always be taken seriously and referred to someone
qualified to help them. It does no harm to ask a depressed person if they
have thoughts of harming themselves. It is a myth that such questions serve
to put these thoughts into their heads. A clinician would normally ask a
patient the following questions sensitively and in private:
n How do you feel about the future?
n Have you ever felt that life isnt worth going on with?
n Have you ever had thoughts about taking your own life?
n Have you made any definite plans to do so and, if so, what are these plans?
How recently have you considered carrying them out?
n What has actually stopped you from harming yourself so far?
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Notes
Depression Book 1
If a person expresses thoughts of self-harm to a member of

the pharmacy team it is vital that they are referred to and
followed up by a person skilled in this area, such as their GP
or a community mental health nurse. The following people
are particularly at risk of suicide or self-harm:
n recently widowed men
n young men
n those under 30 who have been prescribed an SSRI
antidepressant within the last week.
There are two potentially conflicting claims concerning
the association of antidepressants with suicide:
n Antidepressants reduce suicide rates. It has been
demonstrated that treatment with antidepressants is
associated with a rapid and significant reduction in
suicidal behaviour.26, 27
n Antidepressants increase the risk of suicide in
certain patients. There is evidence that in some
people, especially men under the age of 30, certain
antidepressants, particularly SSRIs, can increase
impulsivity.28
The evidence available is conflicting. Following the
warning that antidepressants may increase the risk of
suicide, a study in Sweden considered trends in the
use of antidepressants among 845 people aged 10-19
years who committed suicide. The study found that
suicide in this age group increased by 60.5 percent,
from 49 in 2003 to 69 in 2008; the increase occurred
among those individuals who had not been treated with
antidepressants. The authors concluded that this provides
support for the hypothesis that the warning of an
increased risk of suicide in young people, contrary to its
intention, may have increased suicides in this age group
by leaving a number of suicidal young people without
treatment with antidepressants.29
If a suicide risk exists, an antidepressant that is safe in

overdose must be chosen. Alternatively, only a small
supply should be dispensed weekly prescriptions may
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Depression Book 1
be considered. Previous attempts at self-harm increase the risk of suicide

and feelings of hopelessness correlate with this risk. Whatever treatment
is prescribed, those considered to be at risk of self-harm should be closely
monitored for the first few weeks of treatment. NICE makes the following
recommendation:
Those at risk of suicide or anyone younger than 30 should normally be seen one
week after starting an antidepressant and frequently thereafter as appropriate,
until the risk is no longer considered clinically important, because of the potential
increase in suicidal thoughts in the early stages of treatment in this group. 1
5. Living with depression30
A person with depression can find simple, day-to-day tasks impossible. It can
take a huge amount of strength and motivation to manage the most basic of
activities, like getting out of bed and leaving the house. Things others take for
granted, like speaking to friends or making a cup of tea, can be exhausting
and many worry about not being able to function as they used to. They may
no longer be able to face going to work, school or college or meeting up with
friends socially. When depression takes hold some people find themselves
overwhelmed by emotions, while others feel cut off from them. They find
it hard to explain their thoughts and feelings to others. This can make
relationships difficult, which can lead to isolation and loneliness.
In mental illness, recovery does not always refer to the process of complete
recovery in the way that people may recover from a physical health problem.
For many the concept of recovery is about staying in control of their life
despite experiencing a mental illness. In the depths of depression recovery
can seem unimaginable, which is why encouraging someone to get help isnt
always straightforward. Most people with depression will get better with
the right treatment and support. For some it takes months, for others years.
Periods of stress or change can be difficult, resulting in an exacerbation of
symptoms. For many, recovery is about being able to manage depression in
the long term, so they are more likely to be able to prevent their symptoms
from recurring or stop them becoming unmanageable if they do.21
In the treatment of depression, good adherence is vital for a good outcome.
It has been shown that patient education can aid adherence. Patients fears
must be addressed from the beginning, and the following information should
be discussed with them:
n Depression is a treatable illness.
n Depression is a disorder with a physical basis which is easily treated.
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n Depression is common, affecting a quarter of the

population at some time in their lives.
n Sleep disturbances can be part of a depressive illness.
Notes
Depression Book 1
n There should be no fear or stigma attached to

admitting depressive symptoms.
n Maintain regular sleeping habits if possible.

n Avoid daytime naps.
n Avoid caffeine in the evenings.
n Avoid hypnotics except as short-term aids to sleep

at the start of treatment, if required.
n Antidepressants are effective in the treatment of
depression; they are not tranquillisers and there is no
risk of addiction or dependence.
n Antidepressants need to be taken every day, and
should be taken at an effective dose for at least six
months once the symptoms of depression have
resolved, and sometimes much longer, to prevent
recurrence.
n Although some patients may see some improvement
from week one, the full effect of antidepressants may
take two to four weeks and sometimes longer.
n Side-effects may occur but many are transient and will
disappear after a week or two.
n Antidepressants should not be stopped suddenly
because of forgetfulness, in a deliberate attempt to
restore sexual function or for any other reason, as this
may result in the occurrence of unpleasant symptoms.
n Once the treatment is completed, the antidepressant
should be withdrawn gradually over a period of at least
a month. If discontinuation symptoms do occur and
are severe and persistent, the antidepressant should be
restarted and tapered more slowly than before.
Talking point B
2
How can you encourage good adherence to

antidepressant treatment in a person with depression,
in order to achieve the best outcome for them?
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Depression Book 1
Key points
n Diagnosis of depression should include an assessment of the severity
and duration of symptoms, together with degree of functional
impairment.
n Patients should be reviewed on a regular and frequent basis and their
progress recorded in their notes.
n People with depression with or without a co-morbid chronic physical
health problem should be treated according to the relevant clinical
guideline.
n Antidepressant treatment should continue for a minimum of six months
from remission or significantly longer if the risk of recurrence is high.
n An informed patient is more likely to be engaged with their care and
make better choices.
Practice point 4
The cost to the individual and to society of untreated or inadequately
treated depression is enormous. Effective treatment not only relieves
human suffering but also helps restore function, reduce disability and
lower costs. The burden imposed on family, carers and society as a
whole is reduced if depression is recognised early and treated promptly
and effectively.
How can a member of the pharmacy team assist with this?
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n Depression is a treatable illness and should not be

associated with any stigma.
n People with symptoms of depression should be
encouraged to seek help.
n Pharmacological and psychological interventions have
been shown to be effective in the management of
depression both alone and in combination.1
n Psychosocial interventions are recommended for mild
depression while SSRIs are first-line treatment for
moderate to severe depression.1
n SSRIs should not be co-prescribed with aspirin or
other NSAIDs unless cover with a proton pump
inhibitor is also provided, due to the increased risk of
abnormal bleeding. For the same reason SSRIs are
contraindicated with anticoagulants such as warfarin.1
n SSRIs should not be prescribed with triptans due to
the increased risk of serotonin syndrome.1
Notes
Depression Book 1
Summary of background
reading
In order to get the best from the focal point event that
you attend, you should now complete the Directing
change exercise on the next page.
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Depression Book 1
Directing change
Here we give you the opportunity to reflect and consider how you could
improve your practice in this area.
Think about patients you see who have depression. How can the pharmacy
team support these people better?
Think about your own role within pharmacy.
n Do you undertake medicines use reviews (MURs)/medication reviews with
people who have depression? Can you target MURs/medication reviews for
the next few weeks to these people, to investigate their medication issues
and try to help them with your newly-updated clinical skills?
n If you do not undertake MURs/medication reviews, are you aware of local
support to which you can signpost people with depression?
What else can you do to support people with depression?
Take some time to make a few notes, and be prepared to discuss them with
colleagues at the event. You will then be able to build on your own ideas and
put your plans into action the following day in your pharmacy.
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At this point in the learning programme you will have carried out the
following.
Action
I completed this on:
Depression Book 1
Checklist for action
I have answered the Moving into

focus questions
I have listed three learning needs
I have read the whole book
I have undertaken the practice points
I have made notes for the talking points
ready to share at the event
I have worked through the Directing
change exercise
Signed:
Date:
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Depression Book 1
References
1. National Collaborating Centre for Mental Health. Depression: The NICE guideline on the
treatment and management of depression in adults (updated edition). The British Psychological
Society and The Royal College of Psychiatrists. 2010. www.nice.org.uk
2. Cowen P, Harrison P, Burns T. Shorter Oxford textbook of psychiatry. Sixth edition. Oxford:
Oxford University Press; 2012.
3. National Collaborating Centre for Mental Health. Depression in adults with a chronic physical
health problem: The NICE guideline on treatment and management. The British Psychological
4. Beck AT, Rush AJ, Shaw BF, Emery G. Cognitive therapy of depression. New York: Guilford
Press; 1979.
5. World Health Organisation. Classifications: International Classification of Diseases (ICD).
www.who.int/classifications/icd/en
6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders
DSM-IV. Fourth edition. Virginia: American Psychiatric Association; 1994.
DSM-5. Virginia: American Psychiatric Association; 2013.
8. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the
10-item Edinburgh Postnatal Depression Scale. The British Journal of Psychiatry
1987;150: 782-786. www.fresno.ucsf.edu/pediatrics/downloads/edinburghscale.pdf
9. Greenberg SA. The Geriatric Depression Scale (GDS). Try This 2012;(4).
http://consultgerirn.org/uploads/File/trythis/try_this_4.pdf
10. Anderson IM et al. Evidence-based guidelines for treating depressive disorders with
antidepressants: a revision of the 2000 British Association for Psychopharmacology
guidelines. British Association for Psychopharmacology. 2008. www.bap.org.uk
11. Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression.
Two questions are as good as many. Journal of General Internal Medicine 1997;12(7): 439-445.
12. Patient information Publications. Patient Health Questionnaire (PHQ-9).
www.patient.co.uk/doctor/patient-health-questionnaire-phq-9
13. Hankins M. The reliability of the twelve-item general health questionnaire (GHQ-12) under
realistic assumptions. BMC Public Health 2008;8: 355.
www.biomedcentral.com/1471-2458/8/355
14. The Royal Australian College of General Practitioners. Cornell Scale for Depression in
Dementia. www.racgp.org.au/your-practice/guidelines/silverbook/tools/cornell-scalefor-depression-in-dementia/
15. Taylor MJ, Freemantle N, Geddes JR, Bhagwagar Z. Early onset of selective serotonin
reuptake inhibitor antidepressant action systematic review and meta-analysis. Archives of
General Psychiatry 2006;63(11): 12171223.
44
16. Feetam C. Are two antidepressants always better than one? Progress in Neurology and
Psychiatry 2012;16(3): 5-8. www.progressnp.com
09/04/2015 14:54
Depression Book 1
17. Medicines and Healthcare products Regulatory Agency. Citalopram and escitalopram:
QT interval prolongation new maximum daily dose restrictions (including in elderly
patients), contraindications, and warnings. Drug Safety Update 2011;5(5).
www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON137769
18. Dalton SO et al. Use of selective serotonin reuptake inhibitors and risk of upper
gastrointestinal tract bleeding a population-based cohort study. Archives of Internal
Medicine 2003;163(1): 59-64.
19. Van Walraven C, Mamdani MM, Williams JI. Inhibition of serotonin reuptake by

antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort
study. BMJ 2001;323: 655-658.
20. Electronic Medicines Compendium. Summary of product characteristics:Valdoxan.
www.medicines.org.uk
21. Drug and Therapeutics Bulletin. Withdrawing patients from antidepressants. Drug and
Therapeutics Bulletin 1999;37: 49-52.
22. Taylor LH and Kobak KA. An open-label trial of St Johns wort (Hypericum perforatum) in
obsessive compulsive disorder. Journal of Clinical Psychiatry 2000;61: 575-578.
23. Committee on Safety of Medicines and Medicines Control Agency. Reminder: St Johns
wort (Hypericum perforatum) interactions. Current problems in Pharmacovigilance
2000;26: 6.
24. National Institute for Health and Clinical Excellence. Quality standard 8: Depression in
adults. 2011. www.nice.org.uk
25. HM Government and Department of Health. Preventing suicide in England: a crossgovernment outcomes strategy to save lives. Crown Copyright 2011. www.gov.uk/
government/uploads/system/uploads/attachment_data/file/156153/PreventingSuicide-in- -A-cross-government-outcomes-strategy-to-save-lives.pdf.pdf
26. Simon GE, Savarino J, Operskalski B and Wang PS. Suicide risk during antidepressant
treatment. American Journal of Psychiatry 2006;163: 41-47.
27. Mulder RT, Joyce PR, Frampton CMA and Luty SE. Antidepressant treatment is
associated with a reduction in suicidal ideation and suicide attempts. Acta Psychiatrica
Scandinavica 2008;118(2): 116-122.
28. Medicines and Healthcare products Regulatory Agency. Antidepressants: suicidal
behaviour. Drug Safety Update 2007;1(1). www.mhra.gov.uk/Safetyinformation/
DrugSafetyUpdate/CON079102
29. Isacsson G and Ahlner J. Antidepressants and the risk of suicide in young persons
prescription trends and toxicological analyses. Acta Psychiatrica Scandinavica
2014;129(4): 296-302.
30. Depression Alliance website. www.depressionalliance.org
45
09/04/2015 14:54
Depression Book 1
Notes
46
09/04/2015 14:54
Depression Book 1
Notes
47
09/04/2015 14:54
Contacting CPPE
For information on your orders or bookings, or

any general enquiries, please contact us by email,
telephone or post. A member of our customer services
team will be happy to help you with your enquiry.
Email
info@cppe.ac.uk
Telephone
0161 778 4000
By post
Centre for Pharmacy Postgraduate Education (CPPE)
Manchester Pharmacy School
1st Floor, Stopford Building
The University of Manchester
Oxford Road
Manchester M13 9PT
Share your learning

experience with us:
email us at feedback@cppe.ac.uk
For information on all our

programmes and events:
visit our website www.cppe.ac.uk
Supported by:
Funded by:
Developed by:
CENTRE FOR PHARMACY

Depression

Book
UG500124/2
March 2015
09/04/2015 16:30
Depression Book 2
Reviewers
Foundation Trust
CPPE reviewers
Piloted by
Disclaimer
External websites
www.cppe.ac.uk
Production
09/04/2015 16:30
Learning with CPPE
Using Book 2 of focal point for pharmacy students
Case study
Clinical vignettes
11
Directing change
13
Putting your learning into practice
14
Depression Book 2
Contents
Welcome to the pharmacy student edition of CPPE focal point

The Centre for Pharmacy Postgraduate Education (CPPE) has revised this
learning programme for pharmacy students.
You can use it in three ways:
nS
elf-study: You can work through the reading, activities and cases alone.
nU
niversity-led event: Your university may have asked you to complete this
programme and could have organised seminars or workshops.
nS
tudent-led event: You may have arranged with your student colleagues to get
together to work through the cases.
We realise you may have difficulty doing some of the activities, especially those
related to practice. Think about working through these activities if you undertake
part-time or experiential work in a community pharmacy.
Please note: You are unable to attend CPPE-led events so, when the book refers to
these, please bear this in mind.
09/04/2015 16:30
Depression Book 2
Learning with CPPE

The Centre for Pharmacy Postgraduate Education (CPPE) offers a wide
range of learning opportunities in a variety of formats for pharmacy
professionals from all sectors of practice. We are funded by Health Education
England to offer continuing professional development for all pharmacists
and pharmacy technicians providing NHS services in England. For further
information about our learning portfolio, visit: www.cppe.ac.uk
1
We recognise that people have different levels of knowledge and not every
CPPE programme is suitable for every pharmacist or pharmacy technician.
We have created three categories of learning to cater for these differing
needs:

Core learning (limited expectation of prior knowledge)
Application of knowledge (assumes prior learning)

Supporting specialties (CPPE may not be the provider and will
3
direct you to other appropriate learning providers).
2
This is a
learning programme and assumes that you already have
some knowledge of the topic area.
Continuing professional development (CPD) You can use this

focal point programme to support your CPD. Consider what your
learning needs are in this area. You can record your CPD online by visiting:
www.collegeofpharmacy.com if you are a member of the BPSA or if
your school has subscribed to the CPD Online for Students service on
this website.
Programme guardians A programme guardian is a recognised expert in
an area relevant to the content of a learning programme. They will review the
programme every six months to ensure quality is maintained. We will post
any alterations or further supporting materials that are needed as an update
on our website. We recommend that you check for these updates if you are
using a programme more than six months after its initial publication date.
09/04/2015 16:30
You will have already completed Book 1 to help you identify your own
learning needs, and read the key information and related it to your own area
of practice and professional development.
Depression Book 2
Using Book 2 of focal point for

pharmacy students
This book uses a case study and clinical vignettes to help you apply what
you have learnt so far and encourages you to measure the changes in your
practice. Some suggested answers to the learning activities can be found in
Book 3.
If you are attending a university or a student-led event, you will work
through a more detailed case study and some brief clinical vignettes with
your colleagues. You will also discuss your approach to the Directing change
exercise from Book 1. If you are using this focal point for self-study, you may
wish to work through the activities by yourself or discuss your responses with
a colleague.
Just to remind you, in this programme we consider:
n the symptoms, diagnosis and classification of depression
n potential causes and risk factors
n evidence-based recommendations for the management of depression
n problems associated with the use of selective serotonin reuptake inhibitors
(SSRIs) and other antidepressants
n the burden of illness of depression.
09/04/2015 16:30
Depression Book 2
Case study Barbara

Time to prepare: 15 minutes to review and answer the questions
individually or in small groups.
Time to discuss: 15 minutes to discuss the answers with your colleagues.
Barbara is 68 years old and is a regular visitor to your pharmacy. One day,
as she collects her usual prescription, she asks your advice on which herbal
remedy to take to help her sleep.
The prescription she has just collected is for:
Drug
Dose
Bisoprolol
2.5 mg in the morning
Simvastatin
40 mg at night
Lisinopril
5 mg in the morning
Aspirin
75 mg in the morning
Paracetamol
1 g four times a day for arthritis
Barbara tells you that since her husband died about a year ago she has
not slept very well. Lately it has been worse than usual and now, as well as
having problems dropping off, she wakes in the early hours of the morning
and cannot get back to sleep. This has left her feeling weary during the day
and lacking energy.
As you look at Barbara you notice that she appears to have lost some weight
and her clothes look a little too large for her. She confirms that she has lost
weight over the past couple of months and comments that her appetite has
diminished. Barbara also says that she does not get as much exercise as she
used to. She is not attending her usual rambling group or yoga class, as she
is too tired and cant be bothered to attend. She feels guilty about letting her
friends down and that she does not feel able to get back on track.
You recall the counter assistant commenting the other day that Barbara has
not bought her usual hair colour or her favourite lipstick for a while. She
doesnt look as well groomed as normal.
09/04/2015 16:30
Focus on clinical knowledge
Depression Book 2
1. According to ICD-10, what key and ancillary

symptoms of depression does Barbara show?
Focus on patient advice
2. How would you encourage Barbara to consult her GP?
Following your conversation, Barbara makes an appointment to see her GP.
3. What other conditions would the GP rule out before

diagnosing depression?
Continued on next page
09/04/2015 16:30
Depression Book 2
Barbara returns three weeks later with a prescription for sertraline 50 mg

daily. She explains that the GP has diagnosed her with moderate depression
and mentions that she has been advised to make an appointment to see the
practice counsellor. She says she does not think this will be helpful so she
probably wont bother to make the appointment. When you ask why she feels
it will not be helpful Barbara says that she has never been one to talk much
about feelings and right now it would be too exhausting.
What factors would have influenced the prescriber to
choose sertraline for Barbara?
Focus on evidence-based medicine
4.

5. What might Barbara need to know about her

medication at this time?
09/04/2015 16:30
Depression Book 2
6. What other pharmacological and non-pharmacological

advice would you offer Barbara?
Barbara next visits your pharmacy a couple of weeks later and tells you that
she went to see her GP as her paracetamol wasnt controlling her pain. The
GP prescribed tramadol, which she started taking three days ago. Since then
she has been feeling worse more agitated and restless. She wonders if her
antidepressant isnt working any more. She also mentions that she may have
caught a bug, as she has nausea and vomiting, and is sweating, shivering and
feverish.
7. What could cause Barbara to feel like this? What advice

should you offer her?
A couple of months later Barbara comes in to the pharmacy. She tells you
that the tramadol was stopped as she had developed serotonin syndrome.
She went back to taking paracetamol. Barbara continues to take sertraline
and the dose has been increased to 100 mg daily.
09/04/2015 16:30
Depression Book 2
Barbara presents her sertraline prescription for dispensing and says that this
will probably be the last prescription she needs as she feels much better. She
tells you her sleep is much better, she now enjoys her food and has gained
the weight she lost. She has also resumed her yoga and walking activities,
and is planning to attend salsa lessons with a friend. She has read about
medicines being addictive, and when she forgot to take her tablets with
her when she stayed with friends, she experienced restlessness, sweating
and a tremor. This triggered her thinking that she may be addicted to her
medication.
8. Patients are often concerned that they may get

addicted to antidepressants. What information and
evidence could you provide to reassure Barbara?
10
09/04/2015 16:30
Time to prepare: 15 minutes to review and answer the questions

individually or in small groups.
Depression Book 2
Clinical vignettes
In this section of focal point, we look at brief clinical scenarios and

particularly focus on decision-making and communication. Review each
of the clinical vignettes and come up with a suitable response to manage the
situation. You may wish to practise these responses using role play and use
the words that you would use in the conversation.
Clinical vignette 1
Isobel visits your pharmacy and shows you an article on St Johns wort. She
asks if it would be better to use than the venlafaxine she currently takes, as
it is a natural product. You are aware that Isobel also takes a combined oral
contraceptive preparation.
Construct a response to Isobel using the words you would use in the
consultation.
Clinical vignette 2
Jamal is 27 years old and has been taking citalopram for five months. He has
been online and he is now worried because he has read about increased risk
of suicide from antidepressants. He would like some advice on the risks.
Construct a response to Jamal using the words you would use in the
consultation.
11
09/04/2015 16:30
Depression Book 2
Clinical vignette 3
Michael has been taking citalopram for the past four months and feels that
this has helped to lift his depression. However, when it comes to sexual
relations with his wife he is still having problems. Although he now feels
interested in sex, physically he is having difficulties achieving an erection. He
wonders if this is a residual symptom of his depression and if it will get better
with time.
Construct a response to Michael using the words you would use in the
consultation.
Clinical vignette 4
Sophie has previously presented with a prescription for fluoxetine, and more
recently sertraline. Today she presents a prescription for dosulepin 75 mg at
night and tells you she is no longer taking sertraline. You decide to contact
the GP.
Construct a response to Sophie, thinking about what questions you would
ask her to elicit more information. Construct a plan of what you would say
to the GP.
12
09/04/2015 16:30
Time to prepare: none you should have done this before the event.
Revisit the notes you made in Book 1 in the Directing change exercise. Discuss with your colleagues the ideas you came up with during this exercise.
What would you do differently now as a result of your learning?
Depression Book 2
Directing change
You have reached the end of the activities for this focal point event; the
remainder of this book contains follow-up activities. Suggested answers are
given in Book 3. You may wish to spend some time after the event looking
through these with colleagues.
13
09/04/2015 16:30
Depression Book 2
After your focal point event: putting

your learning into practice
Now it is time to assess your learning, determine your readiness
to change and put your new knowledge into practice.
14
09/04/2015 16:30
There are three actions you should undertake to ensure that what you have
learnt in this focal point programme influences your future practice.
1. Work through the practice activities listed below
Depression Book 2
Putting your learning into practice
2. Evaluate your learning by revisiting the Moving into focus

questions
3. Reflect on the steps for change outlined on page 17
1. Practice activities (45 minutes)
You might wish to start to put some of your learning into practice by
undertaking the following activities.
n Find out what local counselling services are available for patients and
communicate this information to your colleagues to enable them to inform
patients.
n Review the antidepressant prescribing in your area of clinical practice and
compare against national guidelines.
n Have a look at the information for patients and carers on the Depression
Alliance website: www.depressionalliance.org
n As a pharmacy team, find out about local assessment and referral criteria,
home treatment, and access and advice teams in your area.
n Work with your pharmacy team to identify and decide which resources
will be helpful for your patients and their families. Obtain these resources
and display them in your pharmacy or practice.
When will you complete these activities?
15
09/04/2015 16:30
Depression Book 2
2. Evaluate your learning (15 minutes)

The second step is to revisit the Moving into focus questions.
2. What are the differences between the presentation and treatment of mild,
moderate and severe depression?
4. What are the most clinically significant drug interactions that involve
SSRIs?
5. How long do patients have to take antidepressants for before they start
working? What are the implications of this?
6. How can you differentiate antidepressant discontinuation symptoms
from signs of addiction?
Can you answer these now?
16
09/04/2015 16:30
Depression Book 2
3. Reflection steps for change (15 minutes)

The final step is to think about the following statements and note
down how you feel about them. This should help you determine any
requirements for your further development.
I have achieved my personal learning objectives that I set myself on page 11 in
Book 1.
Strongly disagree
Disagree
Agree
Strongly agree
I have identified additional learning I need to undertake to improve my knowledge

of the therapeutic management of depression.
Strongly disagree
Disagree
Agree
Strongly agree
I would like to follow up a best practice idea expressed by a colleague at the

university or student-led event.
Strongly disagree
Disagree
Agree
Strongly agree
I would like to find out what resources and support networks are available in my
locality to support patients with depression.
Strongly disagree
Disagree
Agree
Strongly agree
After reflecting on these statements, what steps will you take now to make
them reality?
17
09/04/2015 16:30
Depression Book 2
Notes
18
09/04/2015 16:30
Depression Book 2
Notes
19
09/04/2015 16:30
Contacting CPPE

Email
info@cppe.ac.uk
Telephone
0161 778 4000
By post
Oxford Road
Manchester M13 9PT
Share your learning

experience with us:

Supported by:
Funded by:
Developed by:
09/04/2015 16:30
CENTRE FOR PHARMACY

Depression

Book
UG500124/3
March 2015
10/04/2015 08:55
Depression Book 3
Reviewers
Foundation Trust
CPPE reviewers
Piloted by
Disclaimer
External websites
www.cppe.ac.uk
Production
10/04/2015 08:55
Suggested answers
References
4
33
Depression Book 3
Contents
10/04/2015 08:55
Depression Book 3
Suggested answers
n Moving into focus questions
n Practice points
n Talking points
n Case study
nC
linical vignettes
Please remember that these
answers are suggestions only.
You should refer to local guidelines
when managing a patients
treatment for depression.
10/04/2015 08:55
Depression Book 3
These are the authors suggested responses to the learning activities and they
should be used as a guide during your focal point event. Where possible, use
your own local guidelines and policies to inform the discussion and answers.
We have provided short answers to the questions, case study and clinical
vignettes and, where appropriate, these are followed by discussion points that
provide a little more detail.
Moving into focus

The Whooley questions are two case-finding questions. They
are recommended in guidelines from the British Association for
Psychopharmacology1 and NICE clinical guidelines 90 and 912, 3 in order
to detect depression. A GP should ask these questions to a person with
depressive symptoms:
n During the past month, have you often been bothered by feeling down,
depressed or hopeless?
n During the past month, have you often been bothered by little interest or
pleasure in doing things?
I f a patient answers yes to either of these questions, they may be
depressed. If they answer no to both questions, depression is highly
unlikely.
Discussion points
Yes to both Whooley questions gives 96-97 percent sensitivity at picking
up depression, but only 57-67 percent specificity. The sensitivity (true
positive rate) is the proportion of people with the condition who have
a positive result for the condition. Specificity (true negative rate) is the
proportion of people without the condition who have a negative result.
An additional question GPs often ask when the response to either of the
above questions is yes is: do you want help with this?
10/04/2015 08:55
Depression Book 3
2. What are the differences between the presentation and treatment of

mild, moderate and severe depression?
NICE identifies mild depression as presenting with few, if any, symptoms
in excess of the five required to make the diagnosis and the symptoms result
in only minor functional impairment. Antidepressants are not recommended
for the routine treatment of mild depression. Instead, psychosocial
interventions are first-line treatment.
Moderate depression is the diagnosis if symptoms or functional
impairment are between mild and severe. Antidepressants are the
recommended treatment for moderate to severe depression, with a generic
SSRI being first-line treatment according to current guidelines.
Severe depression is where most symptoms are present and the symptoms
markedly interfere with functioning. It can occur with or without psychotic
symptoms. Antidepressants combined with psychological therapies are often
required to treat severe depression effectively.2, 3
Discussion points
n NICE uses the Diagnostic and statistical manual of mental disorders criteria
(DSM-IV) for the diagnosis of depression because the studies which
support the guidelines recommendations all used DSM-IV criteria for
inclusion of subjects in the clinical trials.4
n The World Health Organisations International Classification of Diseases
(ICD-10)5 defines the different severities of depression as follows:
nF
or mild depression a total of four symptoms must be present, of
which at least two must be key symptoms.
nM
oderate depression is the diagnosis if at least five symptoms are
present (of which two must be key), with at least three (and preferably
four) other symptoms.
nS
evere depression is where more than seven symptoms are
present, plus considerable distress and agitation unless psychomotor
retardation is a marked feature. Loss of self-esteem and feelings of
uselessness or guilt are common and suicide is a distinct danger.
Physical (somatic) symptoms are also likely to be present.
n Evidence suggests that the more severe depressive symptoms are, the
more likely patients are to respond to treatment with antidepressants.
n See Section 1.3 of Book 1 for more information.
10/04/2015 08:55
Depression Book 3

n Increased anxiety, especially at the start of treatment.
n Gastrointestinal effects such as nausea, vomiting and diarrhoea.
n Sexual dysfunction.
n Abnormal bleeding, especially in the elderly and in those taking
aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) or
anticoagulants.6, 7
Full side-effect profiles for each SSRI can be found in the individual
summary of product characteristics.
Discussion points
n Although it can be a consequence of a depressive illness, sexual
dysfunction is a side-effect and often a reason for poor adherence to
treatment with SSRIs, especially if it continues after the depression has
started to resolve. Pharmacists should not shy away from discussing this
issue, as alternative treatments are available and good adherence is vital
for a good outcome.
n Increased anxiety and gastrointestinal side-effects are usually transient
and can be minimised by using a low starting dose and titrating upwards
slowly.
n See Section 3.2 of Book 1 for more information.
4. What are the most clinically significant drug interactions that
involve SSRIs?
n Increased risk of bleeding with aspirin, other NSAIDs or anticoagulants.
n Increased risk of serotonin syndrome with other antidepressants that
increase serotonin transmission.
n Increased risk of serotonin syndrome with triptans and other medicines,
such as tramadol, that increase serotonin transmission.3
n Increased risk of neurotoxicity with lithium.
You can find information about other drug interactions in the British
National Formulary (BNF).8
10/04/2015 08:55
Depression Book 3
Discussion points
n SSRIs should not be prescribed for a person taking aspirin or other
NSAIDs without concomitant gastrointestinal protection with a proton
pump inhibitor.2
n SSRIs should not be prescribed with triptans.
n SSRIs are contraindicated with warfarin and other anticoagulants.
n Combined antidepressant treatment should always be used with caution.
nS
witching antidepressants should always be conducted cautiously, by
taking into account any potential risk of serotonin syndrome.
5. How long do patients have to take antidepressants for before they
start working? What are the implications of this?
n Antidepressants are now thought to start working within the first two
weeks of treatment.
n NICE recommends that antidepressant treatment should be reviewed
after two weeks. If there is no improvement within the first two to
four weeks adherence should be checked. If there is still an inadequate
response after three to four weeks despite good adherence, an increase in
dose or preferably a change in antidepressant should be considered.2
Discussion points
n In the past antidepressants were thought to take up to six weeks to work,
although some initial improvement may have be seen between two to four
weeks. This is no longer thought to be the case.
n Antidepressants may start to work within the first two weeks of treatment
but in clinical trials this is obscured by a strong response to placebos. In
clinical trials both placebos and antidepressants show an effect by week
one. This increases with time and significant separation from placebo
usually occurs at week four.9
n With the exception of sertraline, or unless the person is a fast metaboliser,
an increase in dose of the antidepressant is unlikely to increase its effect
but is likely to result in an increase in side-effects. If a person isnt
responding to an antidepressant, the next step is to switch to another
SSRI or to a better tolerated, newer generation antidepressant.2
n In the elderly, treatment should be maintained for at least eight to ten
weeks before deciding to switch, as time to respond may be longer.
10/04/2015 08:55
n Antidepressant use does not result in craving, tolerance* or primacy,**

however these are three key features of addiction to drugs of dependence.
n When a person stops an antidepressant abruptly they may suffer transient
discontinuation symptoms which may enforce the need to continue taking
the antidepressant but they do not crave it.
Depression Book 3
6. How can you differentiate antidepressant discontinuation

symptoms from signs of addiction?
*Tolerance means requiring increasing doses to achieve the same or desired

effect. This does not occur with antidepressants.
**Primacy is when a person risks all: money, employment, relationships and
health in order to obtain supplies of their drug of addiction. They may even
engage in illegal activities. This does not occur with antidepressants.
Discussion points
n There is no evidence that antidepressants are addictive in the same way as
opiates and benzodiazepines.
n Many patients confuse antidepressants with benzodiazepines and stop
their treatment prematurely because they fear addiction, dependence or
tolerance.
n Some antidepressants are associated with discontinuation symptoms. It
is important to address this when providing information and advice to
patients who are prescribed antidepressants. It is important to distinguish
such discontinuation symptoms from the withdrawal syndrome seen on
stopping a drug of dependence.
10/04/2015 08:55
Depression Book 3
Practice and talking points

Talking point A
Why are many people reluctant to seek help when they have symptoms of
depression?
People with symptoms of depression may:
n be reluctant to admit this because of the stigma associated with depression
n not believe there is an effective treatment for their condition
n have been depressed for a long time and adjusted to the symptoms and
regard them as normal
n not have enough energy
n recognise they have depression but have language difficulties which make
communication difficult
n be unable to recognise and communicate their symptoms.
Discussion points
n Pharmacy professionals have a role to play in opening discussions with
people who may appear to be depressed and encouraging them to
consult their GP or contact a patient support group.
n Pharmacy professionals can intervene with patients who frequently make
requests for over-the-counter hypnotics or herbal remedies, as this may
be a sign of depression or other condition that needs to be investigated.
10
10/04/2015 08:55
Depression Book 3
Practice point 1
What symptoms of depression do you most commonly see in your
practice? Why does depression not always get recognised?
The following are examples of common symptoms of depression that you
may see or hear described by patients:
n Low mood
n Lack of enjoyment
n Negative thoughts
n Feeling physically tired
n Sleep disturbance
n Agitation
n Weight changes
n Difficulty concentrating
Why is depression not always recognised?
n A person may present with physical symptoms which mask depression.
n A person may have depression with a co-existing physical illness which is
focused on at the expense of their depressive symptoms.
n Once depression has been missed, it often remains undiagnosed.
n Personal bias towards or against diagnosing depression, or even stigma
among professionals, may affect whether cues are recognised.
n Good consultation skills and knowledge of depression are crucial in making
a diagnosis these may be lacking.
n It may be difficult for GPs to recognise if a person is depressed in the
limited time they have for appointments.
Discussion points
n Depression may manifest itself as physical symptoms and physical
symptoms may be present in all severities of depression.
n People with a chronic physical illness are at risk of developing depression.
n Many people with a chronic physical illness do also suffer from
depression.
n Others may not believe that effective treatment is available or they may
fear addiction to antidepressants.
n A person may be afraid of admitting to depressive symptoms because of

the stigma attached to a diagnosis of depression.
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Depression Book 3
Practice point 2
Which medicines or groups of medicines are associated with
causing depressive symptoms?
A number of prescription medicines have been associated with depressive
symptoms. Here are some of the more common medicines:
n Corticosteroids
n Antihypertensives (for example, reserpine, methyldopa, propranolol,
diltiazem, nifedipine)
n Oral contraceptives
n Cimetidine
n NSAIDs
n Opiates
The BNF provides additional information on adverse effects of drugs.8
Discussion points
n Mood disturbance may also be due to the effect of a physical or organic
illness.
n Some illnesses may cause symptoms that mimic those of
depression, such as lethargy and tiredness. Such illness may include:
hypothyroidism, stroke, multiple sclerosis, occult carcinoma, metabolic
and endocrine disorders (eg, Cushings disease), viral infections,
anaemia and low blood pressure. These should be eliminated before a
firm diagnosis of depression is made.
Practice point 3
What local and national self-help groups and resources are available
for someone living with depression?
Local self-help groups will depend on local availability. Some of the national
self-help groups and resources that you could signpost patients to include:
n Mind (www.mind.org.uk)10
n Depression Alliance (www.depressionalliance.org)11
nD
epression UK (www.depressionuk.org)12
nN
HS Choices (www.nhs.uk)13
nC
hoice and Medication (www.choiceandmedication.org)14
12
n Rethink Mental Illness (www.rethink.org)15
10/04/2015 08:55
Depression Book 3
Discussion points
n Antidepressants are not recommended for mild depression. Instead,
psychosocial interventions are first-line treatment.
n People with all severities of depression may benefit from attending local
support groups.
n Some GP practices are able to prescribe exercise and regular attendance
at a local fitness centre as there is evidence that this can be helpful.
n Self-help books and online resources may also be of interest to some
patients.
n The NICE guidance specifically written for patients and carers can be
helpful in explaining the illness and its management.16
Talking point B
How can you encourage good adherence to antidepressant treatment in a
person with depression, in order to achieve the best outcome for them?
n Emphasise that antidepressants are not addictive and must be taken
regularly for at least six months after remission of symptoms. Those at risk
of recurrence may need to take them for longer.
n Warn people of the risks of discontinuation symptoms if doses are missed
or treatment stopped abruptly, but reassure them that these are usually
transient and not life-threatening.
n Differentiate between discontinuation symptoms and addiction.
n Explain that all medicines have side-effects but not everyone is troubled
by them.
n Discuss side-effects and how to manage them should they occur.
n Provide information to allow patients choice (for example:
http://whatyoushouldknow.depression-alliance.co.uk/choice/
choosing-antidepressants).11
Discussion points
n Check what the patient already understands about their illness and its
treatment.
n Any verbal information provided should be backed up and supplemented

with written information. The Choice and Medication website provides
some useful written information.14 You can normally access the
website through a local NHS trust if it has a subscription. Community
pharmacists and independent healthcare providers are also able to
subscribe.
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Depression Book 3
n Current evidence suggests that in order to maintain a long-term

improvement in adherence, information about the condition and its
treatment must be provided on an ongoing basis and not just at first
diagnosis or with the initial prescription.17, 18
n For further learning and development access the CPPE Consultation
skills for pharmacy practice: taking a patient-centred approach distance
learning programme and the website:
www.consultationskillsforpharmacy.com
Practice point 4
The cost to the individual and to society of untreated or
inadequately treated depression is enormous. Effective treatment
not only relieves human suffering but also helps restore function,
reduce disability and lower costs. The burden imposed on family,
carers and society as a whole is reduced if depression is recognised
early and treated promptly and effectively.
How can a member of the pharmacy team assist with this?
n Recognise that a person with depression has an illness.
n Emphasise that their symptoms are not signs of character weakness.
n Be alert for any suicidal thoughts or intentions, especially at the start of
treatment or following a dose increase.
n Inform people that psychological therapies and medicines are effective.
n Reassure them that antidepressants are not addictive.
n Provide adherence support if they are prescribed an antidepressant.
n Signpost them to any website, group or other source of information or
support that may be helpful.
14
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Depression Book 3
Case study Barbara

Barbara is 68 years old and is a regular visitor to your pharmacy. One day,
as she collects her usual prescription, she asks your advice on which herbal
remedy to take to help her sleep.
The prescription she has just collected is for:
Drug
Dose
Bisoprolol
2.5 mg in the morning
Simvastatin
40 mg at night
Lisinopril
5 mg in the morning
Aspirin
75 mg in the morning
Paracetamol
1 g four times a day for arthritis
Barbara tells you that since her husband died about a year ago she has
not slept very well. Lately it has been worse than usual and now, as well as
having problems dropping off, she wakes in the early hours of the morning
and cannot get back to sleep. This has left her feeling weary during the day
and lacking energy.
As you look at Barbara you notice that she appears to have lost some weight
and her clothes look a little too large for her. She confirms that she has lost
weight over the past couple of months and comments that her appetite has
diminished. Barbara also says that she does not get as much exercise as she
used to. She is not attending her usual rambling group or yoga class, as she
is too tired and cant be bothered to attend. She feels guilty about letting her
friends down and that she does not feel able to get back on track.
You recall the counter assistant commenting the other day that Barbara has
not bought her usual hair colour or her favourite lipstick for a while. She
doesnt look as well groomed as normal.
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Depression Book 3
1. According to ICD-10, what key and ancillary

symptoms of depression does Barbara show?
n Disturbed sleep
n Loss of interest and enjoyment

n Reduced energy, leading to increased fatigability and

diminished activity
n Ideas of guilt and worthlessness

n Diminished appetite and weight loss
Discussion points
n Barbara initially asks about something to help her sleep. She has
the classic combination of difficulty in getting off to sleep and early
morning wakening that are common in depression. Chronic insomnia is
not only a symptom but is also a cause of depression.
n She has lost weight and recognises her appetite has diminished. She
says that she is lacking energy and she appears to be attributing this to
not sleeping, however this is a common symptom of depression.5
nS
he no longer attends her usual activities because she is tired and cant
be bothered. In the ICD-10 classification system this is noted as loss of
interest and enjoyment.5
n Barbara is also expressing feelings of guilt, which is an ancillary
symptom in the ICD-10 classification system.5
nS
he has two key symptoms (reduced energy and motivation, and
loss of interest and enjoyment) and at least three ancillary symptoms
(disturbed sleep, diminished appetite and weight loss, along with ideas
of guilt and worthlessness) within this classification.5
n Barbara is not paying as much attention to her appearance as she used
to, which is common in depression. This could be due to reduced selfesteem and self-confidence, which is another ancillary symptom in the
ICD-10 classification system.5
n According to DSM criteria, Barbara has five symptoms, of which one
is key.
16
10/04/2015 08:55
n Build rapport and demonstrate empathy. Establish common

ground and ideas.
n Use open questions to explore Barbaras own ideas of why
she is unable to sleep.
Depression Book 3
2. How would you encourage Barbara to consult her GP?
n Help her voice her concerns and what the underlying

causes could mean for her.
n Encourage her to communicate her expectations and
empower her to plan how she can move forward with her
decisions and conclusions.
n Use the ICE mnemonic (Ideas, Concerns, Expectations)
to establish Barbaras perspective. You can find further
details of this in the CPPE Consultation skills for pharmacy
practice: taking a patient-centred approach distance learning
programme.
n Summarise key messages from the consultation to check
understanding on both sides.
Discussion points
n Think about the words you use when talking to people about
depression? How many different ways can you think of to talk about
depression? Some suggestions: feeling low, low mood, feeling down,
feeling blue/grey, sad, dejected, despondent, downhearted, flat, heavy,
hopeless, helpless, joyless, pessimistic, sombre, unhappy, wretched, dull,
gloomy.
n Ask Barbara when she first noticed her symptoms and identify any links
with other factors, such as change in medication.
n Sleeplessness may be related to several conditions and Barbara needs to
let her GP know about it. There are various courses of action that the
GP may suggest.
Following your conversation, Barbara makes an appointment to see her
GP.
17
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n Chronic fatigue syndrome

n Infection
Depression Book 3
3. What other conditions would the GP rule out before

diagnosing depression?
n Hypothyroidism
n Anaemia low vitamin B12/folate/iron levels
n Exacerbation of cardiovascular factors
n Side-effects from medicines (lisinopril, bisoprolol,
simvastatin)
n Anxiety
n Cancer
n Organic causes, such as dementia, multiple sclerosis, stroke
n Metabolic and endocrine disorders, such as Cushings
disease
Discussion points
n Chronic fatigue syndrome would lead to feeling tired and lethargic.
n Infection can leave people feeling tired and low on energy.
n Hypothyroidism could lead to feelings of tiredness, although people
may gain weight with this.
n Low vitamin B12/folate/iron levels can leave people feeling tired and
may lead to slowing of thoughts or difficulty concentrating.
n Exacerbation of cardiovascular factors can affect sleep and leave people
feeling lethargic and tired.
n Depression can be a side-effect of some medications. See the BNF 8 for
information on side-effects of lisinopril, bisoprolol and simvastatin.
nA
nxiety can lead to lack of sleep, tiredness, diminished appetite.3
nS
ymptoms of cancer include weight loss and feeling tired.
nA
person with dementia, multiple sclerosis or stroke may present
with lack of confidence, poor concentration and slowing of thought
processes.3
nT
here are links between depression and the endocrine system, notably
cortisol release.3
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Depression Book 3
Barbara returns three weeks later with a prescription for sertraline 50

mg daily. She explains that the GP has diagnosed her with moderate
depression and mentions that she has been advised to make an
appointment to see the practice counsellor. She says she does not think
this will be helpful so she probably wont bother to make the appointment.
When you ask why she feels it will not be helpful Barbara says that she has
never been one to talk much about feelings and right now it would be too
exhausting.
4. What factors would have influenced the prescriber to
choose sertraline for Barbara?
Focus on evidence-based medicine
n SSRIs are usually prescribed first-line for moderate

depression.2
n SSRIs are generally safe for people with cardiovascular
disease.3
n Sertraline has no significant interactions with Barbaras
other medicines.8, 19
n Sertraline can be combined with psychological therapy, as
suggested by NICE guidelines.2
n GPs usually prescribe SSRIs, so the GP will have more
knowledge of this than some other antidepressants and may
feel more competent to prescribe it.
n There may be a local formulary or care pathway that may
also guide the choice of treatment.
Discussion points
n Sertraline is an SSRI antidepressant and SSRIs are usually first choice
for depression.2
n Sertraline will increase the risk of gastrointestinal bleeding if taken with
aspirin so you should suggest to the prescriber that Barbara is also
prescribed a proton pump inhibitor.2
n With SSRIs there is lower risk of toxicity, especially in overdose, than
older antidepressants.20
n Sertraline has less side-effects than older drugs, such as the tricyclic
antidepressants, and these side-effects are often milder.8
19
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Depression Book 3
5. What might Barbara need to know about her

medication at this time?
n Take one tablet a day, usually in the morning to avoid
further sleep disturbances.
n It is best taken with or after food to minimise nausea
and other gastric side-effects. Nausea and diarrhoea are
common at the beginning of treatment but they usually
resolve with continued use.
n A
ntidepressants need time to work, they are not instant
pick-me-ups. Friends and family may notice small changes
within a week and more changes as time progresses. However,
Barbara may not notice improvements for several weeks. One
of the first improvements may be an increase in energy.
n Often people may feel worse for the first few weeks and
then start to feel better.
n Sleep may actually be worse for the first few weeks but this
will improve.
n Suggest she makes an appointment to see the GP about two
weeks after starting the antidepressant.2
n Encourage Barbara to make the appointment with the
practice counsellor.
n Barbara should continue taking her antidepressant for at least
six months after her symptoms have completely resolved to
reduce the risk of relapse and her symptoms recurring.
Discussion points
n Sertraline is usually given once a day because it has a half-life of about
24 hours. It is unusual for sertraline to cause drowsiness so it is often
taken in the morning. If people do experience drowsiness as a sideeffect it is safe to take it at night.
n Nausea is the most common undesirable effect. Most undesirable
effects are dose-dependent and often transient in nature and will
resolve with continued treatment.
n Insomnia occurs in 19 percent of patients. Again this is usually selflimiting, and as sleep disturbance is a symptom of depression this
side-effect often resolves.21 A benzodiazepine or other hypnotic can be
added in for a limited time if insomnia is a major issue.
20
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Depression Book 3
nN
ICE clinical guidelines 90 and 91 say that a practitioner should
support and encourage a person who has benefited from taking an
antidepressant to continue medication for at least six months after remission
of an episode of depression. Discuss with the person that:
n this greatly reduces the risk of relapse
n antidepressants are not associated with addiction.2, 3
n I f this was not Barbaras first episode of depression, it would be
appropriate for her to continue taking the antidepressant for two years
after remission.2
n Barbara is aged over 30 so according to NICE guidelines she should be
followed up by the GP after two weeks to check for thoughts of suicide.2
6. What other pharmacological and non-pharmacological
advice would you offer Barbara?
n She should see the GP and ask for a proton pump inhibitor
to protect her stomach, as she is at risk of a gastric bleed
with the combination of an SSRI antidepressant and
aspirin.
n Encourage Barbara to attend the counselling.
n Advise her to eat healthily.
n Encourage her to get out of the house, and take regular
exercise.
n Signpost her to local support groups, such as Mind,10
Depression Alliance11 and Rethink Mental Illness.15 Offer
information on useful websites or books and leaflets.
Discussion points
n The risk of bleeding with an SSRI antidepressant is increased if it is

taken with aspirin. Platelets release serotonin in response to injury.
This promotes vasoconstriction and produces morphological changes
in the platelets that aid aggregation. Platelets also have a serotonin
transporter to allow reuptake of serotonin and this is blocked by SSRI
antidepressants, so SSRIs deplete platelet serotonin. SSRIs also increase
gastric acid secretion and the risk of gastric ulcers. Co-prescribing of
aspirin with an SSRI more than doubles the risk of a gastrointestinal
bleed and older people are at even greater risk. The addition of a proton
pump inhibitor, such as omeprazole or lansoprazole according to local
formulary choice, can help reduce the risk of gastrointestinal bleeds.20
21
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Depression Book 3
nN
ICE recommends psychological therapies for mild depression, and
psychological therapies together with pharmacotherapy in moderate to
severe depression.2 Primary care psychology services are available. The
services may differ slightly between areas. They are available in the GP
surgery and patients can self-refer. Other options would be computerbased cognitive behavioural therapy programmes, such as Beating the
blues,22 and these may be accessed via the GP surgery.
nT
he neurotransmitters involved in depression are manufactured from
amino acids. Some studies have shown fish oils to be of benefit,1 and
general healthy eating, with plenty of fruit and vegetables, can help
people keep healthy. Cutting back on alcohol and caffeine can help
sleep and improve mood. There is a section on healthy eating and
exercise on the Depression Alliance website.11
n The charity Mind runs ecotherapy groups in some areas. These groups
use nature activities, such as walking, cycling and pet therapy to
promote wellbeing. You can find more details on the Mind website.10
nW
hen undertaking medicines use reviews (MURs)/medication
reviews with patients with depression, make sure you offer advice
on sleep hygiene, healthy eating, exercise, self-help books, and local
mental health support groups and activities.
Barbara next visits your pharmacy a couple of weeks later and tells you that
she went to see her GP as her paracetamol wasnt controlling her pain. The
GP prescribed tramadol, which she started taking three days ago. Since
then she has been feeling worse more agitated and restless. She wonders
if her antidepressant isnt working any more. She also mentions that she
may have caught a bug, as she has nausea and vomiting, and is sweating,
shivering and feverish.
7. What could cause Barbara to feel like this? What advice

should you offer her?
Some possibilities
n Serotonin syndrome
n Flu or other infection
n Rhabdomyolysis
n Discontinuation symptoms
22
10/04/2015 08:55
n Barbara shows several symptoms of serotonin syndrome

and it is difficult to assess the degree and severity of these.
She needs to be assessed and triaged within a few hours.
She should go to a GP surgery, local walk-in centre,
or accident and emergency. She will need to maintain
hydration so she could take water with her to drink.
Also, she should try and keep her temperature down by
mechanical rather than pharmacological means. She can
remove excess layers of clothing and use a tepid damp cloth
to cool her skin.
Depression Book 3
Advice
n Advise Barbara not to take any more tramadol or sertraline

until she has seen a doctor and her symptoms have resolved.
Discussion points
n The most likely diagnosis is serotonin syndrome as Barbara is on an
SSRI antidepressant and tramadol, which both increase free serotonin
levels.
n She will need blood tests to check for kidney injury, muscle damage (a
symptom of rhabdomyolysis), liver problems and infection.
n She may need scans, depending on her symptoms. These may include
a chest X-ray if respiration is affected or a CT scan if she displays
confusion or other neurological signs. An ECG can detect changes in
heart rhythm.
n Benzodiazepines are often used as standard treatment for serotonin
syndrome and may be prescribed to help Barbara, especially as she is
restless and agitated.
n Serious cases of serotonin syndrome are treated with 5-HT2A
antagonists. Cyproheptadine can be used at a dose of 12 mg to start
and then 4-8 mg every six hours. Chlorpromazine can be given in
severe cases (12.5-25 mg intravenously to start and then 25 mg orally
every six hours until symptoms subside).
A couple of months later Barbara comes in to the pharmacy. She tells you
that the tramadol was stopped as she had developed serotonin syndrome.
She went back to taking paracetamol. Barbara continues to take sertraline
and the dose has been increased to 100 mg daily.
2
Barbara presents her sertraline prescription for dispensing and says that
this will probably be the last prescription she needs as she feels much
23
10/04/2015 08:55
Depression Book 3
better. She tells you her sleep is much better, she now enjoys her food and
has gained the weight she lost. She has also resumed her yoga and walking
activities, and is planning to attend salsa lessons with a friend. She has
read about medicines being addictive, and when she forgot to take her
tablets with her when she stayed with friends, she experienced restlessness,
sweating and a tremor. This triggered her thinking that she may be addicted
to her medication.
24
10/04/2015 08:55
n T
here is a difference between addiction and discontinuation
symptoms.
Depression Book 3
8. Patients are often concerned that they may get

addicted to antidepressants. What information and
evidence could you provide to reassure Barbara?
n I f a person is addicted to a drug/medicine they need to keep

increasing the dose to have the same effect as they build up
tolerance.
n W
hen taking an antidepressant, the dose has a consistent
effect and discontinuation symptoms only occur if the
medicine is stopped or reduced suddenly.
n A
patient on an antidepressant does not crave it once it has
been stopped, nor would they risk all in order to obtain
further supplies, as can be seen with addiction (see Moving
into focus question 6 for further information).
n A
dvise Barbara that if she gradually tapers off the sertraline
under her GPs supervision, she shouldnt experience these
unpleasant effects.
Discussion points
nY
ou could advise Barbara that it takes the body time to adapt to change.
It took a while for her body to get used to the sertraline and the same
is true when you take the sertraline away. It takes around three weeks
for the brain to adjust to changes (the brain will have replaced most
receptors within three weeks and will have up-regulated or downregulated as needed to compensate). It is best to reduce the sertraline
gradually to allow this regulation to happen. For a first episode of
depression, medication should be continued for at least six months after
remission. It would be a good idea for Barbara to continue treatment
for at least six to nine months after her symptoms have completely
resolved in order to remain well.
nS
ertraline should be discontinued over about a month. If Barbara
experiences discontinuation symptoms on a gentle reduction and
stopping of the sertraline, it can be switched to fluoxetine which has
a much longer half-life. This can gradually be withdrawn over time.
Encourage Barbara to engage with her GP to reduce and stop sertraline
gradually when she is ready to come off it.
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Depression Book 3
Clinical vignettes
Clinical vignette 1
Isobel visits your pharmacy and shows you an article on St Johns wort. She
asks if it would be better to use than the venlafaxine she currently takes, as
it is a natural product. You are aware that Isobel also takes a combined oral
contraceptive preparation.
Construct a response to Isobel using the words you would use in the
consultation.
The bottom line
She should continue with the venlafaxine she already takes. St Johns wort
would reduce the effectiveness of her oral contraceptive medicine and
would not be a recommended treatment choice for her. Isobel should not
take St Johns wort with venlafaxine due to the risk of serotonin syndrome.
If after your discussion she would like to take St Johns wort, then she
would need to discuss this with her prescriber.
Why?
If she stops venlafaxine suddenly she could experience discontinuation
symptoms, such as:
n dizziness, light headedness, vertigo, ataxia
n nausea, vomiting, diarrhoea
n lethargy, headache, tremor, sweating, anorexia
n paraesthesia, numbness, electric shock like sensations
n irritability, anxiety, agitation, low mood.
There are many preparations of St Johns wort that vary in the amount
of hypericum they contain. As it is classed as a herbal remedy it is not
regulated in the same way as the venlafaxine she already takes.
Supporting the statements
St Johns wort interacts with progesterone, and may slightly reduce the
levels of desogestrel and ethinylestradiol via enzyme induction, speeding
up the metabolism of the hormones. This leads to reduced efficacy and
increased risk of pregnancy.19 Any change in treatment from venlafaxine to
St Johns wort may need a change in contraception as well, especially if a
low dose hormonal preparation is used.
26
10/04/2015 08:55
NICE clinical guideline 90 states that although there is evidence that St Johns
wort may be of benefit in mild or moderate depression, practitioners should:
Depression Book 3
There is variation in St Johns wort preparations. Some are measured by the

weight of the herb before processing, some use the dried herb weight and others
state the dose of hypericum. If therapy is started, it is best to stick to one brand.
n not prescribe or advise its use by people with depression because of uncertainty
about appropriate doses, persistence of effect, variation in the nature of
preparations and potential serious interactions with other drugs (including oral
contraceptives, anticoagulants and anticonvulsants)
n advise people with depression of the different potencies of the preparations available
and of the potential serious interactions of St Johns wort with other drugs.2
A Cochrane review in 2009 reviewed 29 studies comparing St Johns wort
to placebo or standard antidepressants on over 5000 people. They found
St Johns wort to be better than placebo and as effective as antidepressants.
Interestingly, they found that St Johns wort did better in countries where
German was spoken and traditionally in these cultures physicians have
prescribed this treatment. The results of this review apply only to the
preparations tested in the studies included, and possibly to extracts with
similar characteristics.23 It is important to note that this review looked at
short-term studies up to 12 weeks, which is much shorter than the time an
antidepressant should be taken for to reduce the chance of relapse.
The British Association for Psychopharmacology evidence-based guidelines
state similar findings that St Johns wort is more effective than placebo and
is as effective as antidepressants (in doses between 600 mg and 1800 mg).1
Patients suffering from depressive symptoms who wish to use St Johns wort
should consult a health professional. Using a St Johns wort extract might
be justified but important issues should be taken into account, for example,
St Johns wort products available on the market vary to a great extent.
Side-effects of St Johns wort extracts are usually minor and uncommon.
However, the effects of other drugs might be significantly compromised.
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Depression Book 3
Clinical vignette 2
Jamal is 27 years old and has been taking citalopram for five months. He
has been online and he is now worried because he has read about increased
risk of suicide from antidepressants. He would like some advice on the risks.
Construct a response to Jamal using the words you would use in the consultation.
The bottom line
Jamal is past the period of highest risk of his treatment (the first few
weeks). The risk of suicide while taking the medicines must be weighed
up against the risk of suicide without treatment. If his antidepressant is
working for him, he should continue until he and his prescriber decide he
should stop. He should take it for at least six months after remission if this
is his first episode. If it is not working, he should visit his prescriber for a
review of treatment.
Why?
Suicide risk is greater in the month before treatment, so treatment helps
reduce the risk for most people.2
Risk of suicide while on treatment is greatest in the first few weeks of
therapy. It reduces as treatment continues, so Jamal would be at less risk
now with the antidepressant than he was when he started, if it is working
for him.
NICE clinical guideline 90 states that people started on antidepressants
who are not considered to be at increased risk of suicide should be reviewed
after two weeks. They should then be reviewed at regular intervals (every
two to four weeks) in the first three months, and then at longer intervals if
response is good.2
A patient with depression who is started on antidepressants, and who is
thought to be at an increased suicide risk, or is younger than 30 years old,
should normally be seen after one week. They should be reviewed frequently
after that until they are no longer considered to be at increased risk.2
28
You could ask Jamal if he currently has any thoughts of harming himself.
People are often remarkably honest and asking the question does not
increase the risks of self-harm. If he says he does have thoughts of harming
himself, the next step would be to explore if he has a plan and if so what his
plan is.
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Depression Book 3
The World Health Organisations guide for the Mental Health Gap
Action Programme advises that anyone over 10 years of age experiencing
depression, psychosis, dementia, behavioural or learning difficulties, alcohol
or drug use or epilepsy should be asked about thoughts of self-harm in
the last month and acts of self-harm in the last year. It states that asking
about self-harm does not promote acts of self-harm. It often reduces the anxiety
associated with thoughts or acts of self-harm and helps the person feel understood.
However, try and establish a relationship with the person before asking questions
about self-harm. Ask the person to explain the reasons for harming themselves.24
Clinical vignette 3
Michael has been taking citalopram for the past four months and feels that
this has helped to lift his depression. However, when it comes to sexual
relations with his wife he is still having problems. Although he now feels
interested in sex, physically he is having difficulties achieving an erection.
He wonders if this is a residual symptom of his depression and if it will get
better with time.
Construct a response to Michael using the words you would use in the
consultation.
The bottom line
This could be due to his treatment, as sexual dysfunction is a common
side-effect of antidepressants that inhibit serotonin reuptake.
You should encourage Michael to explain the problem to his GP. A
different antidepressant that is less likely to cause this side-effect, such as
mirtazapine, or additional medication to manage this side-effect could be
prescribed.
He should continue his current treatment until his GP implements any
changes, and work with his GP during any change to his prescription.
Why?
Impotence, ejaculation disorder and ejaculation failure are listed as
common side-effects of citalopram. Serotonin neurones descend from
the brain down the spinal cord and have a role to play in ejaculation and
orgasm. As this medicine affects serotonin reuptake on these neurones, it
affects sexual function.
2
29
10/04/2015 08:55
Depression Book 3

The British Association for Psychopharmacology guideline for treating
depressive disorders with antidepressants includes a useful table comparing
side-effects of different antidepressants. It also provides advice on strategies
in the management of this side-effect, such as switching treatment or adding
sildenafil.1
There are some useful graphs on the Depression Alliance website
that show the incidence of certain side-effects in clinical trials: http://
whatyoushouldknow.depression-alliance.co.uk/choice/choosingantidepressants/#impotence
You should reassure Michael that it is likely to be a side-effect of the
medication rather than part of the depression, and can be resolved.
Emphasise that this is common and is a reason why many people stop
treatment.25
30
10/04/2015 08:55
Sophie has previously presented with a prescription for fluoxetine, and

more recently sertraline. Today she presents a prescription for dosulepin
75 mg at night and tells you she is no longer taking sertraline. You decide to
contact the GP.
Depression Book 3
Clinical vignette 4
Construct a response to Sophie, thinking about what questions you would

ask her to elicit more information. Construct a plan of what you would say
to the GP.
The bottom line
Explore Sophies expectations and understanding of her treatment.
You need to find out why her treatment has been changed twice. Is it
inadequate efficacy, side-effects or has Sophie not taken her medication in
a therapeutic dose for long enough?
Dosulepin is not appropriate. NICE clinical guidelines 90 and 91 suggest
dosulepin should not be initiated.2, 3 Other antidepressants are less toxic
in overdose, have a different, milder side-effect profile and pose less risk.
Suggestions would include mirtazapine or a serotonin-noradrenaline
reuptake inhibitor (SNRI), such as venlafaxine.
Why?
NICE guidelines suggest dosulepin should not be used.2, 3
It is the most toxic tricyclic antidepressant (TCA) in overdose and TCAs
are more toxic in overdose than SNRIs or SSRIs.26
Dosulepin is generally less well tolerated than SSRIs, SNRIs or
mirtazapine.1
You need to be certain that the change in treatment is due to lack of
efficacy rather than poor adherence (non-intentional or intentional) or
intolerance. The root cause of the problem should be determined in order
to discuss the next logical step in Sophies treatment.
31
10/04/2015 08:55
Depression Book 3

NICE clinical guideline 90 states that when prescribing drugs other than
SSRIs, take the following into account:
n t he increased likelihood of the person stopping treatment because of side-effects
(and the consequent need to increase the dose gradually) with venlafaxine,
duloxetine and TCAs
n t he specific cautions, contraindications and monitoring requirements for some
drugs
nd
osulepin should not be prescribed.2
There is evidence that dosulepin is toxic in overdose and presents a greater
risk than other antidepressants.26
Mirtazapine, SNRIs and other TCAs need to be tried before dosulepin. The
recommendations of the stepped approach as adopted in the UK state that
starting a person on dosulepin should only be done by specialists. There are
other treatments that the GP could initiate before dosulepin is considered.2
NICE clinical guideline 90 suggests a generic SSRI should be used for
first-line treatment of depression (Step 1). If treatment has to be changed, it
should initially be switched to a different SSRI or a better tolerated, newer
generation antidepressant (Step 2). Subsequently, an antidepressant of a
different class that may be less well tolerated (such as venlafaxine, a TCA or
a monoamine oxidase inhibitor) should be considered (Step 3).2
Sophie may not have had an adequate trial of the previous antidepressants.
Pharmacy professionals are in an ideal place to find out if this is due to
side-effects, intolerance or non-adherence. You could use the ExcEllEncE
model of Explore, Educate, Enable and Empower to find out why
Sophies medicine has been changed and to help her get the most from
her treatment.27, 28 To find out more about the ExcEllEncE model, access
the CPPE Consultation skills for pharmacy practice: taking a patient-centred
approach distance learning programme.
32
10/04/2015 08:55
1. Anderson IM et al. Evidence-based guidelines for treating depressive disorders with antidepressants:
a revision of the 2000 British Association for Psychopharmacology guidelines. British Association
for Psychopharmacology. 2008. www.bap.org.uk
Depression Book 3
References
2. National Collaborating Centre for Mental Health. Depression: The NICE guideline on the
treatment and management of depression in adults (updated edition). The British Psychological
3. National Collaborating Centre for Mental Health. Depression in adults with a chronic physical
health problem: The NICE guideline on treatment and management. The British Psychological
DSM-IV. Fourth edition. Virginia: American Psychiatric Association; 1994.
5. World Health Organisation. Classifications: International Classification of Diseases (ICD).
www.who.int/classifications/icd/en/
6. Dalton SO et al. Use of selective serotonin reuptake inhibitors and risk of upper
gastrointestinal tract bleeding a population-based cohort study. Archives of Internal Medicine
2003;163(1): 59-64.
7. Van Walraven C, Mamdani MM, Williams JI. Inhibition of serotonin reuptake by
antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort
study. BMJ 2001;323: 655-658.
8. Joint Formulary Committee. British National Formulary 67. London: Pharmaceutical Press;
2014.
9. Taylor MJ, Freemantle N, Geddes JR, Bhagwagar Z. Early onset of selective serotonin
reuptake inhibitor antidepressant action systematic review and meta-analysis. Archives of
General Psychiatry 2006;63(11): 12171223.
10. Mind website. www.mind.org.uk
11. Depression Alliance website. www.depressionalliance.org
12. Depression UK website. www.depressionuk.org
13. NHS Choices website. www.nhs.uk
14. Choice and Medication website. www.choiceandmedication.org
2
15. Rethink Mental Illness website. www.rethink.org
33
10/04/2015 08:55
Depression Book 3
16. National Institute for Health and Clinical Excellence. Depression in adults: the treatment

and management of depression in adults (information for the public). www.nice.org.uk
17. Ruoff G. A method that dramatically improves patient adherence to depression treatment.

The Journal of Family Practice 2005;54: 846-852.
18. Feetam CL. Medicine taking behaviour in depression (parts 1 and 2). Progress in Neurology
and Psychiatry 2009;13 (1 and 2). www.progressnp.com
19. Baxter K and Preston CL (editors). Stockleys drug interactions. Tenth edition. London:
Pharmaceutical Press; 2013.
20. Taylor D, Paton C, Kapur S. Prescribing guidelines in psychiatry. Eleventh edition. West
Sussex: Wiley-Blackwell; 2012.
21. Electronic Medicines Compendium. Summary of product characteristics: Sertraline tablets.
www.medicines.org.uk
22. Ultrasis. Beating the blues. http://beatingtheblues.co.uk
23. Linde K, Berner MM, Kriston L. St Johns wort for major depression. Cochrane Database
of Systematic Reviews 2008; (4). DOI: 10.1002/14651858.CD000448.pub3. http://
summaries.cochrane.org/CD000448/st.-johns-wort-for-treating-depression
24. Mental Health Gap Action Programme and World Health Organisation. mhGAP
intervention guide for mental, neurological and substance use disorders in non-specialised settings.
World Health Organisation. 2010.
25. Mayo Clinic. Antidepressants: selecting one thats right for you. www.mayoclinic.org/
diseases-conditions/depression/in-depth/antidepressants/art-20046273
26. Hawton K et al. Toxicity of antidepressants: rates of suicide relative to prescribing and
non-fatal overdose. The British Journal of Psychiatry 2010;196: 354-358. http://bjp.
rcpsych.org/content/196/5/354.full
27. Barnett N, Jubraj B and Varia S. Adherence: are you asking the right questions and taking
the best approach? Pharmaceutical Journal 2013;(291): 153-156.
28. Barnett N. The new medicines service and beyond: taking concordance to the next level.

Pharmaceutical Journal 2011;287: 653.
34
10/04/2015 08:55
Depression Book 3
Notes
35
10/04/2015 08:55
Contacting CPPE

Email
info@cppe.ac.uk
Telephone
0161 778 4000
By post
Oxford Road
Manchester M13 9PT
Share your learning

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Supported by:
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CENTRE FOR PHARMACY

A CPPE focal point programme

CPPE FP_Depression_Book 1.indd 1

CPPE FP_Depression_Book 1.indd 2

Learning with CPPE

About CPPE focal point programmes

About this focal point programme on depression

Checklist for planning

Moving into focus

What do you want to learn?

Reading, practice points and talking points

Checklist for action

Welcome to the pharmacy student edition of CPPE focal point

CPPE FP_Depression_Book 1.indd 3

Learning with CPPE

Core learning (limited expectation of prior knowledge)

Application of knowledge (assumes prior learning)

Continuing professional development (CPD) You can use this

CPPE FP_Depression_Book 1.indd 4

About CPPE focal point programmes

CPPE FP_Depression_Book 1.indd 5

About this focal point programme on

n discuss the condition, choice of medication, duration and withdrawal of

CPPE FP_Depression_Book 1.indd 6

CPPE FP_Depression_Book 1.indd 7

Depression in adults (information for the public) www.nice.org.uk

CPPE FP_Depression_Book 1.indd 8

List three learning needs

Read the whole book

Undertake the practice points

Checklist for planning

I will do this by:

Make notes for the talking points 10 minutes

CPPE FP_Depression_Book 1.indd 9

Moving into focus

2. What are the differences between the presentation and treatment of

3. What are the most common side-effects of SSRIs?

6. How can you differentiate antidepressant discontinuation symptoms

CPPE FP_Depression_Book 1.indd 10

What do you want to learn?

CPPE FP_Depression_Book 1.indd 11

Many people with a chronic physical health problem such as diabetes,

CPPE FP_Depression_Book 1.indd 12

Depression is an illness which is not always easy to define,

CPPE FP_Depression_Book 1.indd 13

CPPE FP_Depression_Book 1.indd 14

The presence of a low mood alone is not sufficient to

1.3 Diagnosis and classification

Reduced concentration and

Reduced self-esteem and

CPPE FP_Depression_Book 1.indd 15

The severity of depression can be diagnosed based on the number of key

Depressed mood for most of the day, nearly every day

Markedly diminished interest or pleasure in all, or almost all,

Significant weight loss when not dieting, or weight gain (a change of

Insomnia or hypersomnia nearly every day

Psychomotor agitation or retardation nearly every day

Fatigue or loss of energy nearly every day

Feelings of worthlessness or guilt nearly every day

Diminished ability to concentrate, or indecisiveness nearly every day

Recurrent thoughts of death, recurrent suicidal ideation, or a plan or

an attempt to commit suicide

CPPE FP_Depression_Book 1.indd 16

In May 2013 the fifth edition of the Diagnostic and

n discuss the condition, choice of medication, duration and withdrawal of

2. What are the differences between the presentation and treatment of

3. What are the most common side-effects of SSRIs?

6. How can you differentiate antidepressant discontinuation symptoms

Significant weight loss when not dieting, or weight gain (a change of

Recurrent thoughts of death, recurrent suicidal ideation, or a plan or

n Metabolic and endocrine disorders (eg, Cushings

n has experienced recent life events, eg, a birth, bereavement, marriage,

n has a history of alcohol/substance misuse or abuse

n Depression should always be considered in a person with any risk

n with a history of moderate or severe depression

n who initially present with sub-threshold depressive symptoms that have

n Switch to a different SSRI or a newer generation antidepressant, which

n Combine antidepressants. By combining

n Sweating, fever, shivering

n Diarrhoea, nausea, vomiting

n Poor co-ordination, confusion, hypomania

n unnecessary treatments may be prescribed to manage the symptoms

n having a negative influence on adherence, possibly adding to a patients

n Lethargy, headache, tremor, sweating, anorexia

n Paraesthesia, numbness, electric shock like sensations

n the severity of the depression

n whether the person has had treatment before and how

n availability of psychological therapies.

n mild to moderate depression, so long as they do not

n mild to moderate depression which has responded inadequately to initial