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Psychotherapeutic Agents

Antidepressants
and Antipsychotics

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Psychotherapeutics

• The therapy of emotional and mental


disorders

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Psychotherapeutics

• Anxiety
• Grief
• Depression

are normal human emotions

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Psychotherapeutics

• The ability to cope with these emotions can


range from occasional depression or anxiety
to constant emotional distress to the point
ofinterfering with the ability to carry on
normal daily living.

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Psychotherapeutics

• When these emotions significantly affect an


individual’s ability to carry out normal daily
functions, treatment with a psychotherapeutic
drug is a possible option.

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Psychotherapeutics

Three main emotional and mental disorders:


• Psychoses
• Affective disorders
• Anxiety

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Psychotherapeutics

Psychosis
• A major emotional disorder that impairs the mental
function of the affected individual to the point that
the individual cannot participate in everyday life.
• Hallmark: loss of contact with reality

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Psychotherapeutics

Affective Disorders
• Major emotional disorders that impair the
mental function of the affected individual to
the point that the individual cannot
participate in everyday life.

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Psychotherapeutics

Affective Disorders
• Mania: abnormally pronounced emotions
• Depression: abnormally reduced emotions
• Bipolar affective disorder: exhibits both mania
and depression

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Psychotherapeutics

Pathophysiology
Biochemical Imbalance
• Mental disorders are associated with abnormal
levels of endogenous chemicals, such as
neurotransmitters, in the brain.

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Psychotherapeutics

Pathophysiology
Biochemical Imbalance
• Brain levels of certain catecholamines play an
important role in maintaining mental health.
– Dopamine
– Serotonin
– Histamine

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Psychotherapeutics

Pathophysiology
Biochemical Imbalance
• Other biochemicals are necessary for normal
mental function.
– GABA
– acetylcholine
– lithium

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Etiology of Depression

Biogenic Amine Hypothesis


• Depression and mania are due to an alteration in
neuronal and synaptic catecholamine concentration
at adrenergic receptor sites in the brain.
– Depression: deficiency of catecholamine,
especially norepinephrine
– Mania: excess amines

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Instructors may wish to insert
EIC Image #45:

Biogenic Amine Hypothesis

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Affective Disorders

Drug Categories
• Antidepressants
• tricyclics, tetracyclics, SSRIs, MAOIs
• Antimanic Agents
• lithium

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Antidepressants

Cyclic antidepressants
– tricyclics
– tetracyclics
• Monoamine oxidase inhibitors (MAOIs)
• Second-generation antidepressants
and SSRIs

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Cyclic Antidepressants

• Tricyclic antidepressants—primary:
amitriptyline (Elavil), doxepin (Sinequan),
imipramine (Tofranil)
• Tricyclic antidepressants—secondary:
desipramine (Norpramin), nortriptyline
(Aventyl), protriptyline (Vivactil)
• Tetracyclic antidepressants:
amoxapine (Asendin), maprotiline (Ludiomil)

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Cyclic Antidepressants
Mechanism of Action
• Block reuptake of neurotransmitters, causing
accumulation at the nerve endings.
• It is thought that increasing concentrations of
neurotransmitters will correct the abnormally
low levels that lead to depression.

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Cyclic Antidepressants
Mechanism of Action—Drug Effects
Blockade of norepinephrine:
– antidepressant, tremors, tachycardia, additive
pressor effects with sympathomimetic drugs

Blockade of serotonin:
– antidepressant, nausea, headache, anxiety,
sexual dysfunction

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Cyclic Antidepressants
Therapeutic Uses
• Depression
• Childhood enuresis (imipramine)
• Obsessive-compulsive disorders
(clomipramine)
• Adjunctive analgesics
• Trigeminal neuralgia

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Cyclic Antidepressants
Side Effects
• Sedation
• Impotence
• Orthostatic hypotension
• Older patients:
– dizziness, postural hypotension, constipation,
delayed micturation, edema, muscle tremors

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Tricyclic Antidepressants Overdose

• Lethal—70 to 80% die before reaching


the hospital
• CNS and cardiovascular systems are
mainly affected
• Death results from seizures or dysrhythmias
• No specific antidote
– Decrease drug absorption with activated charcoal
– Speed elimination by alkalinizing urine
– Manage seizures and dysrhythmias
– Basic life support
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Antidepressants
Monoamine Oxidase Inhibitors: MAOIs
• Highly effective
• Considered second-line treatment for
depression not responsive to cyclics
• Disadvantage: potential to cause
hypertensive crisis when taken with tyramine

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Antidepressants: MAOIs

• phenelzine (Nardil)
• tranylcypromine (Parnate)
• isocarboxazid (Marplan)

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Antidepressants: MAOIs
Mechanism of Action
• Inhibit the MAO enzyme system in the CNS
• Amines (dopamine, serotonin,
norepinephrine) are not broken down,
resulting in higher levels in the brain
• Result: alleviation of symptoms of
depression

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Antidepressants: MAOIs
Therapeutic Uses
• Depression, especially types characterized
by reverse vegetative symptoms such as
increased sleep and appetite
• Depression that does not respond to other
agents such as tricyclics

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Antidepressants: MAOIs
Side Effects
• Few side effects—orthostatic hypotension
most common
Tachycardia Palpitations
Dizziness Drowsiness
Insomnia Headache
Anorexia Nausea
Blurred vision Impotence

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Antidepressants: MAOIs
Overdose
• Symptoms appear 12 hours after ingestion
• Tachycardia, circulatory collapse,
seizures, coma
• Treatment: protect brain and heart,
eliminate toxin
– Gastric lavage
– Urine acidification
– Hemodialysis

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Antidepressants: MAOIs
Hypertensive Crisis and Tyramine
• Ingestion of foods and/or drinks with
the amino acid TYRAMINE leads to
hypertensive crisis, which may lead
to cerebral hemorrhage, stroke,
coma, or death

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Antidepressants: MAOIs
Hypertensive Crisis and Tyramine
Avoid foods that contain tyramine!
• Aged, mature cheeses (cheddar, blue, Swiss)
• Smoked/pickled or aged meats, fish, poultry
(herring, sausage, corned beef, salami, pepperoni,
paté)
• Yeast extracts
• Red wines (Chianti, burgundy, sherry, vermouth)
• Italian broad beans (fava beans)
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Second-Generation Antidepressants

• Newer
• Fewer side effects than tricyclics, but not
superior in overall efficacy or onset of action
– trazodone (Desyrel)
– bupropion (Wellbutrin, Zyban)
– selective serotonin reuptake inhibitors (SSRIs)

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Second-Generation
Antidepressants and SSRIs
Mechanism of Action
• Selectively inhibit serotonin reuptake
• Little or no effect on norepinephrine or
dopamine reuptake
• Results in increased serotonin
concentrations at nerve endings
Advantage over tricyclics and MAOIs:
Little or no effect on cardiovascular system
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Second-Generation Antidepressants
Therapeutic Uses
• Used for depression—very few serious side effects
• Bipolar affective disorder
• Obesity
• Eating disorders
• Obsessive-compulsive disorder
• Panic attacks
• Myoclonus
• Treatment of various substance abuse problems
(bupropion [Zyban] is used for smoking cessation
treatment)
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Second-Generation Antidepressants
Side Effects
Body System Effects
CNS Headache, dizziness,
tremor, nervousness,
insomnia, fatigue
GI Nausea, diarrhea,
constipation, dry mouth
Other Sweating, sexual
dysfunction

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Second-Generation Antidepressants
Drug Interactions
• Highly bound to plasma proteins
• Compete with other protein-binding drugs,
resulting in more free, unbound drug to
cause a more pronounced drug effect

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Antipsychotics

• Drugs used to treat serious mental illness


• Behavioral problems or psychotic disorders

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Antipsychotics

• Thioxanthenes: chlorprothixene, thiothixene


(Navane)
• Butyrophenones: haloperidol (Haldol)
• Dihydroindolones: molindone (Moban)
• Dibenzoxazepine: loxapine (Loxitane)
• Phenothiazines: three structural groups

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Antipsychotics
Phenothiazine Structural Groups
• Aliphatic: chlorpromazine (Thorazine),
triflupromazine (Vesprin)
• Piperidine: mesoridazine (Serentil),
thioridazine (Mellaril)
• Piperazine: fluphenazine (Prolixin),
perphenazine (Trilafon), prochlorperazine
(Compazine), trifluoperazine (Stelazine)
Largest group of psychotropic agents
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Antipsychotics
Atypical Antipsychotics
• clozapine (Clozaril)
• risperidone (Risperdal)
• olanzapine (Zyprexa)
• quetiapine (Seroquel)

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Antipsychotics: Mechanism of Action

• Block dopamine receptors in the brain


(limbic system, basal ganglia)—areas
associated with emotion, cognitive function,
motor function
• Dopamine levels in the CNS are decreased
• Result: tranquilizing effect in psychotic
patients

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Antipsychotics: Mechanism of Action

• The newer, atypical antipsychotics also block


specific serotonin receptors (serotonin-2
[5HT2] receptors).
• This is responsible for their improved
efficacy and safety profiles.

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Antipsychotics: Drug Effects

• Block dopamine receptors in CNS


• Block alpha receptors (causing hypertension,
other cardiovascular effects)
• Block histamine receptors (causing
anticholinergic effects)
• Block serotonin
• Also function as antiemetics
• Antianxiety effects
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Antipsychotics: Therapeutic Uses

• Treatment of serious mental illnesses:


– Bipolar affective disorder
– Depressive and drug-induced psychoses
– Schizophrenia
– Autism
• Movement disorders (such as Tourette’s
syndrome)
• Some medical conditions
– Nausea, intractable hiccups
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Antipsychotics: Side Effects

Body System Effects


CNS Sedation, delirium
Cardiovascular Orthostatic hypotension,
syncope, dizziness,
ECG changes
Dermatologic Photosensitivity, skin rash,
hyperpigmentation, pruritus

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Antipsychotics: Side Effects

Body System Effects


GI Dry mouth, constipation
GU Urinary hesitancy or
retention, impaired erection
Hematologic Leukopenia and
agranulocytosis
Metabolic/endocrine Galactorrhea, irregular
menses
increased appetite,
polydipsia
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Psychotherapeutic Agents:
Nursing Implications
• Before beginning therapy, assess both the
physical and emotional status of patients
• Obtain baseline VS, including postural BP
readings
• Obtain liver and renal function tests (and
baseline platelet levels for MAOIs)

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Psychotherapeutic Agents:
Nursing Implications
• Assess for possible contraindications to
therapy, cautious use, and potential drug
interactions
• Assess LOC, mental alertness, potential
for injury to self and others
• Check the patient’s mouth to make sure
oral doses are swallowed

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Psychotherapeutic Agents:
Nursing Implications
• Provide simple explanations about the drug,
its effects, and the length of time before
therapeutic effects can be expected
• Abrupt withdrawal should be avoided
• Advise patients to change positions slowly
to avoid postural hypotension and possible
injury

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Psychotherapeutic Agents:
Nursing Implications
• The combination of drug therapy and
psychotherapy is emphasized because
patients need to learn and acquire more
effective coping skills
• Only small amounts of medications should
be dispensed at a time to minimize the risk
of suicide attempts
• Simultaneous use of these agents with
alcohol or other CNS depressants can
be fatal
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Psychotherapeutic Agents:
Nursing Implications
Antidepressants
• Many cautions, contraindications, and interactions
exist pertaining to the use of antidepressants.
• Inform patients that it may take 1 to 3, even 4,
weeks to see therapeutic effects.
• Monitor patients closely during this time and
provide support.

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Psychotherapeutic Agents:
Nursing Implications
Antidepressants
• Sedation often occurs with tricyclic therapy; notify
physician if this lasts more than 2 weeks.
• Assist elderly or weakened patients with ambulation
and other activities as falls may occur due to
drowsiness or postural hypotension.

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Psychotherapeutic Agents:
Nursing Implications
Antidepressants
• Tricyclics may need to be weaned and discontinued
before undergoing surgery to avoid interactions with
anesthetic agents.
• Monitor for side effects and discuss with patients.
• Encourage patients to wear medication ID badges
naming the agent being taken.

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Psychotherapeutic Agents:
Nursing Implications
Antidepressants
• Caffeine and cigarette smoking may decrease
effectiveness of medication therapy
• Instruct patients and family regarding tyramine-
containing foods and signs and symptoms of
hypertensive crisis

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Psychotherapeutic Agents:
Nursing Implications
Antipsychotics—Phenothiazines
• Instruct patients to wear sunscreen due to
photosensitivity
• Avoid taking antacids or antidiarrheal preparations
within 1 hour of a dose
• Do not take alcohol or other CNS depressants
with these medications

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Psychotherapeutic Agents:
Nursing Implications
Antipsychotics—Phenothiazines
• Long-term haloperidol therapy may result in tremors,
nausea, vomiting, or uncontrollable shaking of small
muscle groups; these symptoms should be reported
to the physician
• Oral forms may be taken with meals to decrease
GI upset
• These agents may cause drowsiness, dizziness, or
fainting; instruct patients to change positions slowly

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Psychotherapeutic Agents:
Nursing Implications
Monitor for therapeutic effects:
• Monitor mental alertness, cognition, affect,
mood,ability to carry out activities of daily
living, appetite, and sleep patterns
• Monitor the patient’s potential for self-injury
during the delay between the start of therapy
and symptomatic improvement

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Psychotherapeutic Agents:
Nursing Implications
Monitor for therapeutic effects
• For antidepressants:
– Improved sleep patterns and nutrition, increased
feelings of self-esteem, decreased feeling of
hopelessness, increased interest in self and
appearance, increased interest in daily activities,
fewer depressive manifestations or suicidal
thoughts or ideations

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Psychotherapeutic Agents:
Nursing Implications
Monitor for therapeutic effects
• For antipsychotics:
– Improved mood and affect, alleviation of
psychotic symptoms and episodes
– Decrease in hallucinations, paranoia, delusions,
garbled speech, inability to cope

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

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