Anxiety and Anti-Anxiety Medications

A Presentation for Psychopharmacology Milagros Evardone March 22, 2006

What is anxiety?
Anxiety has been defined as an unpleasant emotional state or reaction that can be distinguished from others, such as anger or grief, by a unique combination of experiential qualities and physiological changes.
An anxiety state consists of feelings of tension, apprehension, nervousness, and worry, and activation of the autonomic nervous system.

Physiological manifestations generally include increased blood pressure, rapid heart rate, sweating, dryness of mouth, vertigo, irregularities in breathing, and muscular skeletal disturbances.
(Spielberger & Rickman, 1991)

Normal VS. Abnormal Anxiety

Anxiety is normal in any situation in which an immediate danger may result in physical harm.
Anxiety is also a normal reaction to socialevaluative situations that pose threats to selfesteem or psychological well-being. Neurotic, clinical, or abnormal anxiety occurs in situations in which there is no real physical or psychological danger, or when the emotional reaction is disproportionate in intensity to the actual danger.
(Spielberger & Rickman, 1991)

More Anxiety Definitions

State anxiety A temporal cross-section in the emotional stream of life of a person, consisting of tension, apprehension, nervousness, and worry and activation (arousal) of the autonomic nervous system.
Trait anxiety Relatively stable individual differences in anxiety-proneness, that is, differences between individuals in the tendency to perceive stressful situations as dangerous or threatening.
(Spielberger & Rickman, 1991)

Clinical Disorders (DSMIV)

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. Panic disorder (PD) with or without agoraphobia Agoraphobia without history of PD Specific phobia Social phobia Obsessive-compulsive disorder (OCD) Posttraumatic stress disorder (PTSD) Acute stress disorder Generalized anxiety disorder (GAD) Anxiety disorder due to a general medical condition Substance-induced anxiety disorder Anxiety disorder NOS

*(For more information on diagnostic criteria and symptoms, refer to www.adaa.org and www.nimh.nih.gov/healthinformation/anxietymenu.cfm)

Explanations of Anxiety
Psychological theories
1. Freuds theory 2. Cognitive 3. Behavioral

Biological theories
1. Genetics 2. Neural and neuroendocrine pathways involved in bodys normal stress response (fight or flight) 3. Specific action by neurotransmitters and other neurochemicals

Neural Pathways: Fight or Flight Response

Stressful Event Cortex

Amygdala Locus coeruleus

Hypothalamus Sympathetic nervous system Pituitary Adrenal medulla Adrenal cortex Thyroid

Cortisol

Thyroxin

Adrenaline

Noradrenaline

(Preston et al., 2005)

Neuroendocrine Pathways (Detailed)

Amygdala
Hypothalamus

Parabrachial Nucleus

Periaquaductal Gray Area

Locus Coeruleus

CRF

TRH SNS

Inc. respiration

Freeze, Avoid, Escape

(NE)* Inc. alertness

Pituitary

Pituitary

ACTH

TSH Adrenal Medulla NE* Through out the body

Adrenal Cortex

Thyroid Gland

Adrenaline

NE*

Cortisol

T3

T4

(Preston et al., 2005)

Gamma-aminobutyric acid (GABA)

GABA plays a role in activating chloride ion channels. Chloride ions (- charge) come into the cell and hyperpolarize the cell. This results in calming of overall brain excitation.
(see diagram on p. 103 of Preston et al., 2005)

(Preston et al., 2005)

Serotonin
Excitability of locus coeruleus (LC) also mediated by serotonin. Global decrease in serotonin thought to affect LC causing it to become disinhibited (i.e., more sensitive to activation) Serotonin also hypothesized to inhibit cellular reactivity in the amygdala.
(Preston et al., 2005)

Etiology of Clinical Disorders

Primarily psychogenic
1. GAD 2. Acute stress disorder 3. Specific phobias 4. Agoraphobia

Evidence for biological factors

1. Social phobia 2. Anxiety associated with general medical condition 3. Panic disorder
- noradrenergic hypothesis

(Preston et al., 2005)

Anti-anxiety Medications (i.e., anxiolytics)

Benzodiazepines Atypical benzodiazepines Busipirone Antidepressants Antihistamines Beta blockers Clonidine Tiagabine

Benzodiazepines
First drug of this type (Librium) created in 1957. Mechanism: Interact with benzodiazepine receptors and enhance the effect of GABA, increasing influx of chloride ions. Rapid effect within 30 minutes; Therapeutic effect within 1 week Relatively short half-lives (see table on p. 190 of Preston et al., 2005) 75% of users show moderate to marked improvement in symptoms Mild and transient side effects May become physically addictive and lead to withdrawal symptoms if discontinued abruptly.
(Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999)

Atypical Benzodiazepines
Benzodiazepine derivatives used as hypnotics.
1. 2. 3. 4. Estazolam (ProSom) Quazepam (Doral) Zolpidem (Ambien) Zaleplon (Sonata)

Mechanism: Similar to benzodiazepines.

(Preston et al., 2005)

Busipirone
Type: azapirone drug Mechanism: Acts on 5-HT 1A receptor; thought to balance serotonin levels by lowering them in anxious persons. However, exact mechanism unknown. Delayed effect Therapeutic effect within one or two weeks. Appears particularly effective in treatment of GAD. Not addictive. Does not produce psychomotor impairment and does not interact with other CNS depressants.

(Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999)

Antidepressants

Monoamine oxidase inhibitors (MAO) created in mid 1950s

MAO inhibitors not frequently prescribed today due to interaction with tyramine and the associated food restrictions. Low therapeutic index. See table on page 167 of Preston et al., 2005 for drug examples.

Cyclic drugs
- Most prescribed from 1950s 1980s - Mechanism: Blocking reuptake of norepinephrine, acetylcholine, and serotonin. - Low therapeutic index. - See table on page 167 of Preston et al., 2005 for drug examples.

(Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999)

Antidepressants (cont)
Selective serotonin reuptake inhibitors (SSRIs)
- Introduced in 1980s - More potent than cyclic drugs. - Long half-life. - Bigger therapeutic index and fewer side effects. - See table on page 167 of Preston et al., 2005 for drug examples.
(Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999)

Other Anti-Anxiety Agents

Antihistamines
Mechanism: Block histamine receptors in the CNS associated with anxiety and agitation. Rapid effect within 20-30 min. May cause drowsiness, impaired performance, and develop tolerance to anxiolytic effects.

Beta Blockers
Mechanism: Block the effects of norepinephrine at the receptor in the brain and the peripheral nervous system. Originally developed to treat hypertension. Effective at reducing physical symptoms of anxiety (i.e., rapid heart beat, muscle tension, dry mouth).

(Preston et al., 2005; Walsh, 1999)

Other Anti-Anxiety Agents

Clonidine
Mechanism: alpha-2 adrenergic agonist; presynaptic inhibitor of norepinephrine release Originally used to treat hypertension

Tiagabine
Mechanism: GABA reuptake inhibitor Originally an anticonvulsant May be useful in treating PTSD and PD.

(Preston et al., 2005)

From www.healthyplace.com/Communities/Anxiety/treatment/medications.asp