anxiety and anti-anxiety medications

1. Anxiety and Anti-Anxiety Medications A Presentation for Psychopharmacology Milagros Evardone March 22, 2006

2. (Spielberger & Rickman, 1991)

3. (Spielberger & Rickman, 1991) Normal VS. AbnormalAnxiety �Anxiety is �normal� in any situation in which an immediate danger may result in physical harm.� �Anxiety is also a normal reaction to social-evaluative situations that pose threats to self-esteem 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.�

4. (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.� State anxiety thought to fluctuate over time as a function of perceived threat.State anxiety thought to fluctuate over time as a function of perceived threat.

5. Clinical Disorders (DSM-IV) 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) Anxiety classification contains a heterogeneous group of disorders. Share some symptoms but also have specific symptoms and etiologies. For more information on diagnostic criteria and symptoms, refer to the DSM-IV.Anxiety classification contains a heterogeneous group of disorders. Share some symptoms but also have specific symptoms and etiologies. For more information on diagnostic criteria and symptoms, refer to the DSM-IV.

6. Explanations of Anxiety Psychological theories Freud�s theory Cognitive Behavioral Biological theories Genetics Neural and neuroendocrine pathways involved in body�s normal stress response (fight or flight) Specific action by neurotransmitters and other neurochemicals

7. (Preston et al., 2005) Neural Pathways: Fight or Flight Response

8. (Preston et al., 2005) Neuroendocrine Pathways (Detailed)

9. (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) In individuals with anxiety, may be some dysfunction in this channel system. It has been suggested that individuals with anxiety have a deficiency in an endogenous neurochemical similar to benzodiazepineIn individuals with anxiety, may be some dysfunction in this channel system. It has been suggested that individuals with anxiety have a deficiency in an endogenous neurochemical similar to benzodiazepine

10. (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.

11. (Preston et al., 2005) Etiology of Clinical Disorders Primarily psychogenic GAD Acute stress disorder Specific phobias Agoraphobia Evidence for biological factors Social phobia Anxiety associated with general medical condition Panic disorder - noradrenergic hypothesis some evidence that at least some individuals with GAD have a deficiency in neurochemicals Specific phobias thought to result from age-appropriate fears and conditioned responses. Agoraphobia thought to result from conditioned fear response. Though social phobias are thought to be influenced by psychological factors such as early attachment, development of social skills, interaction with others, there appears to be evidence to suggest a role for the LC. LC may be a key brain structure designed to trigger arousal and distress in infants separated from caregivers and social phobia is viewed as a form of separation. Therefore, it is theorized that those with social phobia have very low thresholds of arousal at the level of the LC accounting for their sensitivity to humiliation, separation, and rejection. Panic Disorder � intense recurring attacks thought to be caused by hypersensitive neurons in the LC or a dysfunction in the inhibitory alpha-2 receptors, the natural braking mechanism of the LC nerve cellssome evidence that at least some individuals with GAD have a deficiency in neurochemicals Specific phobias thought to result from age-appropriate fears and conditioned responses. Agoraphobia thought to result from conditioned fear response. Though social phobias are thought to be influenced by psychological factors such as early attachment, development of social skills, interaction with others, there appears to be evidence to suggest a role for the LC. LC may be a key brain structure designed to trigger arousal and distress in infants separated from caregivers and social phobia is viewed as a form of separation. Therefore, it is theorized that those with social phobia have very low thresholds of arousal at the level of the LC accounting for their sensitivity to humiliation, separation, and rejection. Panic Disorder � intense recurring attacks thought to be caused by hypersensitive neurons in the LC or a dysfunction in the inhibitory alpha-2 receptors, the natural braking mechanism of the LC nerve cells

12. Anti-anxiety Medications (i.e., anxiolytics) Benzodiazepines Atypical benzodiazepines Busipirone Antidepressants Antihistamines Beta blockers Clonidine Tiagabine

13. (Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999) 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. Benzodiazepines indicated for short-term management of acute anxiety, panic disorder, GAD. Benzodiazepines may be inappropriate for elderly because they cause drowsiness and may impair concentration. Benzodiazepines indicated for short-term management of acute anxiety, panic disorder, GAD. Benzodiazepines may be inappropriate for elderly because they cause drowsiness and may impair concentration.

14. (Preston et al., 2005) Atypical Benzodiazepines Benzodiazepine derivatives used as hypnotics. Estazolam (ProSom) Quazepam (Doral) Zolpidem (Ambien) Zaleplon (Sonata) Mechanism: Similar to benzodiazepines. -Estazolam: rapid action, intermediate half-life, no sign.metabolites so no drug accumulation or daytime sedation Quazepam: similar to flurazepam Zolpidem: short-acting, assoc. with less cognitive impairment, and less dependence Zaleplon: 1 hour half-life, low risk-Estazolam: rapid action, intermediate half-life, no sign.metabolites so no drug accumulation or daytime sedation Quazepam: similar to flurazepam Zolpidem: short-acting, assoc. with less cognitive impairment, and less dependence Zaleplon: 1 hour half-life, low risk

15. (Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999) 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. Does not appear useful in treating panic disorder. Less effective in those previously treated with benzodiazepines.Does not appear useful in treating panic disorder. Less effective in those previously treated with benzodiazepines.

16. (Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999) Antidepressants Monoamine oxidase inhibitors (MAO) created in mid 1950�s 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 1950�s � 1980�s - Mechanism: Blocking reuptake of norepinephrine, acetylcholine, and serotonin. - Low therapeutic index. - See table on page 167 of Preston et al., 2005 for drug examples. phenylzine useful in treating panic and other anxiety disorders Parnate may have stimulant effect Imipramine effective in treatment of PD but takes up to 3-5 weeks to work Clomipramine used for treating OCD.phenylzine useful in treating panic and other anxiety disorders Parnate may have stimulant effect Imipramine effective in treatment of PD but takes up to 3-5 weeks to work Clomipramine used for treating OCD.

17. (Arikian & Gorman, 2001; Preston et al., 2005; Walsh, 1999) Antidepressants (cont�) Selective serotonin reuptake inhibitors (SSRI�s) - Introduced in 1980�s - 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. Fluvoxamine used to treat OCD SSRI�s often prescribed for PD, GAD, social phobia, OCD, PTSD, and mixed anxiety and depression Newer anti-depressants: venlafaxine used for GAD, PD, and social phobia, also mirtazapine and nefazodone Fluvoxamine used to treat OCD SSRI�s often prescribed for PD, GAD, social phobia, OCD, PTSD, and mixed anxiety and depression Newer anti-depressants: venlafaxine used for GAD, PD, and social phobia, also mirtazapine and nefazodone

18. (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). Beta blockers have been used with some benefit for PD and social phobia. Beta blockers have brief effect only a few hours.Beta blockers have been used with some benefit for PD and social phobia. Beta blockers have brief effect only a few hours.

19. (Preston et al., 2005) 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.