Transcript Gender Differences in the Subjective Visual Vertical and the

The Use of SSRIs in the
Treatment of Generalized
Anxiety Disorder.
By: Cameron Thompson
Neuropsychology of Abnormal Behaviour
Outline
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Overview - Generalized Anxiety Disorder (GAD)
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The Neurobiology of GAD
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Pharmacotherapy (Paroxetine)
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Conclusion
SSRIs and Generalized Anxiety Disorder
Overview - GAD
Generalized Anxiety Disorder Involves:
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Chronic and excessive worry about non-specific events or activities.
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Must occur more days than not for at least 6 months, and must be
experienced as difficult to control and intrusive.
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Associated with significant distress and impairment in social and
occupational functioning.
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At a physiological level, it involves a state of chronic over arousal.
SSRIs and Generalized Anxiety Disorder
Prevalence:
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Lifetime prevalence of 5.1% in the United States (Approximately 23
million people).
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Second most frequent psychiatric disorder in the primary care setting.
Impact:
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Impairment equivalent in magnitude to major depression.
Prognosis:
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The course of GAD tends to be chronic and recurrent, with less than one
half of cases remitting without treatment.
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Fortunately, current pharmacological treatments extremely effective
(SSRIs).
SSRIs and Generalized Anxiety Disorder
The Neurobiology of GAD
The Neurobiology of Anxiety:
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Amygdala – Neural structure associated with anxiety.
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Well suited to establishing conditioned fears.
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Thought to influence:
• Autonomic fear responses.
• Cortical interpretation of potentially frightening stimuli.
• Startle reflex.
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Research has demonstrated that damage to these regions in lab animals results
in decreased fear related behaviour.
SSRIs and Generalized Anxiety Disorder
The Neurobiology of GAD (Neural Structures):
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Research has demonstrated that GAD is associated with:
Limbic and Cortical Regions:
• Changes in blood flow in a number of parts of the limbic system and
frontal cortical regions.
Basal Ganglia:
• Increased cortical activity and decreased basal ganglia activity.
Raphe Nucleus:
• Abnormalities in the serotonergic activity of the dorsal and median
raphe nucleus (varied).
SSRIs and Generalized Anxiety Disorder
The Neurobiology of GAD (Neural Structures) Cont…
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Neuroimaging suggests that underlying GAD is a neuronal circuit that
incorporates several areas of the cortex as well as the basal ganglia and
parts of the limbic system and thalamus.
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There is some similarity in the regions associated with GAD and other
disorders, especially depression (ie: Hippocampus).
SSRIs and Generalized Anxiety Disorder
The Neurobiology of GAD (Neurotransmitters):
• Serotonin (5-HT) is highly implicated.
• Activation of 5-HT-sub(2C) receptors within the amygdala found to be
anxiogenic.
• Current research generally suggests that low levels of 5-HT are associated
with GAD.
• However, evidence often contradictory.
• Possibly two forms of anxiety:
• 1) Conditioned anxiety - Targeted to external cues.
• 2) Unconditioned anxiety - Innate fears.
• Some theorize that 5-HT might worsen conditioned anxiety, while
alleviating unconditioned anxiety.
SSRIs and Generalized Anxiety Disorder
Pharmacotherapy
Benzodiazepines:
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Traditionally, anxiety disorders were treated with benzodiazepines.
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Benzodiazepines have a number of disadvantages:
• They have high risks of dependence.
• They do not address the high comorbidity of GAD with depression and
5-HT abnormalities.
Antidepressants:
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In 1993, a major double-blind, placebo-controlled study found that
antidepressants were more effective than benzodiazepines at alleviating
anxiety symptoms in a number of anxiety disorders (tricyclics).
SSRIs and Generalized Anxiety Disorder
SSRIs:
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Correlation between anxiety, 5-HT, and depression led to research into the
use of SSRIs for the treatment of anxiety disorders.
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SSRIs: Block reuptake of serotonin by the presynaptic terminal.
Paroxetine (Paxil):
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The only drug of this class to have been investigated for treatment of GAD
and approved by the Food and Drug Administration (as of 2003).
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Of all antidepressant therapies, paroxetine is licensed for the widest range
of anxiety disorders:
• Obsessive Compulsive Disorder
• Panic Disorder
• Social Anxiety Disorder
• Generalized Anxiety Disorder
• Post-Traumatic Stress Disorder
SSRIs and Generalized Anxiety Disorder
Efficacy (Paroxetine):
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Benzodiazepines show more immediate results (within first two weeks),
however paroxetine shows greater reductions of GAD symptoms by week 4
onwards.
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Patients treated with paroxetine show a significantly greater mean change
from baseline compared with patients taking placebo.
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One study reported a 50% reduction in the severity of GAD symptoms
within 8 weeks.
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Significantly greater rates of remission are achieved relative to placebo.
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Patients with placebo were five times more likely to relapse than patients
on a continuous paroxetine regimen.
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Generally speaking, remission rates increase the longer the course of
treatment.
SSRIs and Generalized Anxiety Disorder
Other Advantages:
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Paroxetine also has the following advantages over many other
pharmacotherapeutic approaches:
• The control of anxiety and co-morbid depression with the use of a
single medication.
• Decreased risk of dependence or withdrawal symptoms.
• More tolerable side effects.
• Reduced interaction potential with alcohol.
• Low lethality in overdose.
SSRIs and Generalized Anxiety Disorder
Tolerability:
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Nausea.
Headache with initial treatment.
Diarrhea.
Initial increase in anxiety.
Sedation.
Sweating.
Small blood pressure elevations.
Modest weight gain.
Sexual dysfunction.
SSRIs and Generalized Anxiety Disorder
Other disadvantages:
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Many patients expect immediate improvement, and discontinue treatment
before paroxetine can exert its effects.
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They typically take two to three weeks to take effect.
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Overall, benzodiazepines have the most rapid effects.
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The relapse rate following discontinuation is considerable.
SSRIs and Generalized Anxiety Disorder
• SSRIs are inhibitors of hepatic cytochrome p450 isoenzymes. As a result,
SSRIs drive up the blood levels of other medications metabolized by these
isoenzymes. Can affect the metabolism of tricyclics and neuroleptics.
• SSRI discontinuation syndrome:
• Can occur during or following discontinuation of regular SSRI use.
• Often begins between 24 hours to one week.
• SSRIs are not addictive in the conventional sense, but sudden
discontinuation is known to produce both somatic and psychological
symptoms:
 Sexual dysfunction.
 Paresthesia.
SSRIs and Generalized Anxiety Disorder
Conclusion
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SSRIs generally, and paroxetine specifically, are highly effective and well
tolerated pharmacological treatment options for GAD.
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They have proven effective at encouraging remission, preventing relapse,
and ameliorating co-morbid depressive symptoms.
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They improve the working, social, and family life experienced by sufferers.
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The length of time required for SSRIs to take effect, however, indicates the
need for temporary use of fast-acting medications, such as
benzodiazepines.
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The mechanisms which underlie GAD, including 5-HT, are still relatively
obscure, and further research is required to elucidate them.
SSRIs and Generalized Anxiety Disorder
Questions
SSRIs and Generalized Anxiety Disorder