Dr. Clayton is professor of psychiatric medicine at the University of Virginia in Charlottesville.
Disclosure: Dr. Clayton receives grants from Bayer, Boehringer-Ingelheim, Eli Lilly, Forest, GlaxoSmithKline, Organon, Pfizer, Pharmacia, Pherin, and Merck; is a consultant for Bayer, Boehringer-Ingelheim, Eli Lilly, GlaxoSmithKline, Pharmacia, and Vela; and is on the Speaker’s Bureau of Bristol-Myers Squibb, GlaxoSmithKline, Organon, and Pfizer.
Anxiety disorders may be classified in the following three ways:
Changes in sex hormones associated with reproductive life events may also contribute to onset or exacerbation of anxiety symptoms. Allopregnanolone, a progesterone metabolite, enhances GABA tone and causes subsequent antianxiety effects.9 However, progesterone increases monamine oxidase (MAO) activity, which may cause dysregulation of neurotransmitters leading to anxiety and/or affective disturbance. Thus, in some women (especially those with panic disorder), when progesterone levels drop, anxiety may increase. Levels may drop during the late luteal phase of the menstrual cycle, postpartum,10 during the menopausal transition, or with abrupt cessation of ovarian function; the latter may occur with the use of ovarian suppressants11 or after surgical menopause.
Interestingly, anxiety symptoms during pregnancy follow the one-quarter rule: 25% of women will experience improvement, 50% will not have a significant change, and 25% will demonstrate worsening of anxiety symptoms.10 Anxiety and/or depressive symptoms often herald the onset of other perimenopausal symptoms, such as hot flashes, subsequent sleep disturbance, and fatigue. Hypothalamic-pituitary-ovarian hormones are usually within the normal range at this time; however, diagnosis and treatment of the anxiety disorder may reduce other symptoms of the menopausal transition, such as hot flashes.12
Low-dose atypical antipsychotics have been used in addition to antidepressants in patients with treatment-resistant anxiety disorders. Buspirone may also be useful in the treatment of generalized anxiety disorder, and as an adjunctive agent in the treatment of obsessive-compulsive disorder and social anxiety disorder.13
Individuals with anxiety disorders are more sensitive to the side effects of all medications and may misinterpret side effects as a worsening of the disorder; thus, it is crucial that patients understand the process of treatment. Difficulties experienced early in treatment or with dose increases are due to acute adverse events that subside over time, while the therapeutic benefit of the medication treatment may not be realized until higher doses are tolerated for 4–6 weeks. As such, medication therapy in patients with anxiety symptoms must be initiated at the lowest possible dose; dosage increases should occur only after the acute adverse events have subsided, which may take up to 2 weeks in anxious patients. Thus, it may take many weeks to months to achieve an appropriate therapeutic dose, which is usually higher than doses required to treat depression.
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