Generalized anxiety disorder antidepressants

Excessive worry Generalized anxiety disorders Antidepressants, buspirone, benzodiazepines... 

Antidepressants are small heterocyclic molecules entering the circulation after oral administration and passing the blood-brain barrier to bind at numerous specific sites in the brain. They are used for treatment of depression, panic disorders, generalized anxiety disorder, social phobia, obsessive compulsive disorder, and other psychiatric disorders and nonpsychiatric states. 

Antidepressants are considered first-line agents in the management of chronic generalized anxiety disorder. 

Benzodiazepines are recommended for acute treatment of generalized anxiety disorder when short-term relief is needed, as an adjunct during initiation of antidepressant therapy, or to improve sleep. 

Rickels K, Downing R, Schweizer E, Hassman H. (1993). Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry. 50(11) 884-95. 

In recent years many of these primary care cases that would formerly have been seen as anxiety disorders have been portrayed as anxious-depressives and have led to treatment with antidepressants, in particular the more recent serotonin reuptake inhibitors. As part of this rebranding a variety of states such as panic disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder have appeared, along with more traditional disorders such as obsessive compulsive disorder (OCD). Many of these diagnoses are likely to lead to prescriptions of an SSRI although the evidence for benefit from SSRIs is poor except for OCD. 

Escitalopram is manufactured by Forest under the brand name Lexapro, and comes in a 10- or 20-mg tablet. Escitalopram is an antidepressant, but can also be prescribed for generalized anxiety disorder. 

Goa and Ward 1986 Pecknold et al. 1989 Rickels et al. 1982]. In contradistinction to benzodiazepines, the therapeutic effect of buspirone has a lag period similar to that of antidepressants in depression, suggesting that its therapeutic benefits derive from receptor modulation. In addition, buspirone seems to act preferentially in those patients who are not responsive to benzodiazepines, suggesting a possible subgrouping of generalized anxiety disorders. 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

The use of benzodiazepines in anxiety disorders represents a difficult issue because of the well-known addictive properties of this substance class furthermore, the depressogenic lability of benzodiazepines represents a major problem in the treatment of generalized anxiety disorders, in which concomitant depressive symptoms occur in up to 50% of patients [Gulley and Nemeroff 1993 Rickels and Schweizer 1993]. Therefore, a compound mimicking endogenous anxiolytic effects, and that might further possess potential antidepressive properties, is warranted. Neuroactive steroids could represent such a substance class. However, the following issues need to be addressed in this respect ... 

Papadimitriou GN, Kerkhofs M, Kempenaers C, et al EEG sleep in patients with generalized anxiety disorder. Psychiatry Res 26 183-190, 1988 Papadimitriou GN, Christodoulou GN, Katsouyanni K, et al Therapy and prevention of affective illness by total sleep deprivation. J Affect Disord 27 107-116, 1993 Papp M, Muscat R, Willner P Additive effects of chronic treatment with antidepressant drugs and intermittent treatment with a dopamine agonist. Eur Neuropsy-chopharmacol 2 121-125, 1992... 

Generalized anxiety disorder also responds to antidepressant treatment response occurs in approximately 2-3 weeks, but maxi-... 

Rickels K, Downing RW, Schweizer E. Antidepressants in generalized anxiety disorder. Presented at the Annual Meeting of the American Psychiatric Association, Chicago, May 1987. 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

Some of the growth in antidepressant use may be related to the broad application of these agents for conditions other than major depression. For example, antidepressants have received FDA approvals for the treatment of panic disorder, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). In addition, antidepressants are commonly used to treat pain disorders such as neuropathic pain and the pain associated with fibromyalgia. Some antidepressants are used for treating premenstrual dysphoric disorder (PMDD), mitigating the vasomotor symptoms of menopause, and treating stress urinary incontinence. Thus, antidepressants have a broad... 

In addition to its efficacy as a first-line antidepressant, mirtazapine may have enhanced efficacy due to its dual mechanism of action (Fig. 7—3), especially in combination with other antidepressants that block serotonin and/or norepinephrine reuptake. This will be discussed below in the section on antidepressant combinations. Mirtazapine may also have utility in panic disorder, generalized anxiety disorder, and other anxiety disorders, but has not been intensively studied for these indications. 

The serotonin 1A partial agonist buspirone, whose primary use is in generalized anxiety disorder, is also used as a popular augmenting agent for treatment-resistant depression, particularly in North America (serotonin 1A combo in Fig. 7—30). Its potential mechanism of action as an antidepressant augmenting agent is shown in Figures 7—31 to 7—33. 

FIGURE 8-8. In the 1970s and 1980s there began to be an overlap between the use of traditional antidepressants and traditional anxiolytics for treatment of some anxiety disorder subtypes and mixtures of depression and anxiety, but not for generalized anxiety disorder. 

FIGURE 8—10. In the late 1990s the antidepressants venlafaxine XR and others have become first-line treatments for generalized anxiety disorder. Thus, antidepressants are now first-line treatments for both depression and anxiety disorders, rendering the classification of antidepressant versus anxiolytic inappropriate for many antidepressants. 

We have discussed how various antidepressants, especially venlafaxine XR, are being used increasingly for the treatment of generalized anxiety disorder. Buspirone remains a first-line generalized anxiolytic for chronic anxiety, and benzodiazepines are used largely for short-term treatment of intermittent anxiety symptoms. 

Antidepressant drugs, however, might have direct anxiolytic effects. That is, certain antidepressants such as paroxetine (Paxil) or venlafaxine (Effexor) can help reduce anxiety independent of their effects on depression.1,47 These antidepressants have therefore been advocated as an alternative treatment for anxiety, especially for people who cannot tolerate the side effects of traditional anxiolytics, or who might be especially susceptible to the addictive properties of drugs like the benzodiazepines.1,9,46 Moreover, antidepressants such as paroxetine or venlafaxine are now considered effective as the primary treatment for several forms of anxiety, including generalized anxiety disorder, social phobia, and panic disorder.4,29,53 Antidepressants, either used alone or in combination with antianxiety drugs, have become an important component in the treatment of anxiety. 

Kapczinski F, Lima MS, Souza JS, Schmitt R. Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev. 2003 CD003592. 

In addition to the treatment of depression, the Food and Drug Administration (FDA) has approved the (on-label) use of the antidepressants for treatment of panic disorders, obsessive-compulsive disorders, bulimia nervosa, social phobia, and generalized anxiety disorder. And although not the treatment of choice, the tricyclics are sometimes used for enuresis—bed wetting. 

Buspirone may reduce sexual dysfunction associated with generalized anxiety disorder and with serotonergic antidepressants... 

The mood and anxiety disorders in their various permutations constitute a major source of personal suffering and impaired ability to engage in productive Avork and interpersonal relationships. Between 5 and 9% of women and between 2 and 3% of men meet the diagnostic criteria for major depression at any time 10-25% of all women suffer major depression sometime in their lives, while 5-10% of men will develop major depressive disorder (American Psychiatric Association, 1994). The anxiety disorders obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, and generalized anxiety disorder (GAD) show lifetime prevalence rates of approximately 2.5%, 7%, 2.5%, and 5% respectively. Between 3 and 13% of individuals in community samples are regarded to meet the diagnostic criteria for social phobia. Mood and anxiety disorders are common comorbidities (American Psychiatric Association, 1994) and the most common antidepressant medications including the serotonin reuptake inhibitors, the mixed serotonin-catecholamine reuptake inhibitors, the tricyclic antidepressants, and the monoamine oxidase inhibitors, are all effective treatments for anxiety and panic attacks. 

Antidepressants are the agents of choice for long-term management of generalized anxiety disorder. 

Antidepressants have a lag time of 2 to 4 weeks or longer before antianxiety effects occur in generalized anxiety disorder. 

Internal Medicine Review. (1999, November). Antidepressants for general anxiety disorder. Internal Medicine Alert, 2/(21), 164. 

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