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Many depressed patients follow a recurring course of episodic illness, often with lesser levels of symptoms and disability between major episodes, and therefore merit consideration of long-term maintenance medication to reduce the risk of recurrence. Such treatment has been tested for as long as 5 years, using relatively high doses of imipramine, with evidence that early dose reduction led to a higher risk of relapse. Long-term supplementation of an antidepressant with lithium may enhance the result. Prolonged maintenance treatment of patients with recurring major depression for more than a year has rarely been evaluated with modem antidepressants, and long-term dose-response data with any antidepressant are very limited. The use of indefinitely prolonged maintenance treatment with an antidepressant is guided by the history of multiple, and especially severe or life-threatening, recurrences and the impression that recurrence risk is greater in older patients. Because rapid discontinuation or sharp reduction in doses of antidepressants and lithium may contribute to excess early recurrence of illness, gradual reduction and close clinical follow-up over at least several weeks are recommended when maintenance treatment is to be discontinued and when stopping continuation therapy within the months following recovery from an acute episode of depression.

PHARMACOTHERAPY OF ANXIETY

Anxiety is a symptom of many psychiatric disorders and an almost ineviOrder Buspar online US component of many medical and surgical conditions. Symptoms of anxiety commonly are associated with depression and especially with dysthymic disorder (chronic depression of moderate severity), panic disorder, agoraphobia and other specific phobias, obsessive-compulsive disorder, eating disorders, and many personality disorders. Sometimes, no treaOrder Buspar online US primary illness is found, or if one is found and treated, it may be desirable to deal directly with the anxiety at the same time. In such situations, antianxiety medications are frequently and appropriately used.

Currently, the benzodiazepines and the SSRIs are the most commonly employed pharma-cotherapies for common clinical anxiety disorders (see Generic Buspar 16). Benzodiazepines sometimes are given to patients presenting with anxiety mixed with symptoms of depression, although their efficacy in altering the core features of severe major depression has not been demonstrated.

The most favorable responses to the benzodiazepines are obtained in situations that involve relatively acute anxiety reactions in medical or psychiatric patients who have either modifiable primary illnesses or primary anxiety disorders. However, this group of anxious patients also has a high response rate to placebo and is likely to undergo spontaneous improvement. Antianxiety drugs also are used in the management of more persistent or recurrent primary anxiety disorders. A particularly controversial aspect of the use of benzodiazepines, especially those of high potency, is in long-term management of patients with sustained or recurring symptoms of anxiety; despite clinical [Buy Buspar 10 mg Tablets] benefit for at least several months, it is unclear if the long-term benefits can be distinguished from nonspecific (“placebo”) effects following development of tolerance on the one hand, or prevention of related withdrawal-emergent anxiety on the other.

The antihistamine hydroxyzine is an effective antianxiety agent, but only at doses (-400 mg/day) that produce marked sedation (see Generic Buspar 24). Propranolol and metoprolol, lipophilic fi adren-ergic receptor antagonists that enter the CNS, can reduce the autonomic symptoms (nervousness and muscle tremor) associated with specific situational or social phobias but do not appear to be effective in generalized anxiety or panic disorder (see Generic Buspar 10). Similarly, other antiadrener-gic agents, including clonidine, may modify autonomic expression of anxiety but are not demon-strably useful in the treatment of severe anxiety disorders.

The azapirones (azaspirodecanediones) (e.g.,buspirone [BUSPAR]) are useful in anxiety ordys-phoria of moderate intensity. The azapirones have limited antidopaminergic actions in vivo, do not induce clinical extrapyramidal side effects, and do not interact with binding sites for benzodi-azepines or facilitate the action of GABA. They are not anticonvulsant (and may even lower seizure threshold slightly), do not appear to cause tolerance or withdrawal reactions, and do not show cross-tolerance with benzodiazepines or other sedatives. Buspirone and several experimental congeners (e.g., gepirone, ipsapirone, and tiospirone) have selective affinity for 5-HT receptors of the 5-HT]A type, for which they appear to be partial agonists (see Generic Buspar 11). Buspirone lacks beneficial actions in severe anxiety with panic attacks. The risk of suicide with buspirone is very low.

OTHER THERAPEUTIC USES OF THESE DRUGS The various antidepressant agents have found broad utility in other disorders that may not be related psychobiologically to the mood disorders. Current applications include rapid but temporary suppression of enuresis with low (e.g., 25 mg) pre-bedtime doses of tricyclic antidepressants, including imipramine and nor-triptyline, by uncertain mechanisms in children and in geriatric patients, as well as a beneficial effect of duloxetine on urinary stress incontinence. Antidepressants have a growing role in attention-deficit/hyperactivity disorder in children and adults, for which imipramine, desipramine, and nortriptyline appear to be effective, even in patients responding poorly to or who are intolerant of the stimulants (e.g., methylphenidate). Newer NE selective reuptake inhibitors also may be useful in this disorder; atomoxetine is approved for this application. Utility of SSRIs in this syndrome is not established, and bupropion, despite its similarity to stimulants, appears to have limited efficacy.

Antidepressants tend to provide a more sustained and continuous improvement of the symptoms of attention-deficit/hyperactivity disorder than do the stimulants and do not induce tics or other abnormal movements sometimes associated with stimulants. Indeed, desipramine and nortriptyline may effectively treat tic disorders, either in association with the use of stimulants or in patients with both attention deficit disorder and Tourette’s syndrome. Antidepressants also are leading choices in the treatment of severe anxiety disorders, including panic disorder with agoraphobia, generalized anxiety disorder, social phobia, and obsessive-compulsive disorder, as well as for the common comorbidity of anxiety in depressive illness. Antidepressants, especially SSRIs, also are employed in the management of posttraumatic stress disorder, which is marked by anxiety, startle, painful recollection of the traumatic events, and disturbed sleep.

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