Buspirone therapy in anxious elderly patients: a controlled clinical trial.

Forty patients over 65 years of age with anxiety symptoms due to an anxiety state (N = 20) or secondary to neurotic depression (N = 20) took part in a double-blind, placebo-controlled trial conducted in a primary care practice. All patients were receiving concomitant drug therapy for chronic medical conditions; 70% were receiving two or more nonpsychotropic drugs in addition to the study medication. Patients were randomly assigned to treatment with buspirone 5-30 mg/day or placebo for 4 weeks, with clinical evaluations made weekly. One buspirone-treated and two placebo-treated patients discontinued treatment after 2 weeks because of lack of efficacy. Buspirone treatment resulted in significantly greater (p less than or equal to 0.05) improvement on the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression assessment than did placebo. Mild adverse experiences were reported by five buspirone-treated and nine placebo-treated patients. Buspirone (mean dose, 18 mg/day) proved equally effective for elderly patients suffering anxiety states or neurotic depression at doses similar to those used in younger patients, and was well tolerated by elderly patients receiving treatment for other chronic medical conditions.

Clinical effects of the 5-HT1A partial agonists in depression: a composite analysis of buspirone in the treatment of depression.

The azapirone class of anxiolytic drugs is being evaluated for clinical use in the treatment of depression. Buspirone, a serotonin (5-hydroxytryptamine, 5-HT) partial agonist active at the 5-HT1A receptor subtype, was evaluated in the treatment of depression in a series of five placebo-controlled, parallel group studies involving 382 patients with DSM-III major depression and significant associated anxiety symptoms (both Hamilton depression [HAM-D] and Hamilton anxiety [HAM-A] scales greater than or equal to 18). Buspirone therapy was initiated at 15 mg/day with individual dose titration to a maximum of 90 mg/day and resulted in marked improvement in both depressive and anxiety symptoms. Analyses of the composite data base from the five studies show significant (p less than 0.05) improvement in mean HAM-D, HAM-A, and Clinical Global Impression-Global Improvement scale ratings for buspirone-treated compared with placebo-treated patients. Of particular interest was significant improvement in cardinal depression symptoms, e.g., depressed mood, guilt, work and interest, anergia, and diurnal variation of mood. Subset analyses revealed that patients with melancholic-type major depression and patients with more severe symptoms (judged by higher initial HAM-D or HAM-A total scores) responded better to buspirone than did patients who were less ill. The buspirone dose most frequently associated with clinically significant improvement was 40 mg/day. Gepirone, an analogue of buspirone with highly selective binding affinity for the 5-HT1A receptor subtype, also shows promise of antidepressant efficacy in preliminary controlled clinical trials. These data suggest that azapirones, which as partial agonists modulate 5-HT1A receptor function, have clinically important antidepressant properties.

A double-blind comparison of buspirone, clobazam, and placebo in patients with anxiety treated in a general practice setting.

Sixty patients being treated for anxiety in a primary care facility received (double-blind) buspirone, the benzodiazepine drug clobazam, or placebo for 3 weeks. The mean daily dose at the end of treatment was 23 mg for buspirone and 21 mg for clobazam. Patients were assessed weekly using the Hamilton Rating Scale for Anxiety and Clinical Global Impression scale. Both active treatments produced significant improvement in anxiety symptoms compared with placebo as early as the first week of treatment, and there was progressive improvement over the subsequent 2 weeks. Response to buspirone was equally favorable in anxious patients who experienced depressive symptomatology.

Serotonergic anxiolytics and treatment of depression.

The serotonin 5-hydroxytryptamine-1A (5-HT1A) receptor agonists buspirone and gepirone have effects on serotonergic systems, including presynaptic and postsynaptic receptors, that predict both anxiolytic and antidepressant activity. Chronic administration of both drugs produces a down-regulation of 5-HT2 receptors, a finding common to most antidepressant drugs irrespective of mechanism of action. In addition, gepirone induces a full-blown serotonin syndrome in rodents and is active in the behavioral despair test mediated by an action on serotonergic neurons. Buspirone is active in this paradigm when injected directly into the serotonergic dorsal raphe nucleus. The therapeutic effects of both buspirone and gepirone have been assessed in placebo-controlled studies of patients with major depression. Findings in these studies support antidepressant efficacy in addition to anxiolysis. In double-blind studies of patients with major depression treated for 8 weeks, each drug was found to be superior to placebo in improvement in Hamilton Depression and Anxiety total scores as well as individual depressive symptoms. These clinical findings are consistent with preclinical pharmacology suggesting that 5-HT1A partial agonists may possess intrinsic antidepressant activity.

Buspirone in Parkinson's disease.

Buspirone, an anxiolytic unrelated to benzodiazepines that may act at the presynaptic dopamine receptor, was given to 11 patients with Parkinson's disease in an open label study. Seven patients completed the initial 10 week study achieving doses of 50-70 mg/day without any significant change in their clinical status. Six patients continued for an additional 3-11 weeks with increases in dose to 65-100 mg/day. Two of the three most severely affected patients had mild worsening of parkinsonian symptoms. Buspirone is ineffective in the treatment of Parkinson's disease, but at anxiolytic doses (less than 40 mg/day) does not adversely affect parkinsonian disability.

The side effect profile of buspirone in comparison to active controls and placebo.

Animal studies and the original study comparing buspirone with diazepam and placebo indicated that sedative-hypnotic side effects and impairment in psychomotor function would be less with buspirone than with diazepam. This was borne out by the present double-blind study in which almost 700 patients received buspirone. Mean daily doses were buspirone, 20 mg; diazepam, 20 mg; and clorazepate, 24 mg. Sedation, lethargy, and depression were significantly less with buspirone than with diazepam or clorazepate and were comparable to placebo. There was no indication that other types of side effects would differ significantly from those seen with the benzodiazepines. Nervousness, headache, and dizziness were experienced more frequently with buspirone than with placebo.