Diazepam clinical trials anxiety

Ondansetron. The S-HTj antagonist ondansetron has been reported to be effective in the treatment of generalized anxiety disorder, with efficacy comparable to that of diazepam [Lader 1991). Sedation and rebound anxiety during withdrawal from ondansetron were not observed [Lader 1991). Ondansetron has been considered for phase 111 clinical trials for the treatment of social phobia and panic disorder. 

BZDs may exacerbate depression and possibly increase suicide risk. Case reports and clinical trials also indicate that BZD treatment of generalized anxiety and panic may result in emergence of depression (215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225 and 226). In some of these reports, depression is ill-defined, but in others, it met DSM-III criteria for a major depressive disorder, requiring treatment with an antidepressant ( 225, 226). Depression has been reported with a variety of BZDs (alprazolam, bromazepam, clonazepam, diazepam, lorazepam), but there is no evidence that one is more likely than another to cause or aggravate depressive illness. 

Clinical trials of buspirone have shown the drug to be slower in onset of action compared with diazepam, but it produces significantly less sedation and fewer detrimental effects on psychomotor function than the benzodiazepines. The main advantage of buspirone would therefore appear to be in its lack of dependence, amnestic and sedative effects. However, its slower onset of action and its lower efficacy in alleviating the somatic symptoms of anxiety make it unlikely that it will replace the therapeutically effective and proven benzodiazepines, despite the greater frequency of their side effects. Whether ipsapirone and gepirone, which are still in clinical development, will be therapeutically superior to buspirone can only be assessed after they become more widely available for clinical use. 

Although the BZs show a robust anxiolytic effect, many of the clinical trials were conducted before the currently used divisions between specific anxiety disorders became available (4). As a result, knowledge of their efficacy in discrete anxiety disorders is incomplete. In clinical practice (48) BZs are widely used for GAD and as prophylactics in situational anxiety, with diazepam (l)historically being the most popular choice. Others in common use are chlordiazepoxide (2), clorazepate (3), lorazepam (4), alprazolam (5), oxazepam (6), bromazepam (7), and clonazepam (8) Response rates are high and the onset of therapeutic effect is immediate. This is an important contrast to the MAOIs, TCAs, and SSRIs, where an anxiolytic effect is not seen for several weeks. Although not specifically approved for this disorder. BZs are also effective in social phobia, with clonazepam (49) showing a superior response rate to that of alprazolam (50). Alprazolam and clonazepam are the only BZs approved for the treatment of panic disor-... 

Benzodiazepine dosage reqnirements vary widely among patients and mnst be individnahzed. Therapy shonld be initiated using low doses (e.g., diazepam 2 mg three times daily, alprazolam 0.25 mg three times a day or eqnivalent doses of other benzodiazepines) and titrated npward to reheve anxiety symptoms and avoid adverse events. After an initial treatment response is achieved, agents with long elimination half-hves can be dosed at bedtime. Dosage adjustments shonld be made weekly. Three to four weeks of a daily dose at the maximum dose constitutes an adeqnate clinical trial. ... 

---