Evaluation of amoxapine

Abstract

The pharmacology, pharmacokinetics, clinical trials, side effects, and dosage of amoxapine are reviewed. Amoxapine is a tricyclic dibenzoxazepine antidepressant that is chemically similar to the antipsychotic agent loxapine. In animal tests, amoxapine and its metabolites block reuptake of the neurotransmitter norepinephrine, with little effect on serotonin. It is rapidly and virtually completely absorbed when administered orally; peak serum concentrations occur one to two hours after ingestion. Amoxapine is widely distributed throughout body tissues and is 90% bound to serum proteins. Aromatic hydroxylation in the liver produces two major metabolites, which are excreted in the urine primarily but also in the feces. Amoxapine's elimination half-life is eight hours; one of the metabolites has a long half-life (30 hours). In clinical trials, amoxapine has been compared with amitriptyline and imipramine in several types of depressed patients. In some studies, amoxapine's therapeutic effects were measurable earlier (at one or two weeks after initiation of therapy) than those of the amitriptyline or imipramine, but generally only a portion of the depression-rating scales yielded statistically significant differences. Side effects noted during amoxapine therapy include hypotension (42%), drowsiness (14%), xerostomia (14%), constipation (12%), blurred vision (7%), fatigue (5%), and vertigo (5%). Amoxapine is approved by FDA for use in patients with neurotic or reactive depressive disorders, endogenous or psychotic depression, and depression accompanied by anxiety or agitation. The usual adult dosage is 200-300 mg daily, either in divided doses or a single bedtime dose. Amoxapine is a safe and effective antidepressant with no striking advantages over other available agents.