In a major review of amoxapine and its pharmacology it was concluded that it is similar in efficacy and potency to standard tricyclic compounds, with a sedative action intermediate between amitriptyline and imipramine (1).
As previously noted (SEDA-4, 21) (SEDA-5,17), amoxapine has a tricyclic nucleus with a modified piperazine side chain and is closely related to the neuroleptic drug loxapine. In animals, amoxapine has no antiserotonergic properties and less anticholinergic activity than prototype drugs. Peak plasma concentrations are achieved in less than 2 hours, and the half-lives of the parent drug and its two active metabolites are 8, 6, and 30 hours respectively.
Overall, amoxapine appears to have some advantage over other tricyclic antidepressants: possible earlier onset of action and relative freedom from serious cardiotoxic effects. Its major drawbacks are the potential for neuroleptic adverse effects, a high incidence of seizures, deaths in overdose (2), and the possibility of long-term neurological damage.
Amoxapine is less potent than other tricyclic antide-pressants, with a therapeutic dosage range of 75600 mg/day (usually 200-400 mg/day). Clinical effects have not been consistently correlated with plasma concentrations, but amoxapine has similar efficacy to other tricyclic antidepressants in heterogeneous populations of depressed patients. Controlled comparisons have shown that its clinical profile is very similar to that of imipramine (3) and that it is somewhat less sedative than amitriptyline (4-6). In two of these studies (4,6) the results confirmed the suggestion of a somewhat earlier onset of action.
Amoxapine appears to have the same common adverse effects as other tricyclic compounds, including those attributable to anticholinergic activity. Its structural similarity to the classic neuroleptic drugs appears to confer an additional hazard of adverse effects usually found in that category of drugs, such as galactorrhea and extrapyramidal disorders (SEDA-9, 20). In a study of its potential neuroleptic properties (7), using a radioreceptor assay in vivo and using plasma drawn from patients taking neuroleptic drugs or antidepressants, amoxapine and its metabolite, 7-hydroxyamoxapine, had potent neuroleptic activity. In patients taking amoxapine, there was neuroleptic activity comparable to that in patients taking loxapine, while none of the other tricyclic antidepressants (amitriptyline, nor-triptyline, imipramine, and desipramine) had this property. Further reports of adverse effects attributable to its neuroleptic profile continue to appear, including tardive dyskinesia (8,9), acute torticollis (10), and malignant neu-roleptic syndrome (SEDA-16, 9) (SEDA-17, 18) (11).
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