Second Generation Antidepressants: A Comparative Review

The authors review four “second generation” antidepressants (maprotiline, amoxapine, trazodone, and nomifensine) in terms of action on biogenic amines and receptors, antidepressive efficacy, and adverse effects. Doxepin is used as a comparative agent and is similar to the prototypical tricyclic agents in all the above categories. Maprotiline is a selective noradrenergic agent, but shares a similar adverse effect profile with doxepin and may be associated with a high frequency of seizures in overdose. Amoxapine is a mixed action antidepressant with significant neuroleptic activity in vivo. Its adverse effect profile is highlighted by symptoms related to its neuroleptic activity, and seizures and acute renal failure in overdose. Trazodone is a selective serotonergic agent with low anticholinergic activity, and minimal morbidity/mortality in overdose. Reports of priapism, leading to impotence in some men, however, is of concern. Nomifensine is a potent noradrenergic and dopaminergic agent with low anticholinergic activity, and minimum cardiotoxicity and low morbidity/mortality in overdose. Its most important adverse effects include overstimulation and infrequent, usually reversible, immunologic hypersensitivity reactions. Trazodone and nomifensine have favorable profiles for use in the elderly. Trazodone may be more favorable in the anxious/agitated patient due to its sedative effects, whereas nomifensine may be more beneficial in the retarded, apathetic patient.