Is selectivity for serotonin uptake associated with a reduced emergence ofmanic episodes in depressed patients?

To determine whether selectivity for serotonin reuptake plays a role in ant idepressant-associated mania (AAM), we evaluated the frequency of treatment -emergent mania in patients with unipolar depression who received either ci talopram, a highly selective serotonin uptake inhibitor, or the adrenergic tetracyclic antidepressants (TTCAs) maprotiline and mianserin, or placebo. Data were collected from post-marketing reports of adverse events, three pl acebo-controlled trials and four double-blind comparative trials. Of the to tal 4004 depressed patients treated with citalopram (2482 from postmarketin g data, 840 from placebo-controlled studies and 682 from TTCAs comparative studies), 25 (0.62%) had manic episodes. The rate of AAM in the comparative trials was significantly lower in the citalopram-treated patients (1/682, 0.15%) than in the TTCA-treated patients (5/389, 1.29%) (P = 0.03). In the placebo-controlled studies, no manic episodes were reported in the patients given placebo, but one manic episode occurred in a citalopram-treated pati ent (1/840, 0.12%). The citalopram-treated patients in whom AAM developed w ere significantly older than those in whom it did not (about 10 years, P < 0.001); gender distribution was similar. In conclusion, despite its limitat ions, our study apparently indicates that citalopram, a highly selective se rotonin reuptake inhibitor, is associated with a significantly lower rate o f treatment-emergent manic episodes than TTCAs, which have noradrenergic ac tivity, but a similar rate to that reported for less selective SSRIs. (C) 2 000 Lippincott Williams & Wilkins.