Is selectivity for serotonin uptake associated with a reduced emergence of manic episodes in depressed patients?
To determine whether selectivity for serotonin reuptake plays a role in antidepressant-associated mania (AAM), we evaluated the frequency of treatment-emergent mania in patients with unipolar depression who received either citalopram, a highly selective serotonin uptake inhibitor, or the adrenergic tetracyclic antidepressants (TTCAs) maproriline and mianserin, or placebo. Data were collected from post-marketing reports of adverse events, three placebo-controlled trials and four double-blind comparative trials. Of the total 4,004 depressed patients treated with citalopram (2482 from postmarketing 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 patient (1/840, 0.12%). The citalopram-treated patients in whom AAM developed were significantly older than those in whom it did not (about 10 years, P < 0.001); gender distribution was similar. In conclusion, despite its limitations, our study apparently indicates that citalopram, a highly selective serotonin reuptake inhibitor, is associated with a significantly lower rate of treatment-emergent manic episodes than TTCAs, which have noradrenergic activity, but a similar rate to that reported for less selective SSRIs.
Barak
Y
Y
Abarbanel Mental Health Centre, Bat Yam, Israel.
Kimhi
R
R
Weizman
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000209:etiology* / Q000523:psychology; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use; D003866:Depressive Disorder / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008376:Maprotiline / Q000009:adverse effects / Q000627:therapeutic use; D008803:Mianserin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D008376:Maprotiline; D008803:Mianserin; D017367:Selective Serotonin Reuptake Inhibitors