A preliminary open study of the tolerability and effectiveness of nefazodone in major depressive disorder: comparing patients who recently discontinued an SSRI with those on no recent antidepressant treatment.

Anecdotal evidence suggests that the recent discontinuation of an SSRI may confound the tolerability of the initiation of nefazodone treatment. We sought to determine whether recent discontinuation of an SSRI interferes with effectiveness and/or tolerability of nefazodone. Twenty-six depressed subjects, 21-63 years old, were recruited at the Massachusetts General Hospital. Thirteen subjects (50%) had discontinued an SSRI within 1-4 weeks due to ineffectiveness and/or side effects. Thirteen subjects (50%) had not taken antidepressants for the previous 6 months. Subjects were administered open nefazodone 50 mg p.o. b.i.d., and doses were increased as tolerated to a maximum of 600 mg/day. Subjects were followed for 12 weeks and were assessed for response and side effects using HAM-D-6 and clinical interviews. Both groups improved significantly on nefazodone; however, there was no statistically significant difference in response (>or=50% decrease in HAM-D-6) rates between completers with prior SSRI treatment (80%) and completers without recent exposure to antidepressants (67%). Response rates based on intent-to-treat (ITT) analysis were 31% for both groups. Association between prior SSRI treatment and discontinuation of nefazodone due to side effects or non-response was not statistically significant. Our study suggests that the rate of negative outcomes with nefazodone is no different whether patients have recently failed an SSRI.