Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance and core symptoms of depression

Background: SSRIs resolve depression slowly and may increase anxiety or ins omnia. Adding clonazepam to fluoxetine sped response, raising the question of mechanism of action: reducing symptoms co-existing with depression, supp ressing side-effects, and/or alleviating core depressive symptoms. Method: Adult outpatients randomly assigned to double-blind treatment with fluoxeti ne 20 mg + placebo or fluoxetine + clonazepam 0.5-1.0 mg were assessed by a HAM-D anxiety cluster, sleep disturbance cluster, and core symptoms cluste r. Results: No serious AEs were noted; no cotherapy patients: dropped for A Es. Cotherapy proved superior (HAM-D total, anxiety cluster, sleep disturba nce cluster ANOVA P < 0.001; core symptoms P < 0.011). Treatment-emergent a nxiety was reported for 25% of placebo patients and 7% of cotherapy patient s (P < 0.037); sleep disturbance for 10% of placebo patients and no cothera py patients: (P < 0.055). Sedation and dry mouth were more common for cothe rapy treatment (P > 0.20). Limitations: Extended treatment and refractory d epression were not addressed. Conclusions: Low-dose cotherapy of fluoxetine with clonazepam was safe and accelerated response over 21 days of treatmen t, decreasing anxiety and sleep disturbance as symptoms and partially suppr essed them as SSRI side-effects: it also modestly reduced core symptoms of low mood and loss of interest. (C) 2000 Elsevier Science B.V. All rights re served.