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 insomnia. Adding clonazepam to fluoxetine sped response, raising the question of mechanism of action: reducing symptoms co-existing with depression, suppressing side-effects, and/or alleviating core depressive symptoms. Method: Adult outpatients randomly assigned to double-blind treatment with fluoxetine 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 cluster. Results: No serious AEs were noted; no cotherapy patients dropped for AEs. Cotherapy proved superior (HAM-D total, anxiety cluster, sleep disturbance cluster ANOVA P<0.001; core symptoms P<0.011). Treatment-emergent anxiety was reported for 25% of placebo patients and 7% of cotherapy patients (P<0.037); sleep disturbance for 10% of placebo patients and no cotherapy patients (P<0.055). Sedation and dry mouth were more common for cotherapy treatment (P>0.20). Limitations: Extended treatment and refractory depression were not addressed. Conclusions: Low-dose cotherapy of fluoxetine with clonazepam was safe and accelerated response over 21 days of treatment, decreasing anxiety and sleep disturbance as symptoms and partially suppressed them as SSRI side-effects; it also modestly reduced core symptoms of low mood and loss of interest.