Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?
BACKGROUND
Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension.


METHODS
Fifty outpatient volunteers aged 18-65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months.


RESULTS
No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, df=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy.


CONCLUSIONS
Small sample size (N=50) limited power and rendered conclusions tentative.


CONCLUSIONS
Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated.
Smith
Ward T
WT
Summit Research Network, 1849 NW Kearney, Portland, OR 97209, USA. wsmith@summitnetwork.com
Londborg
Peter D
PD
Glaudin
Vincent
V
Painter
John R
JR
D000284:Administration, Oral; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy; D002998:Clonazepam / Q000008:administration & dosage / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D018757:GABA Modulators; D005473:Fluoxetine; D002998:Clonazepam