Wednesday, September 20, 2006

Modafinil for atypical depression

The Journal of Clinical Psychopharmacology has published the results of a controlled trial (sort of) of modafinil for atypical depression in adults. Modafinil is a relatively new agent (it is activating & increases alertness) indicated for narcolepsy but is being used here & there in the cancer population for fatigue as well as by some for opioid-induced fatigue/somnolence (somewhat akin to our use of methylphenidate). As far as I know this practice, while probably effective, doesn't have much of a literature base to support it. This study was a trial of modafinil for atypical depression (characterized by hypersomnolence, hyperphagia, anergia, etc.) in adults. The patients took open-label modafinil for 12 weeks, starting at 100mg QAM, and titrating up every few days in 100mg increments to a max dose of 400mg daily. Essentially there was a substantial and marked response in the patient's depressive symptoms after 12 weeks across the cohort. After 12 weeks responders (which was essentially the whole cohort) were randomized to continuation of modafinil or placebo and they were followed for another 12 weeks. After these 12 weeks, interestingly, there were no discernible differences between the modafinil and placebo groups--both had continued alleviation of their depressive symptoms. There were no major complications in the trial due to modafinil.

What to make of the 2nd 12 weeks? Either there was a major placebo response across the cohort to modafinil, which really didn't do much in and of itself; or modafinil can induce a lasting remission from atypical depression with just 12 weeks of therapy. I'm not sure of another good explanation to this. What seems to be needed is a true randomized placebo controlled trial using placebo from the outset, although for unclear reasons the authors recommend a long term randomized discontinuation trial which would seem to muddy the water too much. I've avoided modafinil in my fatigued/asthenic/sleepy patients who I thought were depressed (opting instead for methylphenidate) but this trial will probably change that a little: I'll give it a try in my depressed patients as well, even if it is "just" a placebo-effect. Leave comments if you've been using this with your patients for depression, opioid-induced sedation, or cancer-related fatigue--I'm curious about people's experiences with it.

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