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Antidepressant Withdrawal Can Last Months?
(written 9/2008) 

Summary:  When a patient with bipolar disorder is taking an antidepressant, and the decision is made to stop that medication, how slowly should it be tapered off? Although one expert has recommended taking as long as 4 months; and although I've found that rate to work much better than shorter tapers (e.g. 3 - 4 weeks or less, as I formerly recommended); there has been no study to help decide how fast or slow to go. 

The paper below may help, at least indirectly. It suggests that when antidepressants are tapered off, even slowly, the effects of that withdrawal persist for up to 4 months.  

If that was enough to interest you in this issue, read on. The evidence is indirect, I grant you.  The study here is Ristanovic and colleagues, 2008.


Here's the scenario.  These data come from a study of patients with narcolepsy.  In that illness, people can have sudden episodes of falling asleep, during the daytime.  They literally fall, sometimes, collapsing to the ground. Such episodes are called cataplexy.

Antidepressant medications can decrease the frequency of cataplexy in patients with narcolepsy. Thus when a new medication for cataplexy was being studied, it was necessary to taper patients off of any antidepressant they were already taking prior to starting the study medication. After the study was over, the authors recognized that something striking had happened even before the study medication was begun.  When antidepressants were stopped, it took weeks, many weeks, for the impact of that medication withdrawal to finally subside.

Since antidepressants are thought to prevent cataplexy, it makes sense that the frequency of episodes would increase when the antidepressant was stopped.  But as you can see in the graph below, the increase lasted a long time, suggesting that the physiologic changes associated with removing an antidepressant take months to stabilize, despite a 3-week tapering (which begins at the point labeled "Start"):

(The time scale represents 4 points in the study, not days, so the times shown are rough but accurate )

You may be asking "hey, wait a minute, they ended up back where they started. Doesn't that mean the antidepressant wasn't doing anything , before it was stopped?" The authors of this study raise that question too. But that's for the  narcolepsy researchers to figure out.  The point here is to recognize how long, physiologically, the effects of stopping an antidepressant persisted.

Bottom line: these data suggest that when an antidepressant is stopped, the brain response can take four months.  Whether these data apply in bipolar disorder is an open question.  But until now, I had never seen any data consistent with the idea that the process could take this long, even though I was recommending to patients that we should take four months to stop an antidepressant (based on one expert's recommendation, and my subsequent clinical experience suggesting that he was right).

 

Update 2012: I published this analysis, eventually: Phelps. And a colleague helped list 31 guidelines for more slowly stopping antidepressants