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Neurontin (gabapentin)
(reviewed 8/2005)

Gabapentin (U.S. Neurontin) is a great example of how initial excitement about a medication can be misleading. 

There are multiple open trials (no placebo group) reporting very positive results.Erfurth, Letterman There are clearly many patients for whom Neurontin, at first, is a great thing:  it seems to act like an antidepressant and an antianxiety medication at the same time.  But after a while, for almost all patients I've seen, those benefits are lost.  After the first year of using the medication I found I had no patients who were still doing well on it alone.  Then the "controlled trials", with placebo groups, started to be appear.

The main multi-center study, sponsored by the manufacturer, showed Neurontin slightly less effective than placebo, and the results were not published.Sachs(a),Zarate  for quite a while.  This study finally did appear.Pande   A second randomized trial by The National Institute of Mental Health (small sample, but well-controlled) found no difference between gabapentin and placebo.Frye  Perhaps the most conclusive evidence it does not work well comes from the actions of the manufacturer itself, which has chosen not to pursue any more studies of gabapentin as a mood stabilizer.Zarate 

And yet, gabapentin clearly helps some people. The results can be dramatic.  One of my patients said "after 15 minutes following the first dose, my joy receptors turned back on".  But within about 6 months it was clear that Neurontin was causing the same rapid cycling that he had experienced on antidepressants.  Overall, this is my main concern about Neurontin. 

Think about it:  if some people respond very well, yet the overall data show it no better than placebo — some people must be getting worse! I think I’ve seen a lot of them.  I stopped using gabapentin, except with great caution, about 8-12 months after we first began using it. Dr. Sachs at Harvard has the same hesitation.Sachs(b)  In my view it should be considered an antidepressant option, to be used with great caution just like antidepressants in bipolar disorder. 

The director of the University of Massachusetts Bipolar Program states "I would not put it first-, second- or third-line on the decision tree", and "never as monotherapy"Zarate.