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Ask the Mental Health Expert Archives 2001-2004

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Neurontin's Effectiveness

Q. I heard on National Public Radio, on their "All Things Considered" program about Neurontin and that there is no substantial documentation of effectiveness in treating bipolar disorder. According to the report, sugar pills are more effective than the drug. Because the drug has little potential for overdosing, the company recommended increasing the dosage until effectiveness. My son was on this medication and it wasn't working so the psychiatrist kept increasing it. Eight months later my 16-year-old son committed suicide.

While researching I found that researchers found Neurontin had little efficacy for bipolar disorder as far back as 1999. Why then, do doctors continue to repeatedly prescribe and increase a dose of a medicine that was known not to be indicated?

Until today, I believed I had done everything humanly possible to try and help my son and believe me I am not naive to the mental health/medical world. But now I am left feeling that I really have let him down. For 6 months they continued to up his med, hoping for some alleviation. What is your opinion on this subject?

A. My heart goes out to you on the loss of your son. It is hard to appreciate the pain of such a loss unless one has been through it. But, I am quite sure that your son's suicide was infinitely more complicated than the use of a single medication, such as gabapentin [Neurontin]. Nor can I imagine that any parent could have anticipated the issues discussed on NPR, regarding the research behind this agent-even most mental health professionals seem to be behind the learning curve when it comes to this agent.

First of all, keep in mind that bipolar disorder itself is highly associated with suicide--as many as 1 in 5 patients with bipolar disorder eventually go on to take their own lives, when the naturalistic data are examined. (This means that all actual treatments are examined, as opposed to use of specific agents under controlled conditions). There is evidence that some mood stabilizers, such as lithium and possibly valproate, do reduce the risk of suicide, but do not eliminate the risk by any means.

Gabapentin became popular with clinicians treating bipolar disorder because it appeared to be helpful and was usually very well-tolerated. The key word here is appeared. Most of the early experience with this agent was uncontrolled--that is, based on clinical observations that did not include use of a placebo (sugar pill) for comparison. These so-called open studies from the mid-to-late 1990s seemed to be favorable. But most cases involved the use of Neurontin as an adjunctive agent--that is, as an add-on to better-validated mood stabilizers, such as lithium or valproate.

In the last couple of years, there have been several controlled studies of gabapentin monotherapy (the agent used by itself) that have failed to confirm the earlier impressions of benefit (e.g., Frye MA, Ketter TA, Kimbrell TA et al: A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol 2000; 20:607-14; Pande AC, Crockat JG, Janney CA et al: Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Bipolar Disord 2000; 2:249-55).

This does not necessarily invalidate the earlier uncontrolled reports. Even though we say that controlled studies are the gold standard of research, there are patients whose improvement on a drug is submerged by the statistical effects of the group as a whole. Thus, there may still be individuals with bipolar disorder who do benefit from Neurontin. Even today, many experts in bipolar disorder consider Neurontin useful as an adjunctive agent in this condition. This does not mean, of course, that your son got the best possible professional care-but neither does the use of Neurontin by his clinicians necessarily point to sub-optimal care.

In any case, there is surely no reason to feel that somehow, you let your son down, solely on the basis of the Neurontin issue. As Shakespeare once said, suicide is "...the undiscovered country"--we still know little of its mysteries, even though we know it is highly associated with mood disorders. I am not trying to make excuses for anybody--but I am suggesting that despite the best of efforts, such tragedies sometimes occur. If you find that you are unable to stop blaming yourself for your son's death, I would urge you to get some counseling to help you deal with this.

On the other hand, if you truly believe that your son did not get the professional help he needed, you may want to pursue some further inquiries into his treatment and even consider legal action. I say this with some trepidation, however, since that path may simply re-activate the entire trauma for you. Here, too, getting some professional counseling might be helpful in sorting out your options. If you have not already joined, you may want to contact the National Depressive and Manic Depressive Association (1-800-826-3632), since they can often provide both information and emotional support. I hope that whatever course you take, you find peace for yourself.

August 2002

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