Protest Articles Submitted:

Submitted 10/16/05 to Clinical Practice and Epidemiology in Mental Health as a comment letter in response to: Combination quetiapine therapy in the long-term treatment of patients with bipolar I disorder
MC Hardoy , Alessandra Garofalo , Bernardo Carpiniello , JR Calabrese and MG Carta
Clinical Practice and Epidemiology in Mental Health 2005, 1:7     

I am very troubled by the publication and especially the claims of this very small, open trial. First, open trials have been repeatedly shown to be extremely susceptible to bias. That is why they are not part of evidence-based medicine. They strongly mislead physicians into thinking that something has been proven and, thus, alter clinical practice. That is exactly why manufacturers love to subsidize open trials, as in this case.

The authors statement that their study showed that "quetiapine combination therapy reduced the probability of manic/mixed and depressive relapses and improved symptoms in patients with bipolar I disorder" is claiming that this study proved something. It did not. An open trial can never prove cause-effect, especially such a small trial in such a subjectively measured condition and with no randomization to placebo and active comparators.

While I don't doubt that quetiapine may have the claimed benefits, this particular report proved absolutely nothing.

As to the authors claim that they have no competing interest, this study was supported by the manufacturer of quetiapine (Seroquel). I am also certain that these authors have received many benefits from various psychiatric pharmaceutical manufacturers over the past year including funding for other studies and that this publication is bound to make these and similar manufacturers more likely to give future funding to these authors. All of those benefits, and the support for this study by Astra-Zeneca are competing interests.

In my opinion, open trials should never be published. They have been responsible for the recent gabapentin and topiramate scandals in which tens of thousand of North American bipolar patients have been subjected to totally unproven and potentially harmful therapies with no informed consent, no IRB, and no scientific goal. At least 25% of American psychiatrists started prescribing these two drugs after being influenced by dozens of bogus open trials, most or all subsidized by the manufacturers. In the case of gabapentin, it resulted in a US$200,000,000 fine against the manufacturer, the largest fine in FDA history. Only since then have five out of five double-blind studies proven that topiramate is worthless for the treatment of bipolar manic or mixed states (1-2) and three out of three double-blind studies proven the same for gabapentin (3-5). However, the manufacturer has, to date, suppressed the publication of the unfavorable topiramate studies and the same may be true for some additional gabapentin studies.

Sincerely,

Thomas E. Radecki, M.D.

1. Ann Gen Psychiatry. 2005 Feb 16;4(1):5
2. Open-label adjunctive topiramate in the treatment of unstable bipolar disorder. McIntyre RS, et al. Can J Psychiatry. 2005 Jun;50(7):415-22.
3. Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. Pande AC, Crockatt JG, Janney CA, Werth JL, Tsaroucha G. Bipolar Disord 2000 Sep;2(3 Pt 2):249-55.
4. Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Obrocea GV, Dunn RM, Frye MA, Ketter TA, Luckenbaugh DA, Leverich GS, Speer AM, Osuch EA, Jajodia K, Post RM. Biol Psychiatry 2002 Feb 1;51(3):253-60.
5. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. Frye MA, et al. J Clin Psychopharmacol 2000 Dec;20(6):607-14.