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Dr. Fenton and Colleagues Reply

To the Editor: We share Dr. Horrobin’s disappointment that 3 g/day of ethyl EPA added to a current antipsychotic medication regimen was no more effective than placebo in reducing residual symptoms and cognitive deficits in patients with schizophrenia. In agreement with Dr. Horrobin, we indicate that potential explanations for our failure to find a therapeutic effect might include 1) the relative illness duration and severity of our study group, 2) inadequate or excessive doses of ethyl EPA, 3) an inadequate duration of treatment, or 4) ineffectiveness of the putative therapeutic agent. On the other hand, we do not concur that "it is unlikely that any standard drug would show benefit in a trial with this add-on design." Add-on designs such as this have demonstrated the benefit of many augmentation strategies, including lithium augmentation of antidepressants (1), D-cycloserine augmentation of conventional antipsychotic agents for negative symptoms in schizophrenia (2), and pindolol augmentation for patients with treatment-resistant panic disorder (3). Contrary to Dr. Horrobin’s contention, if the hypothesis under consideration is that supplemental therapy is beneficial to patients with residual symptoms and deficits despite adequate treatment with standard approaches, a double-blind placebo-controlled add-on study would appear to be the only appropriate experimental design to rigorously assess the hypothesis. Finally, in our view, our failure to find any correlation between changes in the arachidonic acid/EPA ratio and improvement in clinical dependent variables renders unlikely the hypothesis that a diet change in the placebo-treated group explains improvement in both groups. Given that the bulk of the placebo effect for both groups was seen in the first 2 weeks of treatment, however, we recommend that future studies consider using a single-blind placebo lead-in period. Further research will be needed to clarify the potential use of ethyl EPA in schizophrenia and other neuropsychiatric conditions.

References

1. Dording CM: Antidepressant augmentation and combinations. Psychiatr Clin North Am 2000; 23:743-755[CrossRef][Medline]
2. Goff DC, Tsai G, Levitt J, Amico E, Manoach D, Schoenfeld DA, Hayden DL, McCarley R, Coyle JT: A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 1999; 56:21-27[Abstract/Free Full Text]
3. Hirschmann S, Dannon PN, Iancu I, Dolberg OT, Zohar J, Grunhaus L: Pindolol augmentation in patients with treatment-resistant panic disorder: a double-blind, placebo-controlled trial. J Clin Psychopharmacol 2000; 20:556-559[CrossRef][Medline]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by FENTON, W. S. Articles by KNABLE, M. B. Search for Related Content Articles by FENTON, W. S. Articles by KNABLE, M. B. Atypical Neuroleptics Conventional Neuroleptics Schizophrenia Spectrum Disorders Other Neuroleptics

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