Fish oils and bipolar disorder: a promising but untested treatment.

Calabrese, J.R., Rapport, D.J,, Shelton, M.D. (1999) Arch Gen Psychiatry 56(5) 413-4; discussion 415-6.

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Abstract:

Commentary - no abstract available. The following is only an abridged version of this article. Please see the full test for the details provided concerning study design limitations.

In this issue of the Archives, Stoll and colleagues report innovative preliminary data on the putative mood-stabilizing properties of a fish oil containing ω3 fatty acids in the treatment of bipolar disorder (types I and II). Acting on the assumption that overactive cell-signaling pathways may be involved in the pathophysiological characteristics of bipolar disorder, and the finding that ω3 fatty acids are associated with a general dampening of signal transduction pathways associated with phosphatidylinositol, arachidonic acid, and other systems, Stoll et al performed a controlled study to explore the mood-stabilizing effects of high-dose ω3 fatty acids.

In this study, subjects were randomly assigned to parallel groups after stratifying for sex, recent lithium use, and a history of rapid cycling. The primary outcome measure was the duration of time to exit the blinded phase of the study for treatment of an emerging mood episode; the decision to end treatment was at the discretion of the investigators. The secondary outcome measures included 4 symptom-severity scales that were analyzed using an intent-to-treat analysis with the last observations carried forward.

In the review of this study, we noted that it was neither a typical acute nor a maintenance study.
The use of survival analyses, despite the short study duration, could be considered somewhat unusual, particularly because the index episodes were not standardized.
The secondary analyses were further complicated by the a priori requirement that subjects remain in the study for longer than 29 days to be included in the intent-to-treat analysis

Despite these substantial limitations, this study represents a landmark attempt in drug development for bipolar disorder because a naturally occurring dietary component was evaluated for its mood-stabilizing efficacy. As evidence of the importance of this area of research, the National Institutes of Health conducted a workshop on ω3 essential fatty acids and psychiatric disorders in 1998.

In an attempt to replicate and extend these preliminary findings, we recommend a series of double-blind, placebo-controlled studies evaluating the efficacy and dose-response relationships of ω3 fatty acids in the various phases of the illness, including both acute and maintenance designs in bipolar disorder (types I and II).

Given the spectrum of efficacy reported in the secondary analyses of the data of Stoll et al, we recommend an initial study in patients currently experiencing depressive episodes associated with type I bipolar disorder. After guaranteeing minimum severity at the time of study entry by requiring a minimum score on either the Montgomery Asberg Depression Rating Scale or the 17-item Hamilton Rating Scale for Depression, one could then use random assignment to parallel groups comparing 2 doses (10 g/d and 5 g/d) of ω3 fatty acids to placebo during an 8- to 12-week study.

FAB RESEARCH COMMENT:

While acknowledging the landmark nature of the study by Stoll and colleagues published in the same issue of Archives (Stoll et al, Arch Gen Psychiat 1999) this commentary helpfully points out some possible limitations of the study design relevant to the interpretation of the study findings, and highlights the need for further studies.

See also

the reply from Stoll and colleagues (Stoll & Marangell, Arch Gen Psychiat 1999)

the subsequent Cochrane Review on this subject: Montgomery P, Richardson AJ (2008) Cochrane Database Syst Rev. 2008 Apr 16;(2) CD005169.

For more information on this area since this landmark research was published, see the following list of research studies, which is regularly updated:

Omega-3 and Bipolar Disorder - Research

< Byrne M K et al 2024 - Dietary Intakes of Long-Chain Polyunsaturated Fatty Acids and Impulsivity: Comparing Non-Restricted, Vegetarian, and Vegan Diets

Calarge et al 2010 - Serum ferritin and amphetamine response in youth with ADHD >

UK Nutrient Gaps and Impacts on Early Development with Dr Emma Derbyshire and TC Callis - BOOK HERE

Fish oils and bipolar disorder: a promising but untested treatment.

Abstract:

FAB RESEARCH COMMENT:

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