Marine omega-3 fatty acids may be a promising add-on therapy for improving symptoms of borderline personality disorder (BPD), new research suggests.
A meta-analysis of four randomized controlled trials showed that adjunctive omega-3 fatty polyunsaturated fatty acids (PUFAs) significantly reduced overall BPD symptom severity, particularly affect dysregulation and impulsive behavior.
“Given the mechanisms of action and beneficial side effect profile, this [analysis] suggests that omega-3 fatty acids could be considered as add-on treatment” for patients with BPD, senior author Roel J. T. Mocking MD, PhD, resident in psychiatry and postdoctoral researcher at Academisch Medisch Centrum, Amsterdam, the Netherlands, told Medscape Medical News.
The findings were published online recently in the Journal of Clinical Psychiatry.
“There are several effective treatments, but not all patients respond sufficiently,” which points to an urgent need for additional treatment options, Mocking said.
He noted that although “several prior studies showed promising effects of omega-3 fatty acids” for patients with BPD, those studies were relatively small, which precluded more definitive overall conclusions.
The current investigators wanted to combine results of the earlier studies to provide a combined estimate of overall effectiveness of the use of omega-3 fatty acids for patients with BP, with the intention of “guiding clinicians and individuals suffering from borderline personality disorder to decide on whether they should add omega-3 fatty acids to their treatment.”
The analyzed four studies that had a total of 137 patients. Three of the studies included patients diagnosed with BPD; one included individuals with recurrent self-harm, most of whom were also diagnosed with BPD.
Omega-3 fatty acids were used as monotherapy in one study. In the other studies, they were used as add-on therapy to other agents, such as antidepressants, benzodiazepines, and/or valproic acid. None of the studies included patients who were taking antipsychotics.
The type of omega-3 PUFAs were derived from marine rather than plant sources.
Three studies compared omega-3 fatty acids to placebo. One study compared valproic acid monotherapy to valproic acid plus omega-3 fatty acids and did not include a placebo group.
Significant Decreasing Effect
Random-effects meta-analyses showed an “overall significant decreasing effect” of omega-3 fatty acids on overall BPD symptom severity (standardized difference in means [SDM], .54; 95% CI, 0.91 – 0.17; P = .004) in the omega-3 group compared with the control group, with a medium effect size.
The investigators add that there was “no relevant heterogeneity” (P = .45).
The effects of omega-3 fatty acid supplementation on specific symptoms domains are listed in the following table.
|Symptom domain||Studies||SDM (95% CI)||P value||Evidence quality|
|Affective dysregulation||4||.74 (1.21 – .27)||.002*||Moderate|
|Impulsive behavioral dyscontrol||3||.45 (.84 – .059)||.02*||Moderate|
|Cognitive perceptual symptoms||2||.30 (.96 – .36)||.38||Low|
|Global functioning||2||.70 (1.80 – .40)||.21||Very low|
Although heterogeneity was “more pronounced” in the affective dysregulation symptom domain, it did not reach statistical significance, the researchers note.
The impulsive behavioral dyscontrol and cognitive perceptual symptom domains had “no relevant heterogeneity.” On the other hand, there was “substantial heterogeneity” in the global functioning symptom group.
Omega-3 fatty acids “have multiple bioactive roles in the brain. For example, they form essential components of the membrane of brain cells and thereby influence the structure and functioning of the brain. They also have an effect on inflammation levels in the brain,” Mocking said.
“Because we cannot synthesize these omega-3 fatty acids ourselves, we are dependent on our diet. The main dietary source of omega-3 fatty acids is fatty fish. However, since the industrial revolution, we eat less and less fatty fish, risking deficiency of omega-3 fatty acids causing brain dysfunction,” he added.
Mocking noted that the mechanisms of action of omega-3 fatty acids differ from those of other treatments for BPD, such as psychotherapy, antidepressants, or antipsychotics.
This “suggests that they could be combined to increase overall effectiveness,” he said.
Commenting on the study for Medscape Medical News, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Canada, and head of the Mood Disorders Psychopharmacology Unit, said that the benefit of omega-3 “on impulsivity and mood symptoms is especially important, as these are some of the most debilitating aspects of BPD and lead to service utilization, such as ER, primary care, and specialty care.”
In addition, “impulsivity often presages suicidality,” he noted.
McIntyre, who is also chair and executive director of the Brain and Cognition Discovery Foundation in Toronto and was not involved with the study, called the effect size “quite reasonable.”
“The mechanistic story is very strong around anti-inflammatory effect, which particularly implied mood and cognition. In other words, inflammation is highly associated with mood and cognitive difficulties,” he said.
However, McIntyre also pointed to several significant challenges, including “quality assurance on the purchase of the product of fish oil, as it is not sufficiently regulated.” It is also unclear which individuals are more likely to benefit from it.
For example, major depressive disorder data have shown that “fish oils are not as effective as we hoped but are especially effective in people with baseline elevation of inflammatory markers,” McIntyre said.
“In other words, is there a way to identify a biomarkers/biosignature or phenomenology that’s more likely to identify a subgroup of people with BPD who might benefit benefitting from omega-3?” he asked.
Mocking and the other investigators report no relevant financial relationships. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and Abbvie. McIntyre is also CEO of AltMed.
J Clin Psychiatry. Published online May 4, 2021. Abstract
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