A large-scale, living review has distilled the best available evidence on the efficacy and side effects of bipolar disorder (BD) treatments in a free online tool designed to help clinicians and patients make more informed treatment decisions in real time.

The Evidence Based Interventions for Bipolar Disorder (EBI-BD) platform is based on the results of an umbrella review evaluating the certainty of evidence for treatment strategies across age groups and mood phases in BD.

“While many trials and meta-analyses of these trials are available, what was lacking was a comprehensive evidence synthesis of all these meta-analyses across all types of interventions, outcomes, and age groups, as well as a user-friendly platform that reports all this evidence synthesis in a single place, making it easy for clinicians and patients to consult,” review author Samuele Cortese, MD, professor of child and adolescent psychiatry, University of Southampton, Southampton, England, told Medscape Medical News.

The review was published online on August 11 in The BMJ.

Ranked, Real-Time Evidence

The review included 77 network or pairwise meta-analyses covering 116 unique treatments, 133 outcomes, and 2510 meta-analytic comparisons. The interventions spanned medications, brain stimulation, nutraceuticals, psychosocial therapies, and treatments based on circadian rhythms. 

Cortese and an international expert panel graded the certainty of the evidence, finding 236 comparisons supported by high-certainty evidence and 827 by moderate-certainty evidence, with the remainder rated low or very low. Interventions supported by stronger evidence varied across phases of BD and by age.

For bipolar depression, multiple medications were supported in adults, including cariprazine, lurasidone, quetiapine, olanzapine and lamotrigine; evidence in children and adolescents was more limited, with evidence supporting lurasidone and olanzapine plus fluoxetine.

For mania, a broader range of treatments was effective in adults, including lithium, several antipsychotics and mood-stabilizing drugs. Five antipsychotics — aripiprazole, asenapine, olanzapine, quetiapine and risperidone — were supported in children and adolescents.

For maintenance, effective options across outcomes in adults included aripiprazole (including its long-acting injectable formulation), asenapine, divalproex or valproate, lithium, olanzapine, quetiapine and risperidone in long-acting injectable formulations, and group psychoeducation (augmentation).

Interventions effective across phases in adults included aripiprazole, asenapine, cariprazine, divalproex or valproate, lamotrigine, lithium, olanzapine, paliperidone, quetiapine and risperidone, as well as cognitive behavioral therapy as an adjunct treatment. Aripiprazole and risperidone were also effective in long-acting injectable formulations, and aripiprazole, olanzapine, quetiapine and risperidone showed efficacy as augmentation treatments.

Free Downloadable Dataset

The interactive EBI-BD platform allows users to filter the evidence by intervention, outcome and population, view ratings of study quality and certainty, and see graphic summaries of specific treatment comparisons. The site also offers plain-language summaries and makes the underlying dataset freely downloadable.

A central feature is a preference-based tool intended to help patients and clinicians weigh treatment benefits against side effects. Users can choose which adverse effects matter most to them and assign different levels of importance to each. An algorithm then uses those preferences to generate individualized rankings of drug treatments.

The authors plan to update the “living” review at least every 2 years, with additional updates if major new evidence emerges in the meantime.

“Research on bipolar disorder treatment moves so quickly that it’s nearly impossible to keep up. Now people with bipolar disorder and their clinicians can see all the latest evidence in one place to inform treatment decisions,” review author Marco Solmi, MD, PhD, psychiatrist at The Ottawa Hospital and professor and director of research for the University of Ottawa Department of Mental Health, Ottawa, Ontario, Canada, said in the statement. 

Useful but Not Prescriptive

An independent expert welcomed the effort to make the evidence more accessible, while offering a more nuanced view of how the platform should be used.

Holly A. Swartz, MD, professor of psychiatry at the University of Pittsburgh School of Medicine, Pittsburgh, and president of the International Society for Bipolar Disorders, noted that the web platform was created by a “very distinguished group” of researchers with a track record of doing this in other disease states.

“They’ve been very methodologically careful and the data supporting the website are quite sound,” she said.

Swartz welcomed its open-access model and the effort to present treatment benefits alongside side effects, which she said offers “a nice balanced perspective that can be very useful.”

She also praised the platform’s patient-centered approach and its plan to function as a living database, noting that traditional guidelines are typically out of date once they are published.

“It’s not going to tell doctors what to prescribe, but I think it’s a good ancillary source of information,” Swartz said.

Funding for this research was provided by the Canadian Institutes of Health Research, Agence Nationale de la Recherche (France), the France 2030 program, and the National Institute for Health and Care Research (UK). Disclosures for the authors are available with the original study publication. Swartz serves as editor-in-chief of the American Journal of Psychotherapy.