Efficacy of Modafinil for Treatment of Neurocognitive Impairment in Bipolar Disorder


An expert discusses the role of cognition in bipolar disorder and the potential of modafinil as a treatment for it at the 2024 ASCP Annual Meeting.




“Cognition is a very key component of bipolar disorder. It drives the disease, is an incredibly important part of functioning in the world, and has not really been considered properly as a treatment target.”

Katherine E. Burdick, PhD, spoke on a panel of experts who discussed the potential of modafinil/armodafinil as a treatment for bipolar disorder targeting cognition, depression, and sleep circadian rhythm at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting. Burdick is Jonathan F. Borus, MD, Distinguished Chair in Psychiatry and vice chair for research in the Department of Psychiatry at Brigham and Women’s Hospital, and a professor at Harvard Medical School.

In her individual presentation, titled “A proof-of-concept study of modafinil for neurocognitive impairment in bipolar disorder,”1 Burdick discussed a recent pilot study that investigated the effects of modafinil—which is currently approved by the US Food & Drug Administration for managing excessive sleepiness in conditions like shift work disorder and narcolepsy2—on neurocognitive functioning, daytime sleepiness, and sleep quality in patients with bipolar disorder who are in a state of relative remission.1

Despite advancements in bipolar disorder treatment, according to Burdick, many patients with bipolar disorder—which consistently ranks among the top 10 leading causes of disease in the world—continue to struggle with neurocognitive dysfunction, decreased daytime activity, and sleep disturbances even during periods of remission. The study Burdick discussed aimed to explore a potential new avenue for improving the quality of life for these patients.1

Burdick shared that the 8-week, randomized, placebo-controlled pilot study included 12 individuals who had been diagnosed with affectively stable bipolar disorder. Participants were randomly assigned to receive either modafinil (at doses ranging from 100 to 200 mg/day) or a placebo, in addition to their regular mood stabilizer medication. The study involved weekly in-person visits to monitor sleep quality, daytime sleepiness, adverse events, and mood symptoms. Neurocognitive functioning was assessed at baseline, week 4, and week 8.1

The preliminary results indicated a marginally significant improvement in 2 cognitive domains—speed of processing and verbal learning—in the modafinil group compared with the placebo group. According to Burdick, this suggests a potential cognitive benefit of modafinil for patients with bipolar disorder. There was also a marginally significant reduction in daytime sleepiness in those taking modafinil compared with those taking the placebo, indicating that modafinil may help alleviate 1 of the persistent issues faced by patients with bipolar disorder.1

However, the study also found that sleep quality improved more significantly in the placebo group than in the modafinil group. According to Burdick, this counterintuitive result suggests that, although modafinil may help with cognitive function and daytime alertness, it might negatively affect sleep quality.1

Modafinil was generally well-tolerated among participants, with no serious adverse events reported. However, some patients in the modafinil group experienced adverse events such as heart palpitations, itching, fatigue, and decreased energy. Due to adverse events, 2 patients discontinued modafinil, and 1withdrew from the study. One patient in the placebo group also discontinued and withdrew from the study.1

“Results suggest that modafinil is a relatively safe medication for affectively stable patients with bipolar disorder when given with adjunctive mood stabilizers,” Burdick concluded. “Although very preliminary, our results are suggestive of cognitive benefit and improved daytime sleepiness. Given the finding of worse sleep quality in those patients prescribed modafinil, methodological changes to drug administration should be considered in future work. A fully powered clinical trial is warranted with specific attention to the characteristics of patients who are most likely to benefit from treatment with modafinil and other methodological lessons learned from this pilot.”

Burdick was joined on this panel by Mark A. Frye, MD, and Ellen Frank, PhD. Frye is a consultant in the Department of Psychiatry & Psychology and a professor of psychiatry at Mayo Clinic College of Medicine. Frank is a distinguished professor emeritus in the Department of Psychiatry at the University of Pittsburgh School of Medicine and chief scientific officer at Health Rhythms Inc.

In the overall panel presentation, Burdick, Frye, and Frank reviewed the methodological limitations associated with developing modafinil/armodafinil for bipolar depression and discussed cognitive impairment and circadian rhythm issues in bipolar disorder as targets for modafinil/armodafinil.

Follow the Psychiatric Times® coverage of the 2024 ASCP Annual Meeting, and stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders, at psychiatrictimes.com.

Note: This article was prepared with the assistance of ChatGPT.


1. Frye M, Burdick K, Frank E. ~Revisiting modafinial / armodafinil in bipolar disorder targeting cognition, depression, and sleep circadian rhythm. Panel presentation. 2024 American Society of Clinical Psychopharmacology Annual Meeting. May 28, 2024.

2. Monderer R, Thorpy MJ. Modafinil/armodafinil in the treatment of excessive daytime sleepiness. In: Thorpy MJ, Billiard M, Eds. Sleepiness: Causes, Consequences and Treatment. Cambridge University Press; 2011.

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