Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole, by LD Crosby, S Kalanidhi, A Bonilla, A Subramanian, JS Ballon & H Bonilla in Journal of Translational Medicine vol 19, Article number: 50 (2021)


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating illness of unknown etiology. An ME/CFS diagnosis is based solely on symptoms with case definitions made by expert consensus, including the Fukuda (1994), Canadian Consensus Criteria (CCC, 2003), International Consensus Criteria (ICC, 2011), and the Institute of Medicine (IOM, 2015) case criteria. According to the most recent IOM case definition, the core symptoms of ME/CFS include debilitating fatigue, unrefreshing sleep, post-exertional malaise, and either cognitive dysfunction or orthostatic intolerance [1].

Although the cause of the illness is unknown, a growing body of evidence suggests that ME/CFS involves inflammation of the brain. Up to 85% of patients with ME/CFS report symptoms of cognitive impairment also referred to as “brain fog,” which includes difficulty with memory, attention, and information processing. Additional evidence includes changes in inflammatory cytokines in both plasma and cerebrospinal fluid correlated with the severity of symptoms [2]. Other studies using positron emission tomography (PET) show evidence of activated microglia or astrocytes in various regions of the brain in patients with ME/CFS [3].

Dopamine D2 receptor agonists have been shown to mediate neuroinflammation, microglial activation, and cell death in animal models and humans [4,5,6]. This suggests that dopamine-modulating drugs like aripiprazole may lead to clinical improvement in fatigue and cognitive symptoms in ME/CFS. Given the lack of approved drugs for treating this condition, we were interested in exploring the potential benefit of low doses of aripiprazole in our Stanford University ME/CFS clinical practice.

In summary, the number of positive responders in a group of 101 patients taking aripiprazole was significantly greater than the number of patients who did not respond or had negative experiences. Also, the magnitude of perceived improvement was significant. Some patients failed to observe any benefit, and a small subset of patients experienced side effects that required the medication to be discontinued. Overall, these results suggest that aripiprazole may effectively reduce symptoms of ME/CFS and warrants further investigation in a randomized clinical trial. Exploring the mechanism of action for aripiprazole in neuroinflammatory conditions may also provide new insight into the pathogenesis of ME/CFS.


Health rising blog: Abilify shows promise in retrospective Chronic Fatigue Syndrome (ME/CFS) study, by Cort Johnson

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