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

Abstract

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. 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 [4–6]. 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 a retrospective study, we reviewed the medical records of 101 patients who met the criteria for a ME/ CFS diagnosis according to three separate case definitions (Fukuda, CCC, and IOM) and who received off-label aripiprazole (Table 1). Medical records were included for individuals evaluated in the clinic at least twice, representing periods before and after the use of the medication. The age range was from 18 to 84 years old (mean 50 years), with a gender distribution of 67% female and 33% male, and the duration of illness was from 1 to 54 years (median 13 years). The daily oral dose of aripiprazole ranged from 0.2 to 2.0 mg/day (mean 1.1 mg/ day). Dosage started at 0.25 mg/day and titrated up or down based on each patient’s observations and feedback. The duration of aripiprazole therapy ranged from less than one month to 17 months (mean 7.8 months). Patient records were also evaluated for concurrent use of various classes of antidepressants, including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine Open Access Journal of Translational Medicine