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Amisulpride (very low dose) From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment'


50 mg daily reduces fatigue and somatic symptoms, and is well tolerated.1


Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study


Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders. We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25mg bid, or fluoxetine 20mg uid; all subjects were un-blinded to the treatment regimen.


At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale. Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated.


Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition

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


Results: Of the 101 patients taking aripiprazole, 75/101 (74%) experienced an improvement in one or more categories: fatigue, brain fog, unrefreshing sleep, and frequency of post-exertional malaise (PEM) episodes, or “crashes.” Twelve individuals (12%) had no observable difference in symptoms at the maximum dose of 2 mg, and 14 individuals (14%) reported worsening of symptoms or onset of side effects that led to discontinuation of the drug


Among the responders, the average fatigue score changed from 5.76 to 2.86 (n = 66, delta = − 2.89, p < 0.001). Similarly, the average brain fog score reduced from 4.39 to 2.06 (n = 66, delta = − 2.33, p < 0.001), and sleep quality ratings changed from 5.80 to 3.75 (n = 60, delta = − 2.05, p < 0.001). Post-exertional malaise was recorded as the time interval, in days, between the onset of each PEM the episode, which was converted to occurrence per day, or 1/(time interval between episodes). The absence of PEM was recorded as “0.” For responders, the average frequency of PEM was 0.24 occurrences per day (or every 4.2 days) before taking the medication and 0.12 occurrences per day (every 8.3 days) while taking aripiprazole (n = 59, p < 0.001). Fifty-seven individuals qualitatively rated the episodes of PEM as milder and shorter in duration and 18 individuals reported a complete resolution of PEM with no new episodes. Improvements in the quality of life enabled six patients to return to work, and four patients reported improvement of their movement disorder (myoclonic dystonia


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


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