ME/CFS is likely to represent a mixed group of conditions, with many different triggers that leads to a common group of symptoms. It has been shown that there is both central and peripheral nervous system involvement and there is emerging evidence that brain inflammation is central to its aetiology. The core symptoms of ME/CFS include debilitating fatigue, unrefreshing sleep, post-exertional malaise, and either cognitive dysfunction or orthostatic intolerance.

With respect to CNS involvement there is evidence from PET scanning that activated cells in the brain are present in patients with ME/CFS. Dopamine appears central to this and Dpoamine D2 receptor agonists can mediate this neuroinflammation. Dopamine modulating drugs could be of use in treating the central nervous system symptoms of ME/CFS.

So, what appears to have happened in this retrospective audit was a team from Stanford used aripiprazole, a pretty potent antipsychotic with an impressive range of potential side effects, in an "off-label" treatment of 101 patients.

This was not a study, no ethics, blinding, crossover, placebo, etc was involved, so it represents a low level of evidence for effect, but is an interesting and impressive set of results all the same.

The age range was from 18 to 84 years old (mean 50 years), with 67% female and 33% male, and the duration of illness was from 1 to 54 years (median 13 years). The duration of aripiprazole therapy ranged from less than one month to 17 months (mean 7.8 months).

For the responders the results were dramatic, 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. In the responders 6 were able to return to work and 4 reported improvement in their movement disorders.

The obvious weakness of this "study" is that it is a retrospective analysis of a group of patients treated with an off-label drug with all the biases that come with this. However, like a lot of studies of this type it gives a clue as to where research should be directed. I'll leave you with the summary from the paper.

"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."

I'll keep an eye on the clinical trials register to see whether a trial is registered this year following the publication of this paper. If so, I'll tag it into the most relevant forums.

For a link to all registered ME/CFS studies -


  • Of label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis: Chron...pdf
    720.6 KB · Views: 73

Get Our Free ME/CFS and FM Blog!

New Threads

Forum Tips

Support Our Work



Shopping on For HR

Latest Resources