pattismith
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Methylphenidate in COVID-19 Related Brain Fog: A Case Series
Debanjan Bhattacharjee, Surakshitha Poornima H.K., and Avik Chakrabortyhttps://doi.org/10.1177/02537176231222572
Abstract
Limited literature exists regarding specific pharmacological treatments for COVID-19-associated brain fog (BF) syndrome. One previous study using bupropion lacked objectivity. In this multiple baseline case series study, methylphenidate was used in treating post-COVID BF syndrome.Four cases of post-COVID BF syndrome were diagnosed by two psychiatrists after a liaison diagnostic workup with the medical fraternity and treated with methylphenidate (10–30 mg for 1–2 months) resulted in objective improvement as evident by the change in Fatigue Severity Scale (FSS) and Mini Mental Status Examination (MMSE) scores in follow-up compared to baseline. FSS scores were 9 (37–40 at baseline) and MMSE scores were 30 (27–29 at baseline) for all subjects at 3- and 6-month follow-up. No relapse of symptoms was noted at follow-up. Methylphenidate, being a stimulant drug, can be a promising option for BF.
However, this study has a few limitations, like the fact that neuroimaging was not done for all subjects, and studies with a larger sample size are required for a definitive conclusion.
Brain fog (BF) is a common neurocognitive phenomenon often associated with fatigue in post-COVID infection.1,2
In COVID-19 infections, this may result from hypoxia-induced microstructure changes or hyperinflammatory responses.1 Stimulants such as methylphenidate have been reported to be successful in treating fatigue due to non-COVID causes and have been shown to improve associated attention difficulties in a few cases in the literature.3
There is only one observational study of the successful use of bupropion in COVID-19-associated BF syndrome, which is limited due to non-quantitative subjective reporting.4 Here we describe four such cases, which were treated with methylphenidate shown to improve the symptoms of BF as evidenced by objective quantitative measures.
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All patients showed improvement in symptoms subjectively as well as objectively, as evident in the reduction of FSS and MMSE scores compared to baseline within 2–4 weeks (Table 1).
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Methylphenidate, by adjusting the dopamine and norepinephrine levels in the prefrontal cortex,10 yielded an improvement in cognitive functioning in our cases. Bupropion, having a similar mechanism of action as methylphenidate, has been shown to be effective in a previous study,4 which supports our arguments.
Moreover, long COVID cases with cognitive deficits have been reported in the literature are mostly at their 40 or older,1,2 in the contrary our cases are younger, which may be a factor for their faster recovery and little decline in MMSE score at baseline evaluation due to their cognitive reserve. Apart from objectivity, cognitive improvement following intervention in our cases is within weeks (Table 1), which is in contrast to the usual chronicity of non-intervened COVID-19-related BF.1 Though natural remission cannot be overruled, given the drastic improvement after MPH use, the presence of its pro-cognitive mechanism of action, and similar phenomena with other stimulants, favor our argument regarding cognitive improvement in our cases due to MPH use.7
Further, our cases completely recovered with methylphenidate and improvement persisted at follow-up without any extended treatment. Our study has many limitations, like its observational nature, small sample size, absence of a control group, and non-availability of neuroimaging for cases 2 and 4, but it provided objective insight about the effect of stimulants on COVID-19-associated BF syndrome, unlike previous studies.4