Efficacy of Fluoxetine for Post-Ischemic Stroke Depression in Tanzania.

OBJECTIVE: Post-stroke fluoxetine trials are primarily conducted in high-income countries. We characterize post-ischemic stroke depression in fluoxetine-treated and -untreated study participants in urban Tanzania. METHODS: Adults (>18 years old) within 14 days of CT-confirmed acute ischemic stroke onset were enrolled at Muhimbili National Hospital, Tanzania. The fluoxetine-treated group took 20mg fluoxetine daily for 90 days in a phase II trial and were compared to fluoxetine-untreated historical controls. The primary outcome was depression at 90 days, measured by the Patient Health Questionnaire-9 (PHQ-9). PHQ-9 scores were compared between fluoxetine-treated and -untreated groups. A score >=9 points was considered to reflect depression. A multivariable linear regression model assessed associations with post-stroke PHQ-9 scores. RESULTS: Of the fluoxetine-treated (n=27) and -untreated (n=32) participants, the average age was 56.8 years old (39% women, 100% Black/African). The average presentation NIHSS score was 12.1 points and modified Rankin Scale (mRS) score was 3.5. The average mRS score at 90-day follow-up was 2.3. There was no significant difference between 90-day PHQ-9 scores in the fluoxetine-treated (mean=4.1 points, standard deviation=3.2; 11% depression) and untreated (mean=4.4, standard deviation=4.8; 19% depression) groups, p=.69. In the multivariable analysis, older age (ß=0.08, p=.03) and higher NIHSS score (ß=0.15, p=.04), but neither fluoxetine (ß=0.57, p=.59) nor sex (ß=-0.51, p=.63), were significantly associated with more depressive symptoms. CONCLUSIONS: Our findings parallel results from trials from higher income settings that fluoxetine does not significantly improve post-ischemic stroke depression, although our sample size was small. More work is needed to depict the longitudinal nature and treatment of post-stroke depression in Sub-Saharan Africa.

Measuring Ambulation, Motor, and Behavioral Outcomes with Post-stroke Fluoxetine in Tanzania: The Phase II MAMBO Trial.

We test the safety of fluoxetine post-ischemic stroke in sub-Saharan Africa. Adults with acute ischemic stroke, seen <14 days since new-onset motor deficits, were enrolled from November 2019 to October 2020 in a single-arm, open-label phase II trial of daily fluoxetine 20 mg for 90 days at Muhimbili National Hospital, Dar es Salaam, Tanzania. The primary outcome was safety with secondary outcomes of medication adherence and tolerability. Thirty-four patients were enrolled (11 were female; mean age 52.2 years, 65% < 60 years old; mean 3.3 days since symptom onset). Participants had hypertension (74%), diabetes (18%), and smoked cigarettes (18%). The median National Institutes of Health Stroke Scale score at enrollment was 10.5. The median Fugl-Meyer Motor Scale score was 28.5 (upper extremity 8, lower extremity 17.5). 32/34 participants (91%) survived to 90 days. There were eight serious and two nonserious adverse events. Deaths occurred due to gastrointestinal illness with low serum sodium (nadir 120 mmol/L) with seizure and gastrointestinal bleed from gastric cancer. The average sodium level at 90 days was 139 mmol/L (range 133-146) and alanine transaminase was 28 U/L (range 10-134). Fluoxetine adherence was 96%. The median modified Rankin Scale score among survivors at 90 days was 2 and Fugl-Meyer Motor Scale score was 66 (upper extremity 40, lower extremity 27). Median 90-day Patient Health Questionnaire-9 and Montgomery-Åsberg scores were 3.5 and 4 (minimal depression). Fluoxetine administration for 90 days poststroke in sub-Saharan Africa was generally safe and well-tolerated, but comorbid illness presentations were fatal in 2/34 cases, even after careful participant selection.