Table 3. Comparison of studies conducted in humans with MS.

YOP: year of publication; MS: multiple sclerosis; SSRI: selective serotonin reuptake inhibitor; RCT: randomized controlled trial

Title of the study	Author	YOP	Study design	Number of patients	Purpose of the study	Conclusions
The effect of fluoxetine on progression in progressive multiple sclerosis: a double-blind, randomized, placebo-controlled trial	Mostert et al. [31]	2013	RCT	42	Evaluate the ability of fluoxetine to modify clinical and radiologic parameters in patients with progressive MS	No significant clinical or radiologic improvement was detected in the fluoxetine-treated group in comparison with the control
Association between the use of selective serotonin reuptake inhibitors and multiple sclerosis disability progression	Zhang et al. [34]	2016	Case-control	3,920	Determine if the exposure to SSRI is associated with a slow rate of disability in MS patients	No association was found between the use of SSRI and a slower disability accumulation rate
Fluoxetine in progressive multiple sclerosis: the FLUOX-PMS trial	Cambron et al. [32]	2019	RCT	136	Determine if treatment with fluoxetine could slow the progression of progressive MS	No significant difference in clinical scores or imaging findings were found between the two compared groups
Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT	De Angelis et al. [33]	2020	RCT	440 was the target sample size, only 111 were taking fluoxetine	Determine whether fluoxetine could decrease the brain atrophy rate in progressive MS patients	No difference in brain loss percentage between the patients taking fluoxetine and the controls