A placebo-controlled randomized clinical trial of amantadine hydrochloride for evaluating the functional improvement of patients following severe acute traumatic brain injury.

BACKGROUND: Considering the known derangements in the dopaminergic neurotransmitter systems following traumatic brain injury (TBI), dopamine agonists are used as a pharmacologic option. In this study, we evaluate the effects of amantadine hydrochloride on the functional improvement of severe TBI patients. METHODS: Within a triple-blinded (patients, intervention administrators, and outcome assessors) placebo-controlled randomized clinical trial, we evaluated the effects of amantadine (100 mg BD (twice a day) for 14 days, then 150 mg BD for another 7 days, and 200 mg BD for another 21 days) on outcome measurements of weekly mean Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS), through six weeks of trial for 57 patients (29 amantadine, 28 placeboes) with severe TBI admitted in our hospital. RESULTS: Although both groups had improvement in their DRS, the change from baseline was significantly better in the amantadine group (10.88±5.24 for amantadine vs. 8.04±4.07 for placebo, P=0.015). No significant difference was observed between groups for GOS (1.04±0.55 for amantadine vs. 1.12±1.05 for placebo, P=0.966). CONCLUSIONS: Based on our findings, amantadine hydrochloride might improve the speed of functional ability improvement in severe TBI patients, evaluated by DRS, and is also well tolerated by patients. Although, there were some limitations in this study, including small sample size, short time interval, not providing a wash-off period and invalidity of GOS for measuring recovery rates in short-term periods.

Cilostazol as an adjunctive treatment in major depressive disorder: a pilot randomized, double-blind, and placebo-controlled clinical trial.

BACKGROUND: Cilostazol, a phosphodiesterase-3 inhibitor, has been reported to improve depressive-like behavior in experimental studies of depression. We investigated the safety and efficacy of cilostazol combination therapy with sertraline in treating patients with major depressive disorder (MDD) in a 6-week, parallel, randomized controlled trial. METHOD: Among patients referred to the outpatient clinic of a tertiary hospital, those with a diagnosis of MDD with moderate to severe severity (a score of >19 on the Hamilton depression rating scale (HAM-D)) were enrolled. A total of 54 MDD patients aged 18-65 years were randomly assigned to either the cilostazol (100 mg daily) or the placebo group. Both groups received sertraline 100 mg per day similarly. Changes in HAM-D at weeks 2, 4, and 6 were the primary outcome. Participants and outcome assessors were blinded. RESULTS: At week 6, patients in the cilostazol group had significantly lower HAM-D score (p value= 0.015). General linear model repeated-measure analysis showed significant effect for treatment in improving MDD severity (p value <0.001). The remission rate at the study endpoint and number of responders at week 4 were significantly higher in the cilostazol group (p value= 0.047, p value= 0.032, respectively). The cilostazol group demonstrated a significantly shorter time to response. No significant difference was observed in treatment response at the study endpoint, and there were no serious adverse effects. CONCLUSION: Our study supports safety and efficacy of cilostazol in treating MDD patients. TRIAL REGISTRATION: This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir ; registration number: IRCT20090117001556N130).