Statins have been shown to decrease depressive symptoms in certain groups of 
patients, an effect that is mostly attributed to their anti-inflammatory and 
neurotransmitter modulatory potentials. We aimed to investigate the 
antidepressant effects of simvastatin as an adjuvant therapy in patients with 
moderate to severe depression. In this double-blind placebo-controlled clinical 
trial, 48 patients were randomly allocated to receive simvastatin or placebo as 
an adjunct to fluoxetine for six weeks. Patients were evaluated with the 
Hamilton Depression Rating Scale (HDRS) at baseline and weeks 2, 4 and 6. 
Probable clinical and laboratory adverse events were also monitored and compared 
between the two groups. Simvastatin-treated patients experienced significantly 
more reductions in HDRS scores compared to the placebo group by the end of the 
trial (p=0.02). Early improvement and response rates were significantly greater 
in the simvastatin group than the placebo group (p=0.02 and p=0.01, 
respectively) but remission rate was not significantly different between the two 
groups (p=0.36). No serious adverse event was reported during this trial. In 
conclusion, simvastatin seems to be a safe and effective adjuvant therapy for 
patients suffering from major depressive disorder. However, more confirmatory 
studies are warranted.