Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

Abstract

<b><i>Introduction:</i></b> Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. <b><i>Methods:</i></b> We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck’s Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. <b><i>Results:</i></b> Clinical scores decreased in both groups (<i>p</i> = 0.0001); Beck’s presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (<i>p</i> < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. <b><i>Conclusion:</i></b> Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.

Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association

“…Numerous studies reported the effects of lipid-lowering therapies on the risk of dementia and impaired cognition (Table 4) 2,7,127–154 and for the treatment of dementia (Table 5). 155–168 Most of the higher-quality studies explored whether LDL-C–lowering therapies affected cognition.…”

Statin for mood and inflammation among adult patients with major depressive disorder: an updated meta-analysis

“…Of the seven included studies, all were completed and reported clinical outcomes ( 17 – 23 ). Six RCTs enrolled patients with MDD ( 17 – 20 , 22 , 23 ), while one enrolled patients with MDD or BD ( 21 ). One RCT enrolled patients with a history of coronary artery bypass surgery in the last 6 months ( 20 ).…”

“…Most studies administered simvastatin and atorvastatin for 6–12 weeks ( 18 – 21 , 23 ). The primary endpoint was depression (indicated by HDRS score) in six RCTs ( 17 – 20 , 22 , 23 ).…”

“…The mean age at MDD onset was 32.5 years, and 56.5% of patients were experiencing their first MDD episode. Only two RCTs reported baseline cognition ( 21 , 22 ). The mean levels of TC, LDL, HDL, and TG were 168.4, 97.4, 50.1, and 115.5 mg/dl, respectively.…”

“…All RCTs used concealed treatment allocation methods ( 17 – 23 ). Four RCTs reported the methods used to blind participants and personnel ( 19 – 21 , 23 ), and six RCTs reported the methods used for blinding of outcome assessments ( 17 – 20 , 22 , 23 ). The attrition bias and selective reporting bias were low in all except one RCT ( 21 ) ( Figure 2 ).…”