Simvastatin augmentation for recent-onset psychotic disorder: A study protocol

• Low-grade inflammation is possibly involved in the pathophysiology of schizophrenia.
• Beneficial effects of simvastatin addition: double-blind, placebo-controlled trial
• 250 patients with recent-onset psychosis: simvastatin 40 mg/day or placebo, 1 year
• Primary outcome measures: symptom severity and cognitive performance
• Secondary outcome measures: brain volume loss, metabolic and inflammatory parameters

BackgroundThere is ample evidence that inflammatory processes play a role in the pathophysiology of schizophrenia. Randomized controlled trials have shown benefit of some (but not all) anti-inflammatory drugs on symptom severity. So far, these drugs have been given for a relatively short period. Simvastatin combines well-established vascular protection with reduction of the inflammatory status of the brain, thus offering an attractive potential to further improve treatment of schizophrenia and related disorders.Methods/designWe are currently undertaking a double-blind placebo-controlled trial, including 250 patients (18–50 years of age) whom are diagnosed with a schizophrenia spectrum disorder. Onset of their first psychosis should be no longer than three years ago. Patients are randomized 1:1 to either 40 mg simvastatin or placebo daily during one year, next to their regular antipsychotic treatment. Primary outcome measures are symptom severity and cognitive decline as measured by the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), at baseline and end of treatment. Secondary aims are to establish an attenuation of brain tissue loss and an improvement in general functioning, presence and severity of metabolic syndrome and degree of movement disorders. Lastly, immunological and metabolic parameters are assessed in blood samples to possibly predict treatment response.DiscussionWe hypothesize simvastatin to lower symptom severity and to prevent or reduce excessive brain tissue loss and cognitive decline, compared to placebo. We expect that simvastatin will be well-tolerated and lead to decreased prevalence of metabolic syndrome.Trial registrationClinicalTrails.gov NCT01999309; EudraCT-number 2013-000834-36.