Simvastatin Addition for Patients With Recent-onset Schizophrenia

Summary

Rationale: There is ample evidence that inflammatory processes play a role in the pathophysiology of schizophrenia. Although Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been shown to be able to reduce symptoms in these patients, these drugs either have unfavourable cardiovascular side effects or are otherwise not well tolerated. Moreover, patients with schizophrenia already tend to have an increased cardiovascular risk. The combination of well-established vascular protection and reduction of inflammation by simvastatin offers a highly attractive potential to further improve the treatment of schizophrenia and related disorders. Hypotheses: Daily treatment with 40mg simvastatin in addition to antipsychotic treatment reduces psychotic symptoms, improves cognition, attenuates brain volume loss, and decreases the risk for metabolic syndrome as well as for movement disorders, when compared to placebo. Objective: The primary objective of this trial is to investigate the proposed beneficial effect of simvastatin as compared to placebo when given for one year in addition to antipsychotic medication to patients with psychotic disorder. We expect lower symptom severity as measured with the PANSS (Positive and Negative Syndrome Scale) and less cognitive decline as measured with the BACS (Brief Assessment of Cognition in Schizophrenia).Secondary objectives are assessment of general functioning, presence and severity of metabolic syndrome and degree of movement disorders, and assessments of brain volume. Lastly, we examine various immunological parameters in serum and peripheral blood mononuclear cells and the experience of childhood trauma. Study design: Randomized placebo-controlled double-blind trial. Study population: 150 men and women, between 18 and 50 years of age, diagnosed with schizophrenia, schizoaffective or schizophreniform disorder (DSM-IV 295.\*) or psychosis NOS (not otherwise specified) (298.9). Onset of first psychosis no longer than 3 years ago. Intervention: Patients will be randomized 1:1 to either 40 mg simvastatin or placebo daily, in the form of identical tablets.

Timeline

Start

2013-10

Primary completion

2019-12-19

Completion

2019-12-19

Publications

• Zaki JK, Lago SG, Spadaro B, Rustogi N, Gangadin SS, Benacek J, Drexhage HA, de Witte LD, Kahn RS, Sommer IEC, Bahn S, Tomasik J. Exploring peripheral biomarkers of response to simvastatin supplementation in schizophrenia. Schizophr Res. 2024 Apr;266:66-74. doi: 10.1016/j.schres.2024.02.011. Epub 2024 Feb 19.
• Begemann MJH, Schutte MJL, van Dellen E, Abramovic L, Boks MP, van Haren NEM, Mandl RCW, Vinkers CH, Bohlken MM, Sommer IEC. Childhood trauma is associated with reduced frontal gray matter volume: a large transdiagnostic structural MRI study. Psychol Med. 2023 Feb;53(3):741-749. doi: 10.1017/S0033291721002087. Epub 2021 Jun 3.
• Begemann MJ, Schutte MJ, Slot MI, Doorduin J, Bakker PR, van Haren NE, Sommer IE. Simvastatin augmentation for recent-onset psychotic disorder: A study protocol. BBA Clin. 2015 Jul 3;4:52-58. doi: 10.1016/j.bbacli.2015.06.007. eCollection 2015 Dec.

Drugs

Indications