Statins in Schizophrenia

Armin Moradi




  • ? Statins to improve clinical outcomes in schizophrenia

Rationale (why care?)

  • Schizophrenia patients have unmet needs
  • Tx not optimal, little effect on negative and cognitive Sx
  • High mortality rate due to CV

Rationale (but…how?)

  • Increased pro-inflammatory cytokines in schizophrenia

Primary Goals

  • Statins good for schizophrenia?


  • Double-blind
  • Randomized
  • Placebo controlled
  • Multicenter (Netherlands)
  • 2 groups
  • 119 participants, 2 groups (statin vs placebo)

Results and Conclusion

  • No dice!

Diving head first!


Funding and Support

  • Stanley Medical Research Institute
  • Dutch Research Council

Conflict of interest

  • No reported conflict of interest


Background and rationale

  • Theoretical foundation laid out
  • Motivation: inflammation

Hypothesis and research question

  • Hypothesis: Statins improve PANSS scores in schizophrenia
  • Primary outcome: PANSS scores after 12 months
  • Secondary outcome: A host of other scales as outlined previously



  • Multicenter, Double-blind, Placebo-controlled, Randomized


  • Adults 18-50 with DSM-IV schizophrenia, schizoaffective, schizophreniform, or psychotic disorder NOS
  • First psychosis within past 3 years
  • Dutch inpatient and outpatient


  • inclusion criteria
    • DSM-IV dx of 295.x or 298.9
    • First onset within 3 years
    • Age 18-50
    • Written informed consent

Screening 2

  • Exclusion criteria
    • Fulfillment of criteria for statin Rx
    • Statin contraindications
    • Chronic use of glucocorticosteroids
    • Chronic use of NSAIDs
    • Current use of statins
    • Pregnancy/breastfeeding
    • Use of CYP3A4 inducer/inhibitor
    • Use of meds that increase risk of rhabdo


  • 127 signed consent, 6 excluded, 2 dropped, 119 randomized
  • 58 placebo, 61 simvastatin
  • 43 placebo completed, 47 simvastatin completed
  • full account of whom terminated at what point


  • pills, same shape, appearance, taste, smell
  • according to prescribing guidelines for simvastatin (qd)


  • Total of 8 visits
  • Each visit:
    • PANSS
    • Metabolic factors
  • Baseline and end
    • Cognitive testing
    • MRI
  • 18 assessments scheduled regularly


  • BACS
  • GAF
  • Physical exam including bloodwork
  • MRI
  • And more…

Statistical Analysis

  • IBM SPSS software
  • Linear mixed model for repeated measurements
  • fixed factors, covariates, etc.
  • time*treatment interaction effect
  • group differences were compared at different timepoints
  • supplementary file with full analysis

Statistical Analysis

  • more analysis!
  • ANCOVA for cognition
  • adherence: used >20% decrease in LDL as reflection of adherence



  • no main effect of simvastatin after 12 months of treatment
  • changed through time
    • significantly lower general PANSS at 6 (P=0.021) and 24 (P=0.040) months
  • dropouts didn't change demographics, & not assoc with scores or illness


  • no difference in cognition after 12 months
  • no main effect for secondary outcomes at 12 months
  • general functioning (GAF) marginally better at 24 months (P=0.052)


  • significantly lowered LDL (P<0.001) and total cholesterol (P=0.000)
  • no change to HDL (P=0.48)
  • more adverse events in the placebo group!
    • myalgia and dark urine reported more in placebo

Clinical Significance

No dice!


  • The good
    • Primary outcome based on objective measures
    • High rate of completion
    • Double blind
    • Similar groups at the start of the study, treated equally except treatment
    • All patients analyzed
  • The bad
    • …not much!

Verdict: Generally Reliable


Statistical Interpretation

Our predefined primary outcome: symptom severity and cognition at 12 months treatment was negative. Previous studies with statins had a shorter treatment duration, which could explain the different findings.

  • There isn't much room for artistic interpretation
  • Both primary and secondary outcomes: large P-value = No significance


  • adherence?
  • good baseline cognitive functioning
  • excluded hypercholesterolmia
  • excluded metabolic syndrome
  • excluded movement disorders


  • Don't use statins for schizophrenia
  • Do use statins to reduce mortality linked to CV disease in schizophrenia


  • Results appropriately interpreted
  • Adequately explained limitations
  • Consistent conclusion
  • Generalizable? No
    • Severity of patients in practice
    • Population across the world
  • Literature correspondence? Yes, explained previous studies
    • Studies with aspirin and celecoxib

Clinical practice

  • No change at this point