Adults 18-50 with DSM-IV schizophrenia, schizoaffective, schizophreniform, or psychotic disorder NOS
First psychosis within past 3 years
Dutch inpatient and outpatient
Screening
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
Participants
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
Administration
pills, same shape, appearance, taste, smell
according to prescribing guidelines for simvastatin (qd)
Assessment
Total of 8 visits
Each visit:
PANSS
Metabolic factors
Baseline and end
Cognitive testing
MRI
18 assessments scheduled regularly
Measures
PANSS
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
Results
One
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
Two
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)
Three
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!
Reliability
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
Conclusion
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
Limitations
adherence?
good baseline cognitive functioning
excluded hypercholesterolmia
excluded metabolic syndrome
excluded movement disorders
Conclusion
Don't use statins for schizophrenia
Do use statins to reduce mortality linked to CV disease in schizophrenia
Discussion
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