Strengths and Limitations
MDD, TRD, mood disorders
SECONDARY
Our study has both strengths and limitations. The relatively large sample size and high retention rates (93% overall) are strengths of this study; we had the power to detect a medium antidepressant ES for simvastatin. The pragmatic design and low-resource, community setting are additional strengths of our trial. Most RCTs of pharmacotherapies, including antidepressants and statins, are conducted in high-income countries, limiting their international representativeness.This study also has some limitations. The use of standard care is a potential limitation of our study. However, given the severity of MDD in the TRD sample recruited, it would have been challenging to standardize treatment in our community outpatient participants. Although most participants were receiving combination treatments involving antidepressants, mood stabilizers, atypical antipsychotics, and anxiolytic medications, these pharmacotherapies were similar across groups throughout the trial. Furthermore, we conducted a post hoc secondary analysis and found that the number of baseline psychotropic medications did not impact the estimates of the treatment effect.As in most previously published RCTs of mood disorders, our placebo group experienced a large antidepressant response. We have previously suggested that the nonspecific therapeutic effects of attentive measurement-based care through repeated study visits in a clinical trial contribute to the placebo response,