Personalized Indications for Cognitive Behavioural Therapy and Antidepressants in the Treatment of Major Depressive Disorder and Persistent Depressive Disorder

Depression is among the most common and burdensome diseases worldwide and in Canada. It is treatable with effective pharmacological and psychological treatments, but fewer than 50% of individuals achieve remission with the first treatment. The unsatisfactory outcomes are at least partly due to a gap in evidence on which treatment benefits which individual.

The two most commonly used treatment modalities for depression are antidepressant medication and psychotherapy. However, only a minority of individuals with depression achieve remission with each type of treatment. On average, combination of antidepressants and psychotherapy achieves better results than either alone, but using two treatments at the same time may be wasteful and unnecessary. Several lines of evidence suggest that the apparently superior results of combination may be due to some individuals preferentially responding to antidepressants and others to psychological treatment. These findings point to the possibility that it may be possible to improve outcomes of depression by matching psychological and pharmacological treatment to individuals who are most likely to benefit from each one. The investigators propose to close this gap using a combination of clinical predictors and biomarkers to optimize the choice between psychological and pharmacological treatment.

The investigators have identified that a symptom profile with prominent reduction in interest and activity, history of maltreatment in childhood, increase in systemic inflammation, and a genetic variant increasing sensitivity to environment predict poor response to antidepressant medication. Indirect evidence suggests that the same factors may predict better response to cognitive-behavioural psychotherapy.

The investigators focus on these four predictors with substantial prior evidence:

Reduced interest and activity. A symptom dimension of interest and activity emerged as the strongest predictor of poor outcome of antidepressant medication treatment. This prediction replicated with undiminished effect size in the largest study of antidepressant treatment carried out to date,4 and additional independent replications confirmed its robustness. Cognitive behavioural therapy improves activity and interest better than antidepressant medication.