Enrichment-discontinuation designs in psychiatric drug maintenance therapy

Abstract

Objective. This thesis tests the validity of a randomized controlled trial variant, the enrichment-discontinuation design (also called a randomized discontinuation design) against gold-standard classic RCT's using published trials of psychiatric drug therapy. Methods. A series of systematic reviews were conducted to identify all maintenance trials of mood stabilizers and antidepressants. Planned comparisons between enrichment discontinuation trials and gold standard classic RCT's were conducted. Finally, a sample of research literature was reviewed to identify the extent to which the limits of enrichment discontinuation trials were identified. Results. There was a non-statistically significant trend favoring drugs used in open phases vs classic RCT's. The lack of extended classic RCT's of psychiatric drugs is poorly recognized. Conclusion. Enrichment discontinuation designs dominated the evidence base supporting psychiatric drug maintenance. Bias cannot be ruled out. Limits to the design are poorly recognized in the literature. For further details, refer to the executive summary.