• psychological treatment;
  • bipolar disorder;
  • depression;
  • anxiety disorder;
  • mediators;
  • moderators;
  • outcome

Studies that combine pharmacotherapy with psychological treatment for the mood and anxiety disorders must consider the role of moderators (pretreatment variables that specify the conditions under which treatments are effective) and mediators (change mechanisms in the causal pathways between treatments and outcomes) in explaining the impact of experimental treatments. This article gives examples of the kinds of moderators and mediators—both psychosocial and biological—that are important to examine in combination treatment studies. It conceptualizes outcome as involving multiple domains, including mood and anxiety symptoms, life functioning, and illness costs. Research should also examine the appropriate sequencing of pharmacological and psycho-social interventions and how this sequencing may vary from disorder to disorder.