Greater depression severity at baseline generally predicts a poorer response to pharmacotherapy35 and/or psychotherapy.36 Duration of the index episode and the number of prior episodes are the strongest baseline predictors of the subsequent well interval.35,37-41 The presence of Axis I comorbidity, both at the syndromal and the subsyndromal level, impedes the achievement of full remission. Panic or anxiety symptoms or disorder are particularly pernicious in

this respect.42-45 Axis II comorbidity has also been found by numerous investigators to be associated with incomplete remission of depression.35,46-48 Inhibitors,research,lifescience,medical To some extent, the association of both of these forms of comorbidity (Axis I and Axis II) with incomplete remission may represent an artifactual inflation of depression rating scale scores via the presence of symptoms associated with the Axis I or Axis II condition. However, there also are well-articulated descriptions of how, for example, anxiety disorders or subsyndromal anxiety conditions and Axis II conditions might interfere with obtaining the full Inhibitors,research,lifescience,medical benefit from a treatment Inhibitors,research,lifescience,medical such as CT or IPT49 More recently, Katon and colleagues50,51 have focused on the extent to which

medical comorbidities, such as diabetes (Axis III conditions), may interfere with remission of depression. Again, some of this may be artifact caused by inflation of depression scores or by somatic symptoms associated with a comorbid medical condition. On the other hand, there are specific hypothesized routes through which medical comorbidity might interfere with either pharmacotherapy or psychotherapy. Somatic preoccupation may preclude the individual’s ability to focus on the specific work involved in the psychotherapy, whereas the medical condition or the pharmacological treatment Inhibitors,research,lifescience,medical of the medical condition may interfere with the metabolism of antidepressant pharmacotherapy. Finally, failure to adhere to the requirements of either a pharmacotherapeutic or a psychotherapeutic regimen can

certainly interfere with the achievement of full remission of symptoms. Psychotherapy and pharmacotherapy combinations Inhibitors,research,lifescience,medical and sequences also have a clear Thiamine-diphosphate kinase role in the prevention of recurrence, another key goal of treatment of unipolar disorders. Since we now recognize that the majority of unipolar depressions are recurrent, perhaps the most challenging part of depression treatment is that which find more focuses on the prevention of relapse and recurrence. As we describe below, it is here that pharmacotherapy-psychotherapy combinations and sequences have shown themselves to be particularly valuable approaches to treatment. Combination acute treatment: achieving remission and return of function As noted above, efforts to achieve full remission and return of function have encompassed the evaluation of combination therapy in comparison with either pharmacotherapy or psychotherapy monotherapy as well as treatment sequences.