An Independent Scientist Award is sought to enable the applicant to devote major effort to mental health treatment research, specifically to the identification, development, and refinement of efficacious and efficient treatments for the most common presenting problems of adult outpatients (e.g, depression, comorbid anxiety and depression, interpersonal problems). The award also is sought to augment the applicant's expertise in treatment research with training in mental health services research, cost-effectiveness evaluation, and advanced statistical techniques. The specific research aim f the award is to conduct two treatment development projects, each on a patient group that is poorly or incompletely responsive to existing treatments that have been found to be efficacious for patients with similar disorders and symptoms. One group is referred to as having "drug resistant depression" (DRD), the other group has a specific pattern of DSM-IV Anxiety and Mood Disorder comorbidity. The ultimate aim of the DRD work is to develop an effective combined cognitive therapy (CT) + drug treatment for DRD. Three immediate aims are to: (1) Extend CT to the treatment of DRD by integrating three existing forms of CT: CT for depression, CT for personality disorders, and CT for anxiety disorders; (2) develop a treatment manual for conducting CT + drug treatment that will optimize the efficacy of combined treatment for DRD, and (3) obtain outpatient pilot outcome data on the combined CT + drug treatment to determine if it merits further investigation in a controlled clinical trial. The second project extends the applicant's prior developmental research on a psychotherapy that integrates cognitive-behavioral anxiety control techniques (ACT) with Interpersonal Psychotherapy for Depression (IPT) for patients with DSM-IV Generalized Anxiety Disorder (GAD) and an independent Major Depressive Episode (MDE). Two central aims are to: (1) Evaluate the effects of two alternative strategies for sequencing the components of ACT + IPT on symptoms of anxiety and depression, and (2) obtain pilot data on ACT + IPT to compare with outcomes of diagnostically and symptomatically matched patients who receive CT at the University of Pennsylvania Center for Cognitive Therapy to evaluate the treatment's potential to have enhanced benefit for GAD + MDE, compared to existing standard treatments.