A randomized pilot study of psychotherapy and quetiapine for the acute treatment of bipolar II depression

Bipolar (BP) II disorder is a highly recurrent disorder (1) associated with elevated levels of psychosocial impairment (2, 3), disability (4), comorbidity (3, 5), and suicidal ideation/behaviors (6, 7) . Despite the significant suffering associated with BP-II disorder, relatively little is known about how best to treat this illness (8). Uncertainty about management of BP-II is complicated by the fact that depression is the dominant pole of BP-II disorder (1), a phase of the disorder for which we have relatively few effective treatments (9, 10). Despite the large side effect burden associated with medications used to treat BP disorders (8, 11) and the large lacunae in the evidence base with respect to their efficacy (12), alternatives to pharmacotherapy are rarely considered in mainstream treatment algorithms (8, 13). Psychotherapy, which arguably has no side effects (14), may play an important role in the management of BP-II disorder as many individuals suffering from the illness struggle with issues that lend themselves to psychosocial remediation. For instance, recognition and treatment of BP-II disorder often lags years behind initial manifestation of symptoms (15), a problem which is associated with a chronic course of illness (1) and subsequent erosion in psychosocial functioning (2, 4). Further, individuals with BP-II disorder typically have difficulty distinguishing among rapid mood shifts and subtle mood states (i.e., hypomania) that characterize BP-II (16), and yet ability to recognize mood symptoms likely constitutes the first step toward effective disease management. Bipolar-specific psychotherapies can provide patients with strategies for understanding their illness, managing symptoms, and enhancing psychosocial functioning (17, 18). Although use of psychotherapy alone as an alternative to pharmacotherapy is likely contraindicated in BP-I disorder, it is not unreasonable to consider this approach in BP-II disorder where individuals are at low risk of experiencing fully syndromal manic episodes or psychosis. Despite the compelling argument to be made for its inclusion in the therapeutic armamentarium for BP-II disorder, the literature on psychotherapy for the treatment of BP-II disorder is sparse. When used in combination with mood stabilizers, bipolar-specific psychotherapies have been shown to shorten time to recovery in patients suffering from BP disorders, including a subset of individuals diagnosed with BP-II disorder (19). A small group of individuals meeting criteria for BP-II disorder who received group psychoeducation in addition to pharmacotherapy had better long term (five year) outcomes than patients receiving a control psychosocial intervention (20). We have previously demonstrated feasibility of treating patients meeting criteria for BP-II depression with psychotherapy alone (21). There are no comparative trials of psychotherapy and pharmacotherapy. Interpersonal and Social Rhythm Therapy (IPSRT) is an evidence-based psychotherapy for bipolar disorder (22). In randomized clinical trials where IPSRT was used in combination with medication, IPSRT has been shown to reduce time to recovery from an episode of depression (19), decrease the likelihood of mood episode recurrence (23), and improve psychosocial and occupational functioning (24, 25). We have modified IPSRT for use as monotherapy with individuals who have BP-II disorder (16, 21). In order to advance understanding of the roles of psychotherapy and pharmacotherapy in the management of BP-II depression, we conducted a small randomized trial of IPSRT versus quetiapine, a second generation antipsychotic that has demonstrated efficacy as treatment for BP-II depression (26–28). The primary goal was to evaluate the feasibility and acceptability of this approach. A secondary goal was to examine symptomatic and functional outcomes over a 12-week period in patients assigned to the two treatment conditions.