This large multisite randomized trial of bipolar patients treated with mood stabilizers compared 3 types of psychotherapy—CBT, FFT, and IPSRT—with a brief psychosocial treatment in hastening recovery from a depressive episode and maximizing the probability of remaining well during a 1-year period. In contrast to previous trials, patients entered the study early in the development of a major depressive episode (mean Montgomery-Asberg Depression Rating Scale score, 21.9) and, thus, may be more representative of the population of bipolar patients seen for acute care in clinical practice.
Given the increasing acceptance of adjunctive psychosocial interventions for bipolar disorder,43,44
we developed a 3-session comparison condition composed of the many common elements found in existing empirically supported treatments rather than choosing a medication-only control. We found that substituting any 1 of the 3 intensive, specialized, manual-driven interventions for this minimal treatment resulted in clinically significant improvements in time to recovery. Overall, patients were 1.58 times more likely to be well in any study month if they received intensive psychotherapy than if they received CC in addition to their pharmacotherapy.
The present results are consistent with those of previous efficacy trials13–15,19,20,23,24
that found that adjunctive psychotherapy delays recurrences in patients with bipolar disorder. Most of these were single-site randomized controlled trials that required therapists to undergo lengthy periods of training and certification and used time-consuming methods of fidelity monitoring. The benefits observed in the present study were achieved across sites with relatively minimal training and low-intensity supervision. Given the limited benefits of antidepressant medications in patients with bipolar depression who are taking mood stabilizers45
(see also G.S.S., A.A.N., J.R.C., et al, unpublished data, 2007), referral for intensive psychosocial treatment seems to be an especially important addition to clinical care.
In secondary analyses we found no differences among the 3 intensive psychosocial treatments in their capacity to aid and sustain recovery. However, the study was underpowered to detect small effect size differences between each of the intensive modalities. With the observed sample size of 293, a type I error rate of 0.05, a Bonferroni adjustment for 3 comparisons, and 80% power, the intensive modalities would have had to differ from each other by an HR of 3.23 to obtain a statistically reliable treatment effect. Moreover, the sample size needed to identify a statistically significant difference between each of the intensive psychosocial treatments and CC based on the smallest observed effect size of 1.34 (CBT vs CC) would be 445 per group. Focused studies of much larger samples are needed to explore whether the potentially meaningful numerical differences observed between the groups are replicable.
The lack of statistically significant differences between the intensive modalities may also reflect the effect of shared components of the treatments, which are in many ways more striking than their differences.23,46,47
Possibly, future studies will combine the most effective components of the modalities and evaluate hybrid models of psychotherapy.48
Patients in the intensive therapies attended fewer than half (mean, 14.3) of the 30 scheduled sessions. This rate is similar to the frequency that bipolar patients typically obtain in randomized trials (mean, 14 sessions), even when study protocols dictate greater frequencies.22,49
Without an attention control, we cannot determine whether these results are attributable to the specific focus of the intensive psychotherapy sessions or simply the greater number of therapist-patient contacts and, by extension, more opportunities to recognize clinical exacerbations and institute rescue strategies. However, there was no main effect of number of sessions and no interactions between treatment modality and number of sessions on time to recovery. Furthermore, a naturalistic study50
of psychotherapy use in the first 1000 patients to enter the STEP-BD indicated that additional sessions of nonspecialized psychotherapy do not necessarily improve outcome.
Consistent with the evidence-based treatment recommendations of the STEP-BD, approximately 80% of the participants received pharmacologic care concordant with national guidelines (E. Dennehy, PhD, written communication, May 9, 2006); however, the STEP-BD guidelines allowed considerable latitude in drug and dosage selection. The intensive psychotherapy and CC groups were balanced at the time of randomization on the proportion of patients taking each type of mood stabilizer, atypical antipsychotic, or adjunctive agent. Furthermore, the 26-week STEP-BD pharmacotherapy study revealed no differences in time to recovery among patients taking mood stabilizers with or without antidepressants (see G.S.S., A.A.N., J.R.C., et al, unpublished data, 2007). Nonetheless, differences between the intensive and nonintensive psychotherapy conditions in drug choice or dosages might have emerged during the 1-year follow-up. Masking psychiatrists to psychosocial treatment assignments might minimize this source of bias in future studies.
Most of the patients were under the care of a psychiatrist and were receiving mood stabilizers at the time of randomization, and a subset (n=236) were willing and eligible to accept randomized treatment without a standard antidepressant agent. Although few participants were treatment naïve and nearly 70% had a history of more than 10 episodes, it is possible that by pairing the entry criteria for a controlled pharmacotherapy study with a psychosocial intervention study we excluded patients who were highly treatment refractory. Consistent with this possibility, patients who participated in the RAD study had better outcomes than those who did not.
Finally, future trials need to examine the cost-effectiveness of psychosocial interventions. Intensive treatments such as IPSRT, FFT, and CBT, although seeming to be more effective than brief treatments in hastening recovery from episodes, maintaining stability, and delaying recurrences, are also more costly. Treatment-associated costs must be carefully balanced against the potential gains for patients in functioning and quality of life and, possibly, reductions in rates of hospitalization or polypharmacy.