Nearly half of the overall population was obese (48%), and slightly less than half (44%) had adipose. Prospective analysis indicated that patients with either obesity or adiposity tended to show less improvement in their CGI scores in a statistically significant way, regardless of which mood stabilizer they were on.
"Part of that might be due to overlapping pathophysiology between bipolar disorder and obesity," Dr. Kemp said. "Much of that is centered around inflammation in the central nervous system, as well as alterations in adipokines receptor levels and mitochondrial dysfunction."
"A key issue is to take care of obesity," said panel discussant Dr. Mauricio Tohen, chairman of psychiatry at the University of New Mexico in Albuquerque. "Regardless of the treatment, when there is obesity, the outcome will not be as good."
Efficacy vs. ‘generalizability’
Adjunctive personalized treatment was measured to help minimize the lack of assay sensitivity and internal validity typically inherent in comparative effectiveness trials, while also achieving more broadly applicable results.
"The right study depends on the right question," Dr. Tohen said. "If the question is whether a particular treatment has efficacy and is safe, then of course, we need an efficacy study. The problem with efficacy studies is that they limit the generalizability."
Instead, Dr. Tohen, who disclosed he spent more than a decade evaluating efficacy studies for both Eli Lily and AstraZeneca (makers of quetiapine), praised the metric of the adjunctive personalized treatments, and said a study should answer the question, "Of all the patients in my clinic, who will do better on which treatment? With efficacy studies you cannot answer that question because of the exclusion criteria that need to be taken into account."
In addition, Dr. Tohen said the metric likely would increase in importance under the Affordable Care Act, where efficacy is not the only consideration. "For example, if a patient relapses earlier, it might not be reimbursed, so asking what other outcomes we need to measure in [these kinds of] comparative effectiveness studies is very important."
In the CHOICE study, which had no placebo group, participating physicians were asked to track each patient’s dosage changes, missed doses, new medications added, discontinued medications, and the specific reasons for any of these changes. Changes that were made because of lack of effectiveness or intolerance were measured; however, planned dosage titrations according to normal scales were not considered necessary clinical adjustments but simply the regular course of treatment.
This heterogeneity of adjunctive treatment was seen by the investigators as a way to reflect "real world" practice, although they also noted it could be seen as a limitation to the study.
Another way the study was designed to reflect real-world practice was the inclusion of a broader-than-usual group of participants, and asking them for their feedback at the end of the study period.
"Before we put together these data, we held a stakeholder summit," Dr. Nierenberg said. "We invited patients and their advocates to help us interpret the study. They felt strongly that this was a reasonably positive study, because they thought that people really did get better. You could report these data toward the negative or the positive, but we reported toward the positive because that is what the stakeholders asked us to do." Dr. Tohen said that this kind of feedback in a comparative effectiveness study was another way these kinds of studies could help guide practice in the era of the Affordable Care Act.
As for who was actually admitted to the study, "exclusions were minimal," said Dr. Edward S. Friedman of the psychiatry department at the University of Pittsburgh. Those with a history of drug or alcohol dependence in the previous 30 days, a demonstrated intolerance to either study drug, or severe cardiovascular or renal disease were excluded, as were those with unstable thyroid disease, and pregnant or breastfeeding women.
Overall, the group was multiethnic, although nearly three-quarters were white and 20% were black. Roughly a third of the entire study population was employed, a third unemployed, and the rest were students, retirees, or those on disability.
The overall BISS score at enrollment averaged 56.1 (SD plus or minus 18.8). The average BISS depression score was 37.6 (SD plus or minus 14.0), and the average BISS mania score was 18.5 (SD plus or minus 12.1).
There were many comorbid psychiatric conditions, ranging from panic disorder to agoraphobia, although substance use was highest (61.4%). Current anxiety disorder also was prevalent at 58%.
"The CHOICE sample was similar in age and gender to previous efficacy studies," Dr. Friedman said. "It was more representative of the U.S. population than efficacy studies such as STEP-BD or LITMUS."