Moderators of behavioral activation versus treatment as usual effects on negative symptoms in patients with...

Recent work supports the efficacy of Behavioral Activation (BA) over Treatment as Usual (TAU) for the negative symptoms (NS) of Schizophrenia Spectrum Disorder (SSD). To inform precision medicine approaches, we aimed to identify factors that moderate the effect of BA versus TAU. We performed discovery-based moderators analyses, leveraging data from a recently completed randomized controlled trial that found BA had efficacy over TAU for NS. Potential moderators were pre-treatment symptom items from common symptom scales, including items from the Clinical Assessment Interview for Negative Symptoms [13], the Positive and Negative Syndrome Scale [14] (PANSS), and the Brief Negative Symptom Scale. Seven PANSS items emerged as potential negative moderators, wherein greater severity of these symptoms was associated with lower efficacy of BA versus TAU (effect size estimate range: -0.45 to -0.25). These negative moderators were conceptual disorganization, hallucinatory behavior, grandiosity, anxiety, tension, uncooperativeness, and unusual thought content. Using total scores on these items as a combined moderator revealed a minority subgroup, composed of 20% of the overall sample, in whom rates of response to TAU and BA were roughly equal (response rates: TAU, 60%; BA, 50%). In contrast, among the majority subgroup (80% of the sample), BA had clear effects above and beyond the TAU condition (response rates: TAU, 20%; BA, 58%). These findings showcase how moderator research informs precision medicine. Specifically, NS appear malleable by adding BA to TAU among patients without uncooperativeness, anxiety, and positive symptoms. However, in the presence of these moderating symptoms, TAU may be equally efficacious.