Association Between Weight Gain and Remission Status at 3 Months in First-Episode Schizophrenia

To the Editors Weight gain is a well-known and unwanted adverse effect of antipsychotic medication in people with schizophrenia associated with numerous metabolic disorders. Interestingly, findings from several studies as early as the 1950s1,2 have shown weight gain to be associated with symptom improvement. This has brought forth the concept of the “metabolic threshold,” which states that metabolic abnormalities have some role in the clinical efficacy of antipsychotics.3 A recent review examined 15 studies on the association between weight gain and clinical improvement.4 Although most studies reported an association, a key limitation identified was the absence of truly clinically significant improvement such as remission.5 Furthermore, 2 studies, which explored symptom dimensions individually, found the most significant associations with changes in general psychopathology, rather than key symptom constructs of schizophrenia, namely, positive and negative symptoms.6,7 Finally, publication bias was possible—14 of the 15 reviewed studies reported a positive association between weight gain and symptomatic improvement. In this study, we examined the relationship between clinically significant weight gain and symptomatic remission in individuals with first-episode schizophrenia. In line with evidence from previous research, we hypothesized that weight gain would be associated with remission. Participants were recruited from a naturalistic study on first-episode psychosis conducted at the Institute of Mental Health, Singapore. Inclusion criteria were the following: a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder; experiencing their first psychotic episode; and, having less than 4 weeks of antipsychotic treatment prior to study entry. Height and weight were measured at recruitment and at a 3-month follow-up. Antipsychotic prescription information was obtained at 3 months and doses were converted into total daily chlorpromazine equivalents.8 Diagnosis was ascertained using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and psychopathology was rated on the Positive and Negative Syndrome Scale (PANSS). Remission status was defined at 3 months using the proposed criteria by Andreasen et al.5 Clinically significant weight gain was defined as a 7% or more increase from baseline to 3 months. Descriptive statistics compared baseline and follow-up characteristics of remitters and nonremitters. Statistical analyses were performed using the χ2 test for categorical variables, the Student t test for normally distributed continuous variables, and the Mann-Whitney U test for nonnormally distributed continuous variables. The χ2 test was also used to calculate the odds ratio and confidence interval of weight gain compared with remission. The formula by Leucht et al9 was used to calculate the relative (percentage) change in PANSS from baseline to 3 months; this included the total score and the scores for positive symptom, negative symptom, and general pathophysiology subscales. Spearman ρ was used to examine correlation between change in PANSS scores and weight gain. Thirty-one participants were included in this study; 21 (67.7%) achieved symptomatic remission at 3 months. There were no significant differences in demographics, baseline symptom severity, and treatment between nonremitters and remitters (Table ​(Table1). 1). Weight gain was not significantly different between nonremitters and remitters (5.3% vs 8.9%, respectively; P = 0.291); furthermore, the presence of clinically significant weight gain was not significantly associated with remission (odds ratio, 2.12; confidence interval, 0.43–10.52). Weight gain was inversely correlated with change in general psychopathology subscale (r = −0.363, P = 0.044), and change in total PANSS score (r = −0.419, P = 0.019), but not with positive (r = −0.261, P = 0.157) and negative (r = 0.251, p = 0.197) subscales. TABLE 1 Characteristics of Study Sample