TY - JOUR
T1 - The role of weight gain in explaining the effects of antipsychotic drugs on positive and negative symptoms
T2 - An analysis of the CATIE schizophrenia trial
AU - Bellavia, Andrea
AU - Centorrino, Franca
AU - Jackson, John W.
AU - Fitzmaurice, Garrett
AU - Valeri, Linda
N1 - Funding Information:
This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102 , PI: LV) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health.
Funding Information:
This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102, PI: LV) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. We are indebted to Hardeep Ranu and Garry Gray, both from the Harvard Catalyst Reactor Program, for project facilitation and support; Marsha Wilcox, Janssen Scientific Director & Fellow, for making this study possible; and to the other Harvard Catalyst funded researchers using these data (Sharon-Lise Normand and Jacob Spertus).
Publisher Copyright:
© 2018
PY - 2019/4
Y1 - 2019/4
N2 - Second-generation antipsychotics are associated with moderate benefits in terms of improved schizophrenia symptoms, but also with higher rates of side-effects such as excessive weight gain (WG); a consensus on their efficacy has not been reached. To date, no study has evaluated the interplay of treatments and side-effects in a single framework, which is a critical step to clarify the role of side-effects in explaining the efficacy of these antipsychotics. We used recent methods for mediation and interaction to clarify the role of WG in explaining the effects of second-generation drugs on schizophrenia symptoms. We used data from 1460 participants in the CATIE trial, assigned to either perphenazine (first-generation comparison drug), olanzapine, quetiapine, risperidone, or ziprasidone. The primary outcome was an individual's score on the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia after 9 months, separately evaluated as positive (PANSS+), negative (PANSS−), and total PANSS score. WG after 6 months was investigated as a potential mediator and effect modifier. Results showed that, by limiting WG, patients would benefit of a considerably better improvement in terms of PANSS symptoms. In the scenario of weight change being controlled between −2% and 1% for all participants, patients assigned to olanzapine would experience the highest significant improvements in both PANSS+ (−2.66 points; 95% CI: −4.98, −0.35), PANSS− (−1.59; 95% CI: −4.31, 1.14), and total PANSS (−6.11; 95% CI: −13.13, 0.92). In conclusion, occurrence of excessive WG hampers the potentially beneficial effects of second-generation antipsychotics, thus suggesting future directions for treatment and interventions.
AB - Second-generation antipsychotics are associated with moderate benefits in terms of improved schizophrenia symptoms, but also with higher rates of side-effects such as excessive weight gain (WG); a consensus on their efficacy has not been reached. To date, no study has evaluated the interplay of treatments and side-effects in a single framework, which is a critical step to clarify the role of side-effects in explaining the efficacy of these antipsychotics. We used recent methods for mediation and interaction to clarify the role of WG in explaining the effects of second-generation drugs on schizophrenia symptoms. We used data from 1460 participants in the CATIE trial, assigned to either perphenazine (first-generation comparison drug), olanzapine, quetiapine, risperidone, or ziprasidone. The primary outcome was an individual's score on the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia after 9 months, separately evaluated as positive (PANSS+), negative (PANSS−), and total PANSS score. WG after 6 months was investigated as a potential mediator and effect modifier. Results showed that, by limiting WG, patients would benefit of a considerably better improvement in terms of PANSS symptoms. In the scenario of weight change being controlled between −2% and 1% for all participants, patients assigned to olanzapine would experience the highest significant improvements in both PANSS+ (−2.66 points; 95% CI: −4.98, −0.35), PANSS− (−1.59; 95% CI: −4.31, 1.14), and total PANSS (−6.11; 95% CI: −13.13, 0.92). In conclusion, occurrence of excessive WG hampers the potentially beneficial effects of second-generation antipsychotics, thus suggesting future directions for treatment and interventions.
KW - Antipsychotics
KW - Interaction
KW - Mediation
KW - PANSS score
KW - Weight gain
UR - http://www.scopus.com/inward/record.url?scp=85058792222&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058792222&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2018.12.006
DO - 10.1016/j.schres.2018.12.006
M3 - Article
C2 - 30584025
AN - SCOPUS:85058792222
SN - 0920-9964
VL - 206
SP - 96
EP - 102
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -