Longitudinal effect of clozapine-associated sedation on motivation in schizophrenia: naturalistic longitudinal study

Negative symptoms of schizophrenia manifest as reduced motivation and pleasure (MAP) and impaired emotional expressivity (EXP). These can occur as primary phenomena, but have also been suggested to occur secondary to other clinical factors, including antipsychotic-induced sedation. However, this relationship has not been established formally. Here, we examined the effect of antipsychotic-induced sedation (assessed via the proxy of total daily sleep duration) on MAP and EXP in a cohort of 187 clozapine-treated patients with schizophrenia followed for over 2 years on average, using multilevel regression and mediation models. MAP, but not EXP, was adversely influenced by sedation, independently of the severity of psychosis or depression. Moreover, clozapine impaired MAP indirectly by worsening sedation, but after accounting for clozapine-induced sedation, clozapine improved MAP. Our results highlight the importance of addressing sedative side-effects of antipsychotics to improve clinical outcomes.

Automated summary

Negative symptoms of schizophrenia, such as reduced motivation and impaired emotional expressivity, can be influenced by antipsychotic-induced sedation. This study found that sedation adversely affected motivation but not emotional expressivity in clozapine-treated patients. Clozapine also indirectly impaired motivation through worsening sedation, but after considering sedation, it improved motivation. These findings emphasize the importance of addressing sedative side-effects of antipsychotics for better clinical outcomes.