Activating and Tranquilizing Effects of First-Time Treatment with Aripiprazole, Olanzapine, Quetiapine, and Risperidone in Youth

Abstract

Objective: To assess activating and tranquilizing effects of second-generation antipsychotics (SGAs) in youth.

Methods: As part of the naturalistic inception cohort study, "Second-generation Antipsychotic Treatment Indication, Effectiveness and Tolerability in Youth (SATIETY)," subjective ratings of activating and tranquilizing symptoms were obtained monthly for 3 months from antipsychotic-naïve youth initiating SGAs using the Treatment Emergent Symptoms Scale (TESS). Discontinuation rates, and TESS-reported symptom rates, and severity were related to clinical and treatment parameters. Two compound measures of TESS were defined: presence of any daytime activating (ACTIVATION+) and sedating symptoms (SEDATION+).

Results: In 327 antipsychotic-naïve youth originally initiating the four studied SGAs, discontinuation due to sedation was marginally highest with quetiapine (13.0%) followed by olanzapine (7.3%), risperidone (4.2%), and aripiprazole (2.0%) (p = 0.056). Two hundred fifty-seven antipsychotic-naïve youth (13.8 ± 3.6 years, male = 57.8%) initiated aripiprazole (n = 40), olanzapine (n = 45), quetiapine (n = 36), or risperidone (n = 135) and completed ≥1 postbaseline follow-up visit. Baseline prevalence of ACTIVATION+ (39.9%) or SEDATION+ (54.1%) did not differ between SGAs. Rates of both compound measures changed significantly over time (decrease for ACTIVATION+, p = 0.0002; increase for SEDATION+, p < 0.0001) with slight differences between SGAs, explained by lower rates of ACTIVATION+ with olanzapine (p = 0.002) and slightly higher rates of ACTIVATION+ with aripiprazole (p = 0.018) during follow-up, and lower rates of SEDATION+ with aripiprazole (p = 0.018). All four SGAs reduced insomnia (p = 0.001) and increased hypersomnia (p < 0.001). Postbaseline prevalence of drowsiness, the most frequent, but mild TESS complaint was 85%, without SGA differences. Younger age was associated with activating symptoms, higher age with sedating symptoms, and lower baseline functioning increased both. Psychomotor retardation rates were high in subjects with schizophrenia-spectrum disorders, whereas stimulant comedication was associated with psychomotor activation, regardless of diagnosis.

Conclusions: Although small SGA-specific differences in activating/sedating compound side effect measures were noted, independent predictors of single TESS ratings included clinical parameters, rather than specific SGAs, suggesting a need for carefully individualized treatment strategies.

FIG. 1.

Severity rates of restlessness within the four second-generation antipsychotic treatment groups aripiprazole, quetiapine, olanzapine, and risperidone (left to right) at baseline and week 4, 8, and 12 (left to right). Grey scales indicate symptom severity as subjectively rated on the Treatment Emergent Symptom Scale from mild (light grey), to moderate (dark grey) to severe (black).

FIG. 2.

Severity rates of drowsiness within the four second-generation antipsychotic treatment groups at baseline and week 4, 8 and 12 (left to right). Grey scales indicate symptom severity as subjectively rated on the Treatment Emergent Symptom Scale from mild (light grey), to moderate (dark grey) to severe (black).