Activating and Tranquilizing Effects of First-Time Treatment with Aripiprazole, Olanzapine, Quetiapine, and Risperidone in Youth.
To assess activating and tranquilizing effects of second-generation antipsychotics (SGAs) in youth.



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+).



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.



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.
1 Department of Psychiatry, New York University Langone Medical Center , New York, New York.
Zainab
Z
Al-Dhaher
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.
Sandeep
S
Kapoor
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.|3 Department of Psychiatry, Hofstra North Shore LIJ School of Medicine , Hempstead, New York.|4 Department of Molecular Medicine, Hofstra North Shore LIJ School of Medicine , Hempstead, New York.
Ema
E
Saito
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.
Scott
S
Krakower
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.
Lisa
L
David
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.
Theodore
T
Ake
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.|3 Department of Psychiatry, Hofstra North Shore LIJ School of Medicine , Hempstead, New York.|4 Department of Molecular Medicine, Hofstra North Shore LIJ School of Medicine , Hempstead, New York.|5 Center for Psychiatric Neuroscience , The Feinstein Institute for Medical Research, Manhasset, New York.
John M
JM
Kane
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.|3 Department of Psychiatry, Hofstra North Shore LIJ School of Medicine , Hempstead, New York.|4 Department of Molecular Medicine, Hofstra North Shore LIJ School of Medicine , Hempstead, New York.|5 Center for Psychiatric Neuroscience , The Feinstein Institute for Medical Research, Manhasset, New York.
Christoph U
CU
Correll
2 Division of Psychiatry Research, The Zucker Hillside Hospital , North Shore-Long Island Jewish Health System, Glen Oaks, New York.
Maren
M
Carbon
D000293:Adolescent; D000068180:Aripiprazole / Q000009:adverse effects* / Q000627:therapeutic use*; D001143:Arousal / Q000187:drug effects*; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D063868:Patient Outcome Assessment; D011595:Psychomotor Agitation / Q000175:diagnosis* / Q000523:psychology; D000069348:Quetiapine Fumarate / Q000009:adverse effects* / Q000627:therapeutic use*; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use*; D012561:Schizophrenia, Childhood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D014851:Wakefulness / Q000187:drug effects*
D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D018967:Risperidone; D000077152:Olanzapine