Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics A Systematic Review and Meta-analysis


Por: Galling, B, Roldan, A, Nielsen, RE, Nielsen, J, Gerhard, T, Carbon, M, Stubbs, B, Vancampfort, D, De Hert, M, Olfson, M, Kahl, KG, Martin, A, Guo, JJ, Lane, HY, Sung, FC, Liao, CH, Arango, C, Correll, CU

Publicada: 1 mar 2016
Resumen:
IMPORTANCE Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. OBJECTIVE To assess T2DM risk associated with antipsychotic treatment in youth. DATA SOURCES Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. STUDY SELECTION Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. DATA EXTRACTION AND SYNTHESIS Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. MAIN OUTCOMES AND MEASURES The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls RESULTS Thirteen studies were included in the meta-analysis, including 185 105 youth exposed to antipsychotics and 310 438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1 342 121 patients and 2 071 135 patient-years), and 8 studies included healthy controls (298 803 patients and 463 084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls, antipsychotic-exposed youth had significantly higher cumulative T2DM risk (OR, 2.09; 95% CI, 1.50-52.90; P < .0001) and IRR (IRR, 1.79; 95% CI, 1.31-2.44; P < .0001). In multivariable meta-regression analyses of 10 studies, greater cumulative T2DM risk was associated with longer follow-up (P < .001), olanzapine prescription (P < .001), and male sex (P = .002) (r(2) = 1.00, P < .001). Greater T2DM incidence was associated with second-generation antipsychotic prescription (P <= .050) and less autism spectrum disorder diagnosis (P = .048) (r(2) = 0.21, P = .044). CONCLUSIONS AND RELEVANCE Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively.

Filiaciones:
Galling, B:
 North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA

Roldan, A:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed St Pau, Dept Psychiat, E-08193 Barcelona, Spain

Nielsen, RE:
 Aalborg Univ Hosp, Dept Psychiat, Unit Psychiat Res, Aalborg, Denmark

Nielsen, J:
 Aalborg Univ Hosp, Dept Psychiat, Aalborg, Denmark

 Aalborg Univ, Dept Clin Med, Aalborg, Denmark

Gerhard, T:
 Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharm Practice & Adm, Piscataway, NJ USA

 Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA

Carbon, M:
 North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA

Stubbs, B:
 South London & Maudsley Natl Hlth Serv Fdn Trust, Physiotherapy Dept, Denmark Hill, London, England

 Kings Coll London, De Crespigny Pk, London, England

Vancampfort, D:
 Katholieke Univ Leuven, Dept Neurosci, Leuven, Belgium

De Hert, M:
 Katholieke Univ Leuven, Dept Neurosci, Leuven, Belgium

Olfson, M:
 Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY USA

Kahl, KG:
 Hannover Med Sch, Dept Psychiat Social Psychiat & Psychotherapy, Hannover, Germany

Martin, A:
 Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA

Guo, JJ:
 Univ Cincinnati, Med Ctr, Coll Pharm, Cincinnati, OH 45267 USA

Lane, HY:
 China Med Univ, Inst Clin Med Sci, Taichung, Taiwan

 China Med Univ, Dept Psychiat, Taichung, Taiwan

Sung, FC:
 China Med Univ, Dept Publ Hlth, Taichung, Taiwan

Liao, CH:
 China Med Univ, Dept Psychiat, Taichung, Taiwan

 China Med Univ, Dept Publ Hlth, Taichung, Taiwan

Arango, C:
 Univ Complutense Madrid, Inst Invest Sanitaria Gregorio Maranon, Child & Adolescent Psychiat Dept, Hosp Gen Univ Gregorio Maranon,Sch Med,CIBERSAM, Madrid, Spain

Correll, CU:
 North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA

 Hofstra North Shore Long Isl Jewish Sch Med, Hempstead, NY USA

 Feinstein Inst Med Res, Manhasset, NY USA
ISSN: 2168622X





JAMA Psychiatry
Editorial
AMER MEDICAL ASSOC, 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA, Estados Unidos America
Tipo de documento: Review
Volumen: 73 Número: 3
Páginas: 247-259
WOS Id: 000371613500012
ID de PubMed: 26792761
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