Post hoc analyses of asenapine treatment in pediatric patients with bipolar I disorder: efficacy related to mixed or manic episode, stage of illness, and body weight

Abstract

Background

Patient characteristics and disease progression may affect response to pharmacologic intervention in bipolar I disorder. Asenapine is approved for acute treatment of manic/mixed episodes of bipolar I disorder in patients 10–17 years old. Post hoc analyses assessed asenapine efficacy in pediatric patients by current manic or mixed episode, number of lifetime episodes, and baseline body mass index (BMI).

Patients and methods

Data were obtained from a 3-week, randomized, double-blind, placebo-controlled, parallel-group trial of asenapine 2.5, 5.0, or 10.0 mg twice daily (BID) in male or female patients (10–17 years) with bipolar I disorder (NCT01244815). Patients were stratified by current episode type (Diagnostic and Statistical Manual of Mental Disorders, fourth edition – defined mixed/manic), number of lifetime episodes (<3, 3–5, >5), and baseline BMI tertile. Changes from baseline to day 21 in Young Mania Rating Scale (YMRS) total score and Clinical Global Impressions Scale for use in Bipolar Illness (CGI-BP) were assessed in asenapine subgroups vs placebo.

Results

In patients with mixed episodes, differences in YMRS and CGI-BP scores were statistically significant for each asenapine dose vs placebo (P<0.001) at day 21; in patients with manic episodes, significant differences vs placebo were seen in all groups (P<0.05) except 2.5 mg BID on the YMRS. In patients with <3 previous mixed/manic episodes, significant differences in YMRS and CGI-BP scores were observed for all asenapine doses vs placebo (P<0.05). In patients with 3–5 or >5 previous episodes, asenapine 10 mg BID was significantly different than placebo (P<0.05) on both scales; differences vs placebo varied for lower doses. Baseline body weight or BMI did not appear to influence the efficacy of asenapine.

Conclusion

Asenapine was effective in the treatment of pediatric patients with bipolar I disorder. Efficacy did not appear to be influenced by the type of current episode, stage of disease progression, or baseline body weight/BMI.

Keywords:

• asenapine
• child
• adolescent
• bipolar disorder
• atypical antipsychotic
• second-generation antipsychotic

Supplementary material

List of independent ethics committees

1. Schulman Associates Institutional Review Board, Inc. 4445 Lake Forest Dr, Suite 300, Cincinnati, OH 45242, USA

2. Western Institutional Review Board, 3535 7th Ave SW, Olympia, WA 98502, USA

3. Chesapeake Research Review, Inc. 7063 Columbia Gateway Dr, Suite 110, Columbia, MD 21046, USA

4. Stanford Human Research Protection Program, 1501 S. California Ave. Research Compliance Office, Palo Alto, CA 94304-5579, USA

5. Office of Institutional Review (UHCMC IRB), University Hospitals Case Medical Center, 11100 Euclid Avenue, Lakeside 1400, Cleveland, OH 44106, USA

6. UCSF Committee on Human Research, 3333 California St., Suite 315, Office of Research, San Francisco, CA 94118, USA

7. St. Anthony IRB, 1000 N. Lee St. Oklahoma City, OK 73101, USA

8. Hartford Hospital Cardiac Lab, 80 Seymour St. Hartford, CT 06102, USA

9. Sharp Healthcare Institutional Review Board, 8695 Spectrum Center Blvd, San Diego, CA 92123, USA

10. New York State Psychiatric IRB, 1051 Riverside Drive, Suite 5200, New PI building, New York, NY 10032, USA

11. Via Christi Medical Center, 929 N. St. Francis, Institutional Review Board, Wichita, KS 67214, USA

12. Howard University IRB, 1840 NW 7th St., Suite 309, Washington, DC 20001, USA

13. Integris Health IRB, 3330 NW 56th St., Suite 310, Oklahoma City, OK 73112, USA

14. North Shore LIJ Institute of Medical Research, 350 Community Drive, Manhasset, NY 11030, USA

15. Kootenai Health IRB, 2003 Koonetai Health Way, Coeur d’Alene, ID 83814, USA

16. Office of Research Integrity, 19 Hagood Ave. – Room 601, Harborview Office Tower, Charleston, SC 29425, USA

17. Office of Research Integrity, Box 800483, University of Virginia IRB, Charlottesville, VA 22908, USA

18. University of Texas Health Science Center at Houston, 6410 Fannin, Suite 1100 IRB, Committee for the Protection of Human Subjects, Houston, TX 77030, USA

19. Partners Human Research Committee, 116 Huntington Ave., Suite 1002, Partners Human Research Office, Boston, MA 02116, USA

20. Saratov City Clinical Hospital #2 n.a. V.I. Razumovsky, Chernyshevskogo St. 141, Department of Psychiatry, Saratov 410028, Russia

21. EC at Sverdlovsky Regional Clinical Psychiatry Hospital, 8th km, ulitsa Sibirsky trakt, Ekaterinburg 620030, Russia

22. IEC at St. Petersburg Research Psychoneurology Institute, 3 Bekhtereva St. Saint Petersburg 192019, Russia

23. Research-And-Educational Centre of Psychotherapy, Lenina St. 417, build. 3, Stavropol 355000, Russia

24. IIEC on Ethical Review for Clinical Studies, Leningradsky prospekt, 51, Moscow 125468, Russia

25. Stavropol Region Psychiatric Hospital #2, 84 Koroleva Street, Kochubeev district Stavropol region, Township Tonnelniy 357034, Russia

26. LEC at Central Clinical Psychiatric Hospital, 1, 8 Marta ul. Moscow 127083, Russia

27. Russian State Medical University, Faculty of Psychiatry, 3 Poteshnaya street, Moscow 107076, Russia

Acknowledgments

Writing assistance and editorial support were provided by Krystina Neuman, PhD, of Prescott Medical Communications Group (Chicago, IL), a contractor of Allergan. The study was sponsored by Merck & Co., Inc. This manuscript was supported by funding from Allergan (Madison, NJ).

Author contributions

Robert L Findling, Willie Earley, Trisha Suppes, Mehul Patel, and Roger S McIntyre contributed to the concept/design of these analyses and data analyses/interpretation. Xiao Wu and Cheng-Tao Chang were involved in the statistical analysis and interpretation of data. All authors contributed toward data analyses/interpretation, drafting and critically revising the paper, and they agree to be responsible for all aspects of the work.

Disclosure

Dr Findling receives or has received research support, acted as a consultant and/or served on a speaker’s bureau for Aevi, Akili, Alcobra, Amerex, American Academy of Child & Adolescent Psychiatry, American Psychiatric Press, Bracket, Epharma Solutions, Forest, Genentech, Guilford Press, Ironshore, Johns Hopkins University Press, KemPharm, Lundbeck, Merck, NIH, Neurim, Nuvelution, Otsuka, PCORI, Pfizer, Physicians Postgraduate Press, Purdue, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, Syneurx, Teva, Tris, TouchPoint, Validus, and WebMD.

Dr Suppes has reported grants from National Institute of Mental Health, VA Cooperative Studies Program, Pathway Genomics, Stanley Medical Research Institute, Elan Pharma International Limited, and Sunovion Pharmaceuticals; consulting fees from A/S H. Lundbeck, Sunovion, Merck & Co., and Astra Zeneca; honoraria from Medscape Education, Global Medical Education, and CMEology; royalties from Jones and Bartlett and UpToDate.

Dr McIntyre has received research grant support from Lundbeck, AstraZeneca, Pfizer, Shire, Otsuka, Bristol-Myers Squibb, National Institute of Mental Health, Stanley Medical Research Institute, Canadian Institutes for Health Research, and The Brain and Behavior Research Foundation. He has also received speaker/consultant fees from Lundbeck, Pfizer, AstraZeneca, Eli Lilly, Janssen Ortho, Sunovion, Takeda, Forest, Otsuka, Bristol-Myers Squibb, and Shire.

Drs Earley and Patel acknowledge potential conflicts of interest as employees of Allergan.

Drs Wu and Chang acknowledge potential conflicts of interest as former employees of Allergan.

The authors report no other conflicts of interest in this work.