Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: A systematic review and exploratory meta-analysis

CNS Drugs

Volumn 26, Issue 9, 2012, Pages 733-759

  De Hert, Marc ^a   Yu, Weiping ^a   Detraux, Johan ^a   Sweers, Kim ^a   Van Winkel, Ruud ^a,b   Correll, Christoph U ^c,d,e,f  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^c ZUCKER HILLSIDE HOSPITAL   (United States)

^d ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^e FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH   (United States)

^f DONALD AND BARBARA ZUCKER SCHOOL OF MEDICINE AT HOFSTRA NORTHWELL   (United States)

Author keywords

Antipsychotics Asenapine; Bipolar disorders; Cholesterol; Glucose; Iloperidone; Lurasidone; Meta analysis; Paliperidone; Schizophrenia; Triglycerides

Indexed keywords

ASENAPINE; CHOLESTEROL; GLUCOSE; ILOPERIDONE; LURASIDONE; PALIPERIDONE; TRIACYLGLYCEROL;

BIPOLAR DISORDER; BODY WEIGHT; CHOLESTEROL BILE LEVEL; CINAHL; CLINICAL DECISION MAKING; CONFIDENCE INTERVAL; EMBASE; GLUCOSE BLOOD LEVEL; HUMAN; INFORMATION RETRIEVAL; LIPID METABOLISM; MEDLINE; META ANALYSIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCHIZOPHRENIA; SIDE EFFECT; SYSTEMATIC REVIEW; TRIACYLGLYCEROL BLOOD LEVEL; WEIGHT GAIN;

ANTIPSYCHOTIC AGENTS; BIPOLAR DISORDER; BLOOD GLUCOSE; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; ISOINDOLES; ISOXAZOLES; LIPID METABOLISM; PIPERIDINES; PYRIMIDINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SCHIZOPHRENIA; THIAZOLES; WEIGHT GAIN;

EID: 84865253275     PISSN: 11727047     EISSN: 11791934     Source Type: Journal    
DOI: 10.2165/11634500-000000000-00000     Document Type: Review

References (90)

1. McDonagh M, Peterson K, Carson S, et al. Drug class re-view: atypical antipsychotic drugs: final update 3 report. Portland (OR): Oregon Health & Science University, 2010 Jul
2. Kane JM, Correll CU. Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry 2010 Sep; 79 (9): 1115-24
3. De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with anti-psychotic drugs. Nat Rev Endocrinol 2012; 8: 114-26
4. De Hert M, Dobbelaere M, Sheridan EM, et al. Metabolic and endocrine adverse effects of second-generation anti-psychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry 2011 Apr; 26 (3): 144-58
5. Maayan L, Vakhrusheva J, Correll CU. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology 2010 Jun; 35 (7): 1520-30
6. Correll CU, Lencz T, Malhotra AK. Antipsychotic drugs and obesity. Trends Mol Med 2011 Feb; 17 (2): 97-107
7. De Hert M, Correll CU, Bobes J, et al. Physical illness in patients with severe mental disorders: I. Prevalence, impact of medications and disparities in health care. World Psychiatry 2011 Feb; 10 (1): 52-77
8. Leucht S, Corves C, Arbter D, et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009 Jan 3; 373 (9657): 31-41
9. Rummel-Kluge C, Komossa K, Schwarz S, et al. Second-generation antipsychotic drugs and extrapyramidal side effects: a systematic review and meta-analysis of head-to-head comparisons. Schizophr Bull 2012 Jan; 38 (1): 167-77
10. Parsons B, Allison DB, Loebel A, et al. Weight effects associated with antipsychotics: a comprehensive database analysis. Schizophr Res 2009 May; 110 (1-3): 103-10
11. Coccurello R, Moles A. Potential mechanisms of atypical antipsychotic-induced metabolic derangement: clues for understanding obesity and novel drug design. Pharmacol Ther 2010 Sep; 127 (3): 210-51
12. Kahn RS, Fleischhacker WW, Boter H, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008 Mar 29; 371 (9618): 1085-97
13. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 2005; 19 Suppl. 1: 1-93
14. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005 Sep 22; 353 (12): 1209-23
15. Citrome L. Risk-benefit analysis of available treatments for schizophrenia. Psychiatric Times 2007; 1: 27-30
16. Tarricone I, Ferrari Gozzi B, Serretti A, et al. Weight gain in antipsychotic-naive patients: a review and meta-analysis. Psychol Med 2010 Feb; 40 (2): 187-200
17. Alvarez-Jimenez M, Gonzalez-Blanch C, Crespo-Facorro B, et al. Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematic critical reappraisal. CNS Drugs 2008; 22 (7): 547-62
18. Strassnig M, Miewald J, Keshavan M, et al. Weight gain in newly diagnosed first-episode psychosis patients and healthy comparisons: one-year analysis. Schizophr Res 2007 Jul; 93 (1-3): 90-8
19. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009 Oct 28; 302 (16): 1765-73
20. Reynolds GP, Kirk SL. Metabolic side effects of anti-psychotic drug treatment: pharmacological mechanisms. Pharmacol Ther 2010 Jan; 125 (1): 169-79
21. Pringsheim T, Lam D, Ching H, et al. Metabolic and neurological complications of second-generation anti-psychotic use in children: a systematic review and meta-analysis of randomized controlled trials. Drug Saf 2011; 34 (8): 651-68
22. Rummel-Kluge C, Komossa K, Schwarz S, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 2010 Nov; 123 (2-3): 225-33
23. Meyer JM, Davis VG, McEvoy JP, et al. Impact of anti-psychotic treatment on nonfasting triglycerides in the CA-TIE Schizophrenia Trial phase 1. Schizophr Res 2008 Aug; 103 (1-3): 104-9
24. Sikich L, Frazier JA, McClellan J, et al. Double-blind comparison of first-and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry 2008 Nov; 165 (11): 1420-31
25. Nielsen J, Skadhede S, Correll CU. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naive schizophrenia patients. Neuropsychopharmacology 2010 Aug; 35 (9): 1997-2004
26. Citrome L. Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics. Postgrad Med 2011 Mar; 123 (2): 153-62
27. Howland RH. Update on newer antipsychotic drugs. J Psychosoc Nurs Ment Health Serv 2011 Apr; 49 (4): 13-5
28. Meltzer HY, Bobo WV, Nuamah IF, et al. Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6-week, placebo-controlled studies. J Clin Psychiatry 2008 May; 69 (5): 817-29
29. Marder SR, Kramer M, Ford L, et al. Efficacy and safety of paliperidone extended-release tablets: results of a 6-week, randomized, placebo-controlled study. Biol Psychiatry 2007 Dec 15; 62 (12): 1363-70
30. Olivo SA, Macedo LG, Gadotti IC, et al. Scales to assess the quality of randomized controlled trials: a systematic review. Phys Ther 2008 Feb; 88 (2): 156-75
31. Hayashino Y, Noguchi Y, Fukui T. Systematic evaluation and comparison of statistical tests for publication bias. J Epidemiol 2005 Nov; 15 (6): 235-43
32. Calabrese JR, Stet L, Kothari H, et al. Asenapine as adjunctive treatment for bipolar mania: results of a placebo-controlled 12-week study and 40-week extension. American Psychiatric Association's 62nd Institute on Psychiatric Services; 2010 Oct 14-17; Boston (MA)
33. Kane JM, Cohen M, Zhao J, et al. Efficacy and safety of asenapine in a placebo-and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia. J Clin Psychopharmacol 2010 Apr; 30 (2): 106-15
34. McIntyre RS, Cohen M, Zhao J, et al. Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial. J Affect Disord 2010 Apr; 122 (1-2): 27-38
35. McIntyre RS, Cohen M, Zhao J, et al. A 3-week, random-ized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states. Bipolar Disord 2009 Nov; 11 (7): 673-86
36. Potkin SG, Cohen M, Panagides J. Efficacy and tolerability of asenapine in acute schizophrenia: a placebo-and ris-peridone-controlled trial. J Clin Psychiatry 2007 Oct; 68 (10): 1492-500
37. Kane JM, Mackle M, Snow-Adami L, et al. A randomized placebo-controlled trial of asenapine for the prevention of relapse of schizophrenia after long-term treatment. J Clin Psychiatry 2011; 72 (3): 349-55
38. McIntyre RS, Cohen M, Zhao J, et al. Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study. J Affect Disord Nov 2010; 126 (3): 358-65
39. Schoemaker J, Naber D, Vrijland P, et al. Long-term as-sessment of asenapine vs. olanzapine in patients with schizophrenia or schizoaffective disorder. Pharmacopsychiatry 2010; 43 (4): 138-46
40. Cutler AJ, Kalali AH, Weiden PJ, et al. Four-week, double-blind, placebo-and ziprasidone-controlled trial of iloperidone in patients with acute acute exacerbations of schizophrenia. J Clin Psychopharmacol 2008 Apr; 28 (2 Suppl. 1): S20-8
41. FDA. Drug approval package: Fanapt® (iloperidone) tablets, 27 July 2008 [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda- docs/nda/2009/022192s 000-MedR-P1.pdf [Accessed 2012 Feb 6]
42. Kane JM, Lauriello J, Laska E, et al. Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia. J Clin Psychopharmacol 2008 Apr; 28 (2 Suppl. 1): S29-35
43. Nasrallah HA, Weiden P, Citrome L, et al. The metabolic profile of iloperidone compared to ziprasidone in a short-term, placebo-controlled clinical trial and 25-week, a open-label extension. American College of Neuropyscho-pharmacology; 2010 Dec 5-9; Miami Beach (FL)
44. Potkin S, Ogasa M, Cucchiaro J, et al. Double-blind com-parison of the safety and efficacy of lurasidone and ziprasidone in clinically stable outpatients with schizophrenia or schizoaffective disorder. Schizophr Res 2011; 132 (2-3): 101-7
45. FDA. Drug approval package: Latuda® (lurasidone hydro-chloride) tablets, 3 December 2010 [online]. Available from URL: http://www.accessdata. fda.gov/drugsatfda-docs/nda/2010/200603Orig1s000MedR.pdf [Accessed 2012 Feb 6]
46. Loebel A, Cucchiaro J, Sarma K, et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled study (PEARL 3). American College of Neuro-psychopharmacology; 2010 Dec 5-9; Miami Beach (FL)
47. Citrome L, Cucchiaro J, Sarma K, et al. Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month, double-blind, active-controlled study. Int Clin Psychopharmacol 2012 May; 27 (3): 165-76
48. Berwaerts J, Lane R, Nuamah IF, et al. Paliperidone extended-release as adjunctive therapy to lithium or valproate in the treatment of acute mania: a randomized, placebo-controlled study. J Affect Disord 2011; 129: 252-60
49. Invega® (paliperidone) extended-release tablets [package insert]. Titusville (NJ): Ortho-McNeil Neurologics, Inc., 2007 Apr
50. Singh J, Robb A, Vijapurkar U, et al. A randomized, dou-ble-blind study of paliperidone extended-release in treatment of acute schizophrenia in adolescents. Biol Psychiatry 2011; 70: 1179-87
51. Canuso CM, Lindenmayer JP, Kosik-Gonzalez C, et al. A randomized, double-blind, placebo-controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with schizoaffective disorder. J Clin Psychiatry 2010 May; 71 (5): 587-98
52. Hough D, Gopal S, Vijapurkar U, et al. Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res 2010 Feb; 116 (2-3): 107-17
53. Vieta E, Nuamah IF, Lim P, et al. A randomized, placebo-and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 2010; 12: 230-43
54. Canuso CM, Dirks B, Carothers J, et al. Randomized, double-blind, placebo-controlled study of paliperidone extended-release and quetiapine in inpatients with recently exacerbated schizophrenia. Am J Psychiatry 2009 Jun; 166 (6): 691-701
55. Schreiner A, Badescu GM, Jukic V, et al. Safety, tolerability and treatment response of flexible doses of paliperidone ER in acutely exacerbated patients with schizophrenia (Pertain) [poster]. World Psychiatry Association; 2009 Apr 1-4; Florence
56. Tzimos A, Samokhvalov V, Kramer M, et al. Safety and tolerability of oral paliperidone extended-release tablets in elderly patients with schizophrenia: a double-blind, placebo-controlled study with six-month open-label extension. Am J Geriatr Psychiatry 2008 Jan; 16 (1): 31-43
57. Davidson M, Emsley R, Kramer M, et al. Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomized, placebo-controlled study. Schizophr Res 2007; 93 (1-3): 117-30
58. Kane J, Canas F, Kramer M, et al. Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial. Schizophr Res 2007 Feb; 90 (1-3): 147-61
59. Gopal S, Vijapurkar U, Lim P, et al. A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia. J Psychopharmacol 2011 May; 25 (5): 685-97
60. Alphs L, Bossie CA, Sliwa JK, et al. Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial. Ann Gen Psychiatry 2011; 10 (12): 1-10
61. Everitt J, Rey JA. Medication use evaluation: metabolic side effects of paliperidone in an inpatient psychiatric facility. 13th Annual Meeting of the College of Psychiatric and Neurologic Pharmacists; 2010 Apr 18-21; San Antonio (TX)
62. Li H, Rui Q, Ning X. A comparative randomized, open-label, rater-blinded study of paliperidone palmitate and risperidone long acting injectable therapy in patients with schizophrenia. Poster presented at the 27th International College of Neuropsychopharmacology Congress; 2010 Jun 6-10; Hong Kong
63. Nasrallah HA, Gopal S, Gassmann-Mayer C, et al. A con-trolled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia. Neuropsychopharmacology 2010 Sep; 35 (10): 2072-82
64. Pandina GJ, Lindenmayer JP, Lull J, et al. A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol 2010 Jun; 30 (3): 235-44
65. Schreiner A, Tessier C, Hoeben D, et al. A flexible-dose study of paliperidone ER in non-acute patients with schizophrenia previously unsuccessfully treated with other oral antipsychotics [poster]. 18th European Congress of Psychiatry; 2010 Feb 27-Mar 2; Munich
66. Emsley R, Berwaerts J, Eerderkens M, et al. Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies. Int Clin Psychopharm 2008; 23 (6): 343-56
67. Kramer M, Simpson G, Maciulis V. Oral paliperidone ex-tended-release treatment: long-term metabolic outcomes in patients with schizophrenia [poster]. WWS; 2008 Feb 3-7; Montreux
68. Kramer M, Simpson G, Maciulis V, et al. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, doubleblind, placebo-controlled study. J Clin Psychopharmacol 2007 Feb; 27 (1): 6-14
69. Citrome L. Asenapine for schizophrenia and bipolar dis-order: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. Int J Clin Pract 2009 Dec; 63 (12): 1762-84
70. Weber J, McCormack PL. Asenapine. CNS Drugs 2009 Sep 1; 23 (9): 781-92
71. Emsley RA, Schoemaker JH, Vrijland P, et al. Long-term safety of asenapine versus olanzapine in patients with schizophrenia or schizoaffective disorder [abstract no. 323]. 21st Annual US Psychiatric and Mental Health Congress; 2008 Oct 30-Nov 1; San Diego (CA)
72. Citrome L, Nasrallah HA. On-label on the table: what the package insert informs us about the tolerability profile of oral atypical antipsychotics, and what it does not. Expert Opin Pharmacother 2012 Aug; 13 (11): 1599-613
73. Kroeze WK, Hufeisen SJ, Popadak BA, et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharma-cology 2003 Mar; 28 (3): 519-26
74. Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review. J Clin Psychiatry 2009 Jul; 70 (7): 1041-50
75. Kim SF, Huang AS, Snowman AM, et al. From the cover: antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proc Natl Acad Sci U S A 2007 Feb 27; 104 (9): 3456-9
76. Meltzer HY, Massey BW. The role of serotonin receptors in the action of atypical antipsychotic drugs. Curr Opin Pharmacol 2011 Feb; 11 (1): 59-67
77. Citrome L. Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic. Int J Clin Pract 2011 Feb; 65 (2): 189-210
78. Thompson A, Lavedan C, Volpi S. Absence of weight gain association with the HTR2C-759C/T polymorphism in patients with schizophrenia treated with iloperidone. Psychiatry Res 2010 Feb 28; 175 (3): 271-3
79. Bishara D, Taylor D. Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and toler-ability. Drugs 2008; 68 (16): 2269-92
80. Reynolds GP, Zhang Z, Zhang X. Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain. Am J Psychiatry 2003 Apr; 160 (4): 677-9
81. Miller DD, Ellingrod VL, Holman TL, et al. Clozapine-induced weight gain associated with the 5HT2C receptor-759C/T polymorphism. Am J Med Genet B Neuropsychiatr Genet 2005 Feb 5; 133B (1): 97-100
82. Ellingrod VL, Perry PJ, Ringold JC, et al. Weight gain associated with the-759C/T polymorphism of the 5HT2C receptor and olanzapine. Am J Med Genet B Neuro-psychiatr Genet 2005 Apr 5; 134B (1): 76-8
83. Reynolds GP, Zhang ZJ, Zhang XB. Association of anti-psychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 2002 Jun 15; 359 (9323): 2086-7
84. Templeman LA, Reynolds GP, Arranz B, et al. Poly-morphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Phar-macogenet Genomics 2005 Apr; 15 (4): 195-200
85. Johnson DE, Nedza FM, Spracklin DK, et al. The role of muscarinic receptor antagonism in antipsychotic-induced hippocampal acetylcholine release. Eur J Pharmacol 2005 Jan 4; 506 (3): 209-19
86. Silvestre JS, Prous J. Research on adverse drug events: I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes. Methods Find Exp Clin Pharmacol 2005 Jun; 27 (5): 289-304
87. Citrome L. Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion. Expert Opin Drug Metab Toxicol 2010; 6 (12): 1551-64
88. Bishara D, Taylor D. Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder. Neuropsychiatr Dis Treat 2009; 5: 483-90
89. Bishara D. Once-monthly paliperidone injection for the treatment of schizophrenia. Neuropsychiatr Dis Treat 2010 Sep 7; 6: 561-72
90. Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 2008 Jan; 13 (1): 27-35