Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: A pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies

International Clinical Psychopharmacology

Volumn 32, Issue 6, 2017, Pages 319-328

  Earley, Willie ^a   Durgam, Suresh ^a   Lu, Kaifeng ^a   Laszlovszky, István ^c   Debelle, Marc ^c   Kane, John M ^b  

^a Allergan plc   (United States)

^b ZUCKER HILLSIDE HOSPITAL   (United States)

^c GEDEON RICHTER LTD   (Hungary)

Author keywords

antipsychotic; cariprazine; post hoc analysis; safety and tolerability; schizophrenia

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; CARIPRAZINE; CREATINE KINASE; PLACEBO; PROLACTIN; DOPAMINE RECEPTOR STIMULATING AGENT; NEUROLEPTIC AGENT; PIPERAZINE DERIVATIVE;

ABDOMINAL PAIN; ADULT; AGED; AKATHISIA; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ANXIETY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BLURRED VISION; BODY WEIGHT; CONSTIPATION; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DIASTOLIC BLOOD PRESSURE; DISEASE EXACERBATION; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EXTRAPYRAMIDAL SYMPTOM; FEMALE; HEADACHE; HUMAN; HYPERTENSION; INSOMNIA; MAJOR CLINICAL STUDY; MALE; METABOLIC PARAMETERS; NAUSEA; ORTHOSTATIC HYPOTENSION; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROLACTIN BLOOD LEVEL; PSYCHOSIS; QTC INTERVAL; RANDOMIZED CONTROLLED TRIAL; RESTLESSNESS; SCHIZOPHRENIA; SIDE EFFECT; SOMNOLENCE; STATISTICAL ANALYSIS; SUICIDAL BEHAVIOR; SUICIDAL IDEATION; TOOTH PAIN; VOMITING; WEIGHT GAIN; ACUTE DISEASE; CHEMICALLY INDUCED; EXTRAPYRAMIDAL SYNDROME; META ANALYSIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROCEDURES; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT OUTCOME;

ACUTE DISEASE; ANTIPSYCHOTIC AGENTS; BASAL GANGLIA DISEASES; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DOPAMINE AGONISTS; DOUBLE-BLIND METHOD; HEADACHE; HUMANS; PIPERAZINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SCHIZOPHRENIA; TREATMENT OUTCOME;

EID: 85022187263     PISSN: 02681315     EISSN: 14735857     Source Type: Journal    
DOI: 10.1097/YIC.0000000000000187     Document Type: Article

References (44)

1. Abilify, 2014, Prescribing information; Princeton, NJ. Rockville, MD: Otsuka America Pharmaceuticals Inc
2. American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. Washington, DC: American Psychiatric Association.
3. Barnes TR (1989). A rating scale for drug-induced akathisia. Br J Psychiatry 154:672-676.
4. Caroff SN, Mann SC, Campbell EC, Sullivan KA (2002). Movement disorders associated with atypical antipsychotic drugs. J Clin Psychiatry 63 (Suppl 4): 12-19.
5. Cha DS, Mcintyre RS (2012). Treatment-emergent adverse events associated with atypical antipsychotics. Expert Opin Pharmacother 13:1587-1598.
6. Durgam S, Starace A, Li D, Migliore R, Ruth A, Nemeth G, et al. (2014). An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: A phase II, randomized clinical trial. Schizophr Res 152:450-457.
7. Durgam S, Cutler AJ, Lu K, Migliore R, Ruth A, Laszlovszky I, et al. (2015). Cariprazine in acute exacerbation of schizophrenia: A fixed-dose, phase 3, randomized, double-blind, placebo-And active-controlled trial. J Clin Psychiatry 76:e1574-e1582.
8. Durgam S, Litman RE, Papadakis K, Li D, Nemeth G, Laszlovszky I (2016). Cariprazine in the treatment of schizophrenia: A proof-of-concept trial. Int Clin Psychopharmacol 31:61-68.
9. Farah A (2005). Atypicality of atypical antipsychotics. Prim Care Companion J Clin Psychiatry 7:268-274.
10. Girgis RR, Slifstein M, D'Souza D, Lee Y, Periclou A, Ghahramani P, et al. (2016). Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-( +)-PHNO. Psychopharmacology (Berl) 233:3503-3512.
11. Goff DC, Cather C, Evins AE, Henderson DC, Freudenreich O, Copeland PM, et al. (2005). Medical morbidity and mortality in schizophrenia: guidelines for psychiatrists. J Clin Psychiatry 66:183-194.
12. GuyW(1976a). The Abnormal Movement Scale, ECDEU assessment manual for psychopharmacology. Rockville, MD: National Institutes of Mental Health. pp. 218-222.
13. Guy W (1976b). Clinical global impressions. In: Guy W, editor. ECDEU assessment manual for psychopharmacology: publication ADM. Rockville, MD: National Institute of Mental Health, Psychopharmacology Research Branch. pp. 76-338.
14. Gyertyan I, Saghy K, Laszy J, Elekes O, Kedves R, Gemesi LI, et al. (2008). Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: II. behavioural characterisation of RG-15. Naunyn Schmiedebergs Arch Pharmacol 378:529-539.
15. Gyertyan I, Kiss B, Saghy K, Laszy J, Szabo G, Szabados T, et al. (2011). Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents. Neurochem Int 59:925-935.
16. Henderson DC, Doraiswamy PM (2008). Prolactin-related and metabolic adverse effects of atypical antipsychotic agents. J Clin Psychiatry 69 (Suppl 1): 32-44.
17. Hennekens CH (2007). Increasing global burden of cardiovascular disease in general populations and patients with schizophrenia. J Clin Psychiatry 68 (Suppl 4):4-7.
18. Kane JM, Sharif ZA (2008). Atypical antipsychotics: sedation versus efficacy. J Clin Psychiatry 69 (Suppl 1):18-31.
19. Kane JM, Fleischhacker WW, Hansen L, Perlis R, Pikalov A 3rd, Assuncao-Talbott S (2009). Akathisia: An updated review focusing on secondgeneration antipsychotics. J Clin Psychiatry 70:627-643.
20. Kane JM, Barnes TR, Correll CU, Sachs G, Buckley P, Eudicone J, et al. (2010). Evaluation of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder: A post hoc analysis of pooled data from short-And longterm aripiprazole trials. J Psychopharmacol 24:1019-1029.
21. Kane JM, Zukin S, Wang Y, Lu K, Ruth A, Nagy K, et al. (2015). Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: results from an international, phase III clinical trial. J Clin Psychopharmacol 35:367-373.
22. Kay SR, Fiszbein A, Opler LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261-276.
23. Kiss B, Laszlovszky I, Horvath A, Nemethy Z, Schmidt E, Bugovics G, et al. (2008). Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15. Naunyn Schmiedebergs Arch Pharmacol 378:515-528.
24. Kiss B, Horvath A, Nemethy Z, Schmidt E, Laszlovszky I, Bugovics G, et al. (2010). Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther 333:328-340.
25. Kreyenbuhl J, Buchanan RW, Dickerson FB, Dixon LB (2010). The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull 36:94-103.
26. Kumar R, Sachdev PS (2009). Akathisia and second-generation antipsychotic drugs. Curr Opin Psychiatry 22:293-299.
27. Laszy J, Laszlovszky I, Gyertyan I (2005). Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats. Psychopharmacology (Berl) 179:567-575.
28. Latuda (2013). Prescribing information. Marlborough, MA: Sunovion Pharmaceuticals Inc
29. Lehman AF, Lieberman JA, Dixon LB, Mcglashan TH, Miller AL, Perkins DO, et al. (2004). Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 161:1-56.
30. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM (2009). Secondgeneration versus first-generation antipsychotic drugs for schizophrenia: A meta-Analysis. Lancet 373:31-41.
31. Miller DD, Caroff SN, Davis SM, Rosenheck RA, Mcevoy JP, Saltz BL, et al. (2008). Extrapyramidal side-effects of antipsychotics in a randomised trial. Br J Psychiatry 193:279-288.
32. Miyamoto S, Duncan GE, Marx CE, Lieberman JA (2005). Treatments for schizophrenia: A critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10:79-104.
33. Newcomer JW (2007). Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry 68 (Suppl 4):8-13.
34. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. (2011). The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 168:1266-1277.
35. Poyurovsky M (2010). Acute antipsychotic-induced akathisia revisited. Br J Psychiatry 196:89-91.
36. Riordan HJ, Antonini P, Murphy MF (2011). Atypical antipsychotics and metabolic syndrome in patients with schizophrenia: risk factors, monitoring, and healthcare implications. Am Health Drug Benefits 4:292-302.
37. Risperdal (2014). Prescribing information. Titusville, NJ: Janssen LP.
38. Saha S, Chant D, Mcgrath J (2007). A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 64:1123-1131.
39. Saphris, 2014, Prescribing information. St Louis, MO: Forest Pharmaceuticals Inc
40. Schwartz JC, Diaz J, Pilon C, Sokoloff P (2000). Possible implications of the dopamine D(3) receptor in schizophrenia and in antipsychotic drug actions. Brain Res Brain Res Rev 31:277-287.
41. Simpson GM, Angus JW (1970). A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 212:11-19.
42. Stanniland C, Taylor D (2000). Tolerability of atypical antipsychotics. Drug Saf 22:195-214.
43. Tandon R (2002). Safety and tolerability: how do newer generation "atypical" antipsychotics compare? Psychiatr Q 73:297-311.
44. Zyprexa, 2011, Prescribing information. Indianapolis, IN: Eli Lily and Company