Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study

Psychopharmacology

Volumn 234, Issue 2, 2017, Pages 199-209

  Durgam, Suresh ^a   Greenberg, William M ^a   Li, Dayong ^a   Lu, Kaifeng ^a   Laszlovszky, Istvan ^b   Nemeth, Gyorgy ^b   Migliore, Raffaele ^a   Volk, Stephen ^c  

^a Allergan plc   (United States)

^b GEDEON RICHTER LTD   (Hungary)

^c Apostle Clinical Trials   (United States)

Author keywords

Atypical antipsychotic; Cariprazine; Dopamine antagonist; Open label; Safety; Schizophrenia

Indexed keywords

BENZATROPINE; CARIPRAZINE; CHLORAL HYDRATE; CITALOPRAM; DIPHENHYDRAMINE; ESCITALOPRAM; ESZOPICLONE; FLUOXETINE; FLUVOXAMINE; LORAZEPAM; PLACEBO; PROLACTIN; PROPRANOLOL; RISPERIDONE; SERTRALINE; VALPROATE SEMISODIUM; ZALEPLON; ZOLPIDEM; NEUROLEPTIC AGENT; PIPERAZINE DERIVATIVE;

ADULT; AKATHISIA; ANXIETY DISORDER; ARTICLE; BLEPHARITIS; BLURRED VISION; CARDIOVASCULAR PARAMETERS; CATARACT; CLINICAL GLOBAL IMPRESSION SCALE; CONSTIPATION; CONTROLLED STUDY; CORNEA OPACITY; DIARRHEA; DISEASE ASSOCIATION; DISEASE SEVERITY; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; ECG ABNORMALITY; EXTRAPYRAMIDAL SYMPTOM; FEMALE; HEADACHE; HOSTILITY; HUMAN; INSOMNIA; IRRITABILITY; LONG TERM CARE; MAJOR CLINICAL STUDY; MALE; METABOLIC PARAMETERS; MULTICENTER STUDY; OPEN STUDY; ORTHOSTATIC HYPOTENSION; OUTPATIENT CARE; PHASE 2 CLINICAL TRIAL (TOPIC); POSITIVE AND NEGATIVE SYNDROME SCALE; PRIORITY JOURNAL; PROLACTIN BLOOD LEVEL; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESTLESSNESS; RHINOPHARYNGITIS; SCHIZOPHRENIA; SEDATION; SIDE EFFECT; SOMNOLENCE; SUICIDAL BEHAVIOR; TREMOR; WEIGHT GAIN; CHEMICALLY INDUCED; CLINICAL TRIAL; DRUG EFFECTS; FOLLOW UP; MIDDLE AGED; RANDOMIZED CONTROLLED TRIAL; TIME FACTOR; TREATMENT OUTCOME; YOUNG ADULT;

ADULT; AKATHISIA, DRUG-INDUCED; ANTIPSYCHOTIC AGENTS; DOUBLE-BLIND METHOD; FEMALE; FOLLOW-UP STUDIES; HUMANS; MALE; MIDDLE AGED; PIPERAZINES; SCHIZOPHRENIA; TIME FACTORS; TREATMENT OUTCOME; TREMOR; WEIGHT GAIN; YOUNG ADULT;

EID: 84994252975     PISSN: 00333158     EISSN: 14322072     Source Type: Journal    
DOI: 10.1007/s00213-016-4450-3     Document Type: Article

References (40)

1. Ascher-Svanum H, Nyhuis AW, Stauffer V, Kinon BJ, Faries DE, Phillips GA, Schuh K, Awad AG, Keefe R, Naber D (2010) Reasons for discontinuation and continuation of antipsychotics in the treatment of schizophrenia from patient and clinician perspectives. Curr Med Res Opin 26:2403–2410
2. Barnes TR (1989) A rating scale for drug-induced akathisia. Br J Psychiatry 154:672–676
3. Caravaggio F, Blumberger D, Nakajima S, Mulsant B, Graff-Guerrerero A (2014) Occupancy of dopamine D3 receptors by aripiprazole in treatment resistant late-life depressed patients depends on length of treatment as evidenced by in vivo imaging with [11C]-(+)-PHNO. Am J Geriatr Psychitary 22:S83–S84
4. Coric V, Stock EG, Pultz J, Marcus R, Sheehan DV (2009) Sheehan Suicidality Tracking Scale (Sheehan-STS): preliminary results from a multicenter clinical trial in generalized anxiety disorder. Psychiatry (Edgmont) 6:26–31
5. Debelle M, Németh G, Szalai E, Szatmári B, Harsányi J, Barabássy A, Laszlovszky I (2015) Cariprazine as monotherapy for the treatment of schizophrenia patients with predominant negative symptoms: a double-blind, active controlled trial. Eur Neuropsychopharamcol 25:S510
6. Durgam S, Starace A, Li D, Migliore R, Ruth A, Nemeth G, Laszlovszky I (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, Nemeth G, Meltzer HY (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, Earley W, Guo H, Li D, Nemeth G, Laszlovszky I, Fava M, Montgomery SA (2016a) Efficacy and safety of adjunctive cariprazine in inadequate responders to antidepressants: a randomized, double-blind, placebo-controlled study in adult patients with major depressive disorder. J Clin Psychiatry 77:371–378
9. Durgam S, Earley W, Li R, Li D, Lu K, Laszlovszky I, Fleischhacker WW, Nasrallah HA (2016b) Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. Schizophr Res 176:264–271
10. Durgam S, Earley W, Lipschitz A, Guo H, Laszlovszky I, Nemeth G, Vieta E, Calabrese JR, Yatham LN (2016c) An 8-week randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of cariprazine in patients with bipolar I depression. Am J Psychiatry 173:271–281
11. Girgis RR, Slifstein M, D'Souza D, Lee Y, Periclou A, Ghahramani P, Laszlovszky I, Durgam S, Adham N, Nabulsi N, Huang Y, Carson RE, Kiss B, Kapás M, Abi-Dargham A, Rakhit A (2016) Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [(11)C]-(+)-PHNO. Psychopharmacology 233:3503–3512
12. Goff DC, Sullivan LM, McEvoy JP, Meyer JM, Nasrallah HA, Daumit GL, Lamberti S, D’Agostino RB, Stroup TS, Davis S (2005) A comparison of ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls. Schizophr Res 80:45–53
13. Graff-Guerrero A, Mamo D, Shammi CM, Mizrahi R, Marcon H, Barsoum P, Rusjan P, Houle S, Wilson AA, Kapur S (2009) The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study with [11C]-(+)-PHNO. Arch Gen Psychiatry 66:606–615
14. Gross G, Drescher K (2012) The role D (3) receptors in antipsychotic activity and cognitive functions. Handb Exp Pharmacol:167–210
15. Guy W (1976a) Abnormal involuntary movement scale (AIMS). ECDEU assessment manual for psychopharmacology 338:534–537
16. Guy W (1976b) The clinician global severity and impression scales. ECDEU assessment manual for psychopharmacology. Rockville, MD: National Institute of. Mental Health:218–222 DHEW Publication No. 76-338
17. Gyertyán I, Saghy K, Laszy J, Elekes O, Kedves R, Gemesi LI, Pasztor G, Zajer-Balazs M, Kapas M, Agai Csongor E, Domany G, Kiss B, Szombathelyi Z (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 Schmiedeberg’s Arch Pharmacol 378:529–539
18. Gyertyán I, Kiss B, Sághy K, Laszy J, Szabó G, Szabados T, Gémesi LI, Pásztor G, Zájer-Balázs M, Kapás M, Csongor EA, Domány G, Tihanyi K, Szombathelyi Z (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
19. Higashi K, Medic G, Littlewood KJ, Diez T, Granstrom O, De Hert M (2013) Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review. Ther Adv Psychopharmacol 3:200–218
20. Joyce JN, Millan MJ (2005) Dopamine D3 receptor antagonists as therapeutic agents. Drug Discov Today 10:917–925
21. Kane JM, Fleischhacker WW, Hansen L, Perlis R, Pikalov A 3rd, Assuncao-Talbott S (2009) Akathisia: an updated review focusing on second-generation antipsychotics. J Clin Psychiatry 70:627–643
22. Kane JM, Zukin S, Wang Y, Lu K, Ruth A, Nagy K, Laszlovszky I, Durgam S (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
23. Kapur S, Seeman P (2001) Does fast dissociation from the dopamine d (2) receptor explain the action of atypical antipsychotics?: a new hypothesis. Am J Psychiatry 158:360–369
24. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276
25. Kiss B, Laszlovszky I, Horvath A, Nemethy Z, Schmidt E, Bugovics G, Fazekas K, Gyertyan I, Agai-Csongor E, Domany G, Szombathelyi Z (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 Schmiedeberg’s Arch Pharmacol 378:515–528
26. Kiss B, Horváth A, Némethy Z, Schmidt É, Laszlovszky I, Bugovics G, Fazekas K, Hornok K, Orosz S, Gyertyán I (2010) Cariprazine (RGH-188), a dopamine D3 receptor-preferring, D3/D2 dopamine receptor antagonist–partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther 333:328–340
27. Leriche L, Diaz J, Sokoloff P (2004) Dopamine and glutamate dysfunctions in schizophrenia: role of the dopamine D3 receptor. Neurotox Res 6:63–71
28. Leucht S, Pitschel-Walz G, Abraham D, Kissling W (1999) Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 35:51–68
29. Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382:951–962
30. Leung JY, Barr AM, Procyshyn RM, Honer WG, Pang CC (2012) Cardiovascular side-effects of antipsychotic drugs: the role of the autonomic nervous system. Pharmacol Ther 135:113–122
31. Miller DD (2004) Atypical antipsychotics: sleep, sedation, and efficacy. Prim Care Companion J Clin Psychiatry 6:3–7
32. Mizrahi R, Agid O, Borlido C, Suridjan I, Rusjan P, Houle S, Remington G, Wilson AA, Kapur S (2011) Effects of antipsychotics on D3 receptors: a clinical PET study in first episode antipsychotic naive patients with schizophrenia using [11C]-(+)-PHNO. Schizophr Res 131:63–68
33. Nasrallah HA (2008) Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 13:27–35
34. Nord M, Farde L (2011) Antipsychotic occupancy of dopamine receptors in schizophrenia. CNS Neurosci Ther 17:97–103
35. Perkins DO (2002) Predictors of noncompliance in patients with schizophrenia. J Clin Psychiatry 63:1121–1128
36. Robinson D, Woerner MG, Alvir JMJ, Bilder R, Goldman R, Geisler S, Koreen A, Sheitman B, Chakos M, Mayerhoff D (1999) Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 56:241–247
37. Simpson GM, Angus JW (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 212:11–19
38. Weiden PJ (2007) EPS profiles: the atypical antipsychotics are not all the same. J Psychiatr Pract 13:13–24
39. Yamada K, Watanabe K, Nemoto N, Fujita H, Chikaraishi C, Yamauchi K, Yagi G, Asai M, Kanba S (2006) Prediction of medication noncompliance in outpatients with schizophrenia: 2-year follow-up study. Psych Res 141:61–69
40. Zimnisky R, Chang G, Gyertyán I, Kiss B, Adham N, Schmauss C (2013) Cariprazine, a dopamine D (3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse. Psychopharmacology 226:91–100