PMID- 33854317
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240407
IS  - 1176-6328 (Print)
IS  - 1178-2021 (Electronic)
IS  - 1176-6328 (Linking)
VI  - 17
DP  - 2021
TI  - Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled 
      Analysis of Eight Phase II/III Studies.
PG  - 957-970
LID - 10.2147/NDT.S301225 [doi]
AB  - BACKGROUND: Long-term treatment with antipsychotic agents is indicated for 
      patients with schizophrenia, but treatment is associated with adverse events 
      (AEs) that contribute to medication discontinuation and nonadherence. 
      Understanding drug safety profiles is critical to avoid unwanted side effects. 
      Cariprazine is a potent dopamine D(3)/D(2) receptor partial agonist that is 
      approved for the treatment of adults with schizophrenia (EU, US) and acute 
      manic/mixed and depressive episodes associated with bipolar I disorder (US). 
      METHODS: Post hoc analyses were conducted to characterize the safety profile of 
      cariprazine within the recommended 1.5-6 mg/d dose range for schizophrenia; data 
      from 8 short- or long-term clinical trials were analyzed. RESULTS: In the pooled 
      cariprazine-treated safety population (n=2048), the rate of study completion was 
      52.8%, with withdrawal of consent, insufficient response, and AEs the most common 
      reasons for premature discontinuation. The most commonly reported AEs (>10%) in 
      the overall cariprazine-treatment group were akathisia (14.6%), insomnia (14.0%), 
      and headache (12.1%); most AEs were considered mild (71.0%) or moderate (26.5%). 
      Most akathisia was mild/moderate (97.5%) and >93% of patients remained on 
      treatment; akathisia events were managed by rescue medications (56.3%) or dose 
      reduction (18.3%). The metabolic profile of cariprazine was neutral in patients 
      with short- and long-term exposure; mean weight gain was 1 kg for overall 
      cariprazine, with an AE of weight increased reported for 5.1%. Other AEs of 
      special interest that occurred at >3% for overall cariprazine were extrapyramidal 
      disorder (7.0%), sedation (3.7%), and somnolence (3.1%); prolactin elevation, 
      cognition impairment, sexual dysfunction, suicidality, and QT prolongation 
      occurred at </=1%. CONCLUSION: Akathisia, the most common cariprazine-related AE, 
      was mild/moderate and resulted in few study discontinuations; symptoms were well 
      managed and most patients remained on treatment. Results of this analysis 
      indicated that cariprazine in the recommended dose range was safe and generally 
      well tolerated in patients with schizophrenia. TRIAL REGISTRATION: Studies 
      registered with ClinicalTrials.gov (NCT00404573, NCT01104779, NCT00694707, 
      NCT01104766, NCT01104792, NCT00839852, and NCT01412060) and EudraCT 
      (2012-005485-36).
CI  - (c) 2021 Barabassy et al.
FAU - Barabassy, Agota
AU  - Barabassy A
AD  - Medical Division, Gedeon Richter Plc, Budapest, Hungary.
FAU - Sebe, Barbara
AU  - Sebe B
AD  - Medical Division, Gedeon Richter Plc, Budapest, Hungary.
FAU - Acsai, Karoly
AU  - Acsai K
AD  - Medical Division, Gedeon Richter Plc, Budapest, Hungary.
FAU - Laszlovszky, Istvan
AU  - Laszlovszky I
AD  - Medical Division, Gedeon Richter Plc, Budapest, Hungary.
FAU - Szatmari, Balazs
AU  - Szatmari B
AD  - Medical Division, Gedeon Richter Plc, Budapest, Hungary.
FAU - Earley, Willie R
AU  - Earley WR
AD  - Clinical Development, AbbVie, Madison, NJ, USA.
FAU - Nemeth, Gyorgy
AU  - Nemeth G
AD  - Medical Division, Gedeon Richter Plc, Budapest, Hungary.
LA  - eng
SI  - ClinicalTrials.gov/NCT00839852
SI  - ClinicalTrials.gov/NCT01412060
SI  - ClinicalTrials.gov/NCT01104779
SI  - ClinicalTrials.gov/NCT00694707
SI  - ClinicalTrials.gov/NCT00404573
SI  - ClinicalTrials.gov/NCT01104766
SI  - ClinicalTrials.gov/NCT01104792
PT  - Journal Article
DEP - 20210407
PL  - New Zealand
TA  - Neuropsychiatr Dis Treat
JT  - Neuropsychiatric disease and treatment
JID - 101240304
EIN - Neuropsychiatr Dis Treat. 2021 May 17;17:1481. PMID: 34040374
PMC - PMC8040316
OTO - NOTNLM
OT  - atypical antipsychotic
OT  - cariprazine
OT  - post hoc analysis
OT  - safety and tolerability
OT  - schizophrenia
COIS- Agota Barabassy, Barbara Sebe, Karoly Acsai, Istvan Laszlovszky, Balazs Szatmari 
      and Gyorgy Nemeth are employees of Gedeon Richter Plc. Barbara Sebe and Karoly 
      Acsai report personal fees from Gedeon Richter Plc., outside the submitted work. 
      Istvan Laszlovszky reports personal fees from Gedeon Richter Plc., during the 
      conduct of the study; in addition, Istvan Laszlovszky has a patent cariprazine 
      issued. Balazs Szatmari reports personal fees from Gedeon Richter Plc., outside 
      the submitted work; in addition, Balazs Szatmari has a patent cariprazine issued. 
      Willie R. Earley reports being an employee of AbbVie, and share- or stock-holder 
      of AbbVie, AstraZeneca and Eli Lilly; being a former employee of Allergan and 
      Forest LP during the conduct of the study and outside the submitted work; and 
      being previously employed with Forest LP, AstraZeneca, and Eli Lilly outside the 
      submitted work. Gyorgy Nemeth reports personal fees from Gedeon Richter Plc., 
      outside the submitted work; in addition, Dr Gyorgy Nemeth has a patent 
      cariprazine issued. The authors report no other potential conflicts of interest 
      for this work.
EDAT- 2021/04/16 06:00
MHDA- 2021/04/16 06:01
PMCR- 2021/04/07
CRDT- 2021/04/15 07:15
PHST- 2021/01/09 00:00 [received]
PHST- 2021/03/12 00:00 [accepted]
PHST- 2021/04/15 07:15 [entrez]
PHST- 2021/04/16 06:00 [pubmed]
PHST- 2021/04/16 06:01 [medline]
PHST- 2021/04/07 00:00 [pmc-release]
AID - 301225 [pii]
AID - 10.2147/NDT.S301225 [doi]
PST - epublish
SO  - Neuropsychiatr Dis Treat. 2021 Apr 7;17:957-970. doi: 10.2147/NDT.S301225. 
      eCollection 2021.