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Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia

Results From an International, Phase III Clinical Trial

Kane, John M. MD*; Zukin, Stephen MD; Wang, Yao MD; Lu, Kaifeng PhD; Ruth, Adam PhD§; Nagy, Krisztián MD; Laszlovszky, István PharmD, PhD; Durgam, Suresh MD

Author Information
Journal of Clinical Psychopharmacology: August 2015 - Volume 35 - Issue 4 - p 367-373
doi: 10.1097/JCP.0000000000000346


Schizophrenia is a severe and chronic disorder characterized by the breakdown of thought processes and deficits in emotional response. Symptoms of schizophrenia are divided into 3 broad domains consisting of positive (eg, delusions, hallucinations, disorganized speech), negative (eg, lack of emotion, anhedonia, social withdrawal), and cognitive (eg, attention and memory deficits) symptoms. Antipsychotics, the cornerstone of schizophrenia treatment, are generally effective on positive symptoms but have shown limited efficacy on negative symptoms and cognitive dysfunction,1 which are the disorder characteristics most strongly associated with decreased quality of life.2–7 In addition, response and tolerability to specific antipsychotics may differ in individual patients, potentially due to pharmacological differences between agents in this class. This variability underscores the importance of identifying new compounds with different mechanisms of action to improve treatment outcomes for all patients.

Blockade of dopamine D2 receptors is thought to be necessary for antipsychotic action,1 but targeting other receptors may provide additional benefits in schizophrenia. Converging lines of evidence suggest that the D3 receptor may play a role in modulating mood and cognition8–12 and it has emerged as a potential target for the treatment of schizophrenia and bipolar disorder.13,14 As such, it was hypothesized that a compound with high affinity for both D3 and D2 receptors may provide strong antipsychotic efficacy for positive symptoms with a potential benefit in negative symptoms and cognitive impairment.14

Cariprazine, an orally active and potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, was identified as an atypical antipsychotic candidate that had a distinct pharmacological profile. It is currently in clinical development for the treatment of schizophrenia, bipolar mania, bipolar depression, and the adjunctive treatment of major depressive disorder (MDD). Cariprazine, like aripiprazole, is an atypical antipsychotic that acts as a partial agonist at D2 receptors, a feature that may contribute to a more favorable safety profile compared with D2 receptor antagonists. Cariprazine, unlike other antipsychotics, has a nearly 10-fold greater in vitro affinity for D3 versus D2 receptors15 and displays high in vivo occupancy of both D2 and D3 receptors in rats16 and humans.17 In preclinical rodent models, cariprazine displayed potent antipsychotic-like efficacy18 and demonstrated D3 receptor–dependent anti–anhedonic-like19 and procognitive20 effects. These findings suggest that cariprazine may have potential for clinical efficacy across a broad range of symptoms associated with schizophrenia including negative symptoms and cognitive deficits.

In phase II (cariprazine 1.5, 3.0, or 4.5 mg/d)21 and phase III (3 or 6 mg/d)22 randomized, placebo-controlled clinical studies in patients with acute exacerbation of schizophrenia, cariprazine was effective and generally well tolerated at all doses tested (1.5–6 mg/d). The phase III study reported here was designed to evaluate cariprazine 3 to 6 and 6 to 9 mg/d in patients with schizophrenia.


Study Design

This double-blind, placebo-controlled, parallel-group study (NCT01104779) was conducted to evaluate the efficacy, safety, and tolerability of fixed/flexible doses of cariprazine 3 to 6 or 6 to 9 mg/d in patients with acute exacerbation of schizophrenia. The study was conducted between April 2010 and December 2011 at 41 centers in the United States, India, Colombia, and South Africa (Supplementary Table A, Supplemental Digital Content 1,; the protocol was approved by an institutional review board (United States) or ethics committee (non–US sites). ICH-E6 Good Clinical Practice guidelines were followed and all participants provided written informed consent.

This 9-week study consisted of a washout period (up to 7 days), 6 weeks of double-blind treatment, and 2 weeks of safety follow-up. Patients were randomized (1:1:1) to placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Patients randomized to cariprazine received 1.5 mg on day 1 and 3.0 mg on days 2 and 3. The 3 to 6 mg/d group remained at 3.0 mg until the end of week 2 of double-blind treatment; starting on day 4, the 6 to 9 mg/d group received 6.0 mg until the end of week 2 of double-blind treatment. In cases of inadequate response (<20% improvement from baseline on Positive and Negative Syndrome Scale [PANSS]23,24 total score and a Clinical Global Impressions-Severity [CGI-S]25 score ≥ 4), cariprazine dose was increased at the end of week 2. In the 3 to 6 mg/d group, patients received 4.5 mg/d for days 14 to 15 and 6.0 mg/d thereafter; in the 6 to 9 mg/d group, patients received 7.5 mg/d for days 14 to 15 and to 9.0 mg/d thereafter. Patients who did not qualify as inadequate responders or had significant tolerability issues did not receive a dose increase. Dosage was fixed from the end of week 3 to week 6.

Patients were hospitalized for washout/screening and at least 4 weeks of double-blind treatment. Between days 28 and 42, patients with CGI-S score of 3 or less (mildly ill or better), no significant risk of suicide or violent behavior, and ready for discharge in the opinion of the investigator were eligible for discharge.

Inclusion Criteria

Men and women aged 18 to 60 years with a current diagnosis of schizophrenia (paranoid, disorganized, catatonic, or undifferentiated type) defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision were included. Participants had been diagnosed for 1 year or more and had a current psychotic episode of less than 2 weeks' duration with at least 1 psychotic episode that required hospitalization or change in antipsychotic therapy during the previous year. A CGI-S score of 4 or higher, PANSS total score of 80 or more and 120 or less, and a score of 4 or higher on at least 2 of the following 4 PANSS items: delusions, hallucinatory behavior, conceptual disorganization, or suspiciousness/persecution were required.

Exclusion Criteria

Patients were excluded for diagnoses of schizoaffective, schizophreniform, bipolar I or II disorders, or other Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision Axis II disorders of sufficient severity to interfere with participation; first psychotic episode; substance abuse/dependence (past 3 months); suicide attempt (past 2 years); suicide risk (psychiatric interview or Columbia-Suicide Severity Rating scale [C-SSRS])26; treatment-resistant schizophrenia (ie, poor response to ≥2 antipsychotics during the past 2 years); or any significant/unstable medical condition that might interfere with study participation. Other reasons for exclusion included body mass index of less than 18 or greater than 40 kg/m2; pregnancy or breastfeeding; electroconvulsive therapy in the past 3 months; prior depot neuroleptic treatment; or clozapine in the past 10 years (except low-dose, episodic use for insomnia). Medications with psychotropic activity were not allowed except for lorazepam (for agitation, irritability, hostility, restlessness); zolpidem, zaleplon, chloral hydrate, or eszopiclone (for insomnia); and diphenhydramine, benztropine, or propranolol (for extrapyramidal symptoms [EPS]).

Outcome Assessments

The PANSS and CGI-S were administered at screening (week −1), baseline (week 0), and all double-blind study visits (weeks 1–6). Additional assessments included the CGI-Improvement (CGI-I)25 (weeks 1-6), 16-item Negative Symptom Assessment (NSA-16)27 (weeks 0, 2, 4, and 6), Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4)28 (weeks 0 and 6), Cognitive Drug Research System (CDR) Attention Battery Tests29 (weeks 0, 3, and 6), and Color Trails Test (CTT)30 (weeks 0, 3, and 6).

Safety assessments included treatment-emergent adverse events (TEAEs), physical examination, clinical laboratory tests, vital signs, ophthalmologic examination (including visual acuity, intraocular pressure, color discrimination, and slit-lamp examination; Lens Opacities Classification System III scores were used for grading lens opacity), C-SSRS, and EPS scales (Abnormal Involuntary Movement Scale [AIMS],31 Barnes Akathisia Rating Scale [BARS] items 1 to 3,32 Simpson-Angus Scale [SAS]33).

Statistical Analyses

Safety analyses were based on the Safety Population (all randomized patients who took ≥1 dose of double-blind study drug); efficacy analyses were based on the Intent-to-Treat Population (all patients in the Safety Population who had ≥1 postbaseline PANSS total score assessment). The primary and secondary efficacy parameters were change from baseline to week 6 in PANSS total score and CGI-S score, respectively, analyzed using a mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects and baseline value and baseline value-by-visit interaction as covariates; an unstructured covariance matrix was used to model the covariance of within-patient scores. A matched parallel gatekeeping procedure34 was used to control for multiple comparisons across the primary and secondary hypotheses; significance on the secondary endpoint for a dose level would not be claimed unless its corresponding primary hypothesis was found significant.

Sensitivity analyses for the primary efficacy parameter included a pattern-mixture model based on non–future-dependent missing value restrictions35 and analysis of covariance (ANCOVA) using last observation carried forward (LOCF), with treatment group and study center as factors and baseline score as a covariate.

Additional efficacy parameters (and analytical method) included change from baseline to week 6 in PANSS Positive and Negative subscale scores, and NSA-16 (MMRM); SQLS-R4 (ANCOVA, LOCF values); and CTT and CDR Attention Battery scores (Wilcoxon rank sum test, LOCF). Week 6 CGI-I score (MMRM using CGI-S baseline score) and PANSS responders (≥30% improvement from baseline) (logistic regression model, LOCF) were also evaluated.

For all efficacy parameters, all statistical tests were 2-sided hypothesis tests performed at the 5% level of significance for main effects; additional and by-visit efficacy analyses were not controlled for multiple comparisons. For all efficacy measures, statistical significance was defined as P < 0.05.

Treatment groups were compared for percentage of premature discontinuation using the Fisher exact test36 and for differences in demographic and baseline characteristics using an analysis of variance for continuous variables and Cochran–Mantel–Haenszel tests37 for categorical variables. Treatment-emergent parkinsonism (SAS score: baseline ≤3 and any postbaseline >3) and akathisia (BARS score: baseline ≤2 and any postbaseline >2) were evaluated. All safety measures were analyzed using descriptive statistics.


Baseline demographics and disease characteristics were similar among groups; patients had moderate to severe schizophrenia, as indicated by PANSS38 and CGI-S scores. Patient populations and the most common reasons for premature discontinuation are presented in Table 1.

Patient Disposition and Baseline Characteristics


The least squares mean difference (LSMD) and 95% confidence interval (CI) versus placebo for PANSS total score change at week 6 (primary efficacy parameter) was −6.8 (−11.3, −2.4) for cariprazine 3 to 6 mg/d (P = 0.003) and −9.9 (−14.5, −5.3) for cariprazine 6 to 9 mg/d (P < 0.001); statistical significance versus placebo was detected beginning at week 1 for cariprazine for 6 to 9 mg/d and at week 2 for 3 to 6 mg/d (Fig. 1); significant differences persisted until the end of study in both cariprazine-dose groups. The robustness of the primary analyses was supported by pattern-mixture model (data not shown) and LOCF sensitivity analyses (LSMD [95% CI] versus placebo: −6.3 [−10.2, −2.4] for cariprazine 3 to 6 mg/d [P < 0.01] and −8.0 [−11.9, −4.0] for 6 to 9 mg/d [P < 0.001]). The between-group difference for mean change in CGI-S scores at week 6 (secondary efficacy parameter) was statistically significant in both cariprazine groups versus placebo (LSMD [95% CI]: 3–6 mg/d = −0.3 [−0.6, −0.1], P = 0.012; 6–9 mg/d = −0.5 [−0.8, −0.3], P < 0.001); statistically significant advantage was observed beginning at week 1 and week 3 for the 6 to 9 and 3 to 6 mg/d groups, respectively (Fig. 2). Mean changes from baseline for primary, secondary, and additional efficacy outcomes are presented in Table 2.

Change from baseline in PANSS total score (MMRM, ITT Population). ITT, intent-to-treat; MMRM, mixed-effects model with repeated measures; PANSS, Positive and Negative Syndrome Scale; *P < 0.05; **P < 0.01; ***P < 0.001; vs placebo.
Change from baseline in CGI-S score (MMRM, ITT Population). ITT, intent-to-treat; MMRM, mixed-effects model with repeated measures; CGI-S, Clinical Global Impressions-Severity; *P < 0.05; **P < 0.01; ***P < 0.001; vs placebo.
Efficacy Outcomes: Mean Change From Baseline to Week 6 (ITT Population, MMRM)

Statistically significantly greater improvements versus placebo were observed for cariprazine 3 to 6 and 6 to 9 mg/d on the PANSS Positive subscale and CGI-I; cariprazine 6 to 9 mg/d also showed statistically significantly improvement versus placebo on negative symptoms (PANSS Negative subscale and NSA-16 total scores). Larger and statistically significant reductions in score change from baseline to week 6 were observed for cariprazine 3 to 6 mg/d versus placebo in SQLS-R4 total score (P = 0.0435) and vitality score (P = 0.0040); numerical improvements on SQLS-R4 outcomes were observed for cariprazine 6 to 9 mg/d versus placebo, but the differences were not statistically significant. No significant differences for either cariprazine group versus placebo were observed on the CDR Attention Battery or CTT tests (data not shown). PANSS response rate was numerically higher, but not statistically different, for cariprazine 3 to 6 mg/d (28.6%) and 6 to 9 mg/d (34.7%) versus placebo (24.8%).


Extent of Exposure

The mean treatment duration was 32.1 days for placebo and cariprazine 6 to 9 mg/d, and 33.2 days for cariprazine 3 to 6 mg/d; mean final daily doses were 5.2 and 7.7 mg/d for the cariprazine 3 to 6 and 6 to 9 mg/d groups, respectively.

Adverse Events

A summary of double-blind adverse events (AEs) is presented in Table 3. Most TEAEs were of mild/moderate intensity for placebo (95%) and cariprazine 3 to 6 mg/d (97%) and 6 to 9 mg/d (98%) groups. Most serious AEs (SAEs) involved worsening of schizophrenia. Eight SAEs in 7 patients (1 placebo [exacerbation of schizophrenia], 3 cariprazine 3–6 mg/d (hyponatremia, psychotic relapse, psychotic exacerbation [1 each; all discontinued]); 3 cariprazine 6–9 mg/d (hepatitis, worsening of psychosis [1 each], irregular pulse and increased blood pressure [1 patient; all discontinued]) were considered related to study drug. Lorazepam use to control agitation was similar between placebo (80%) and cariprazine groups (both groups, 82%).

Adverse Events During Double-Blind Treatment Period (Safety Population)

Laboratory Parameters, Vital Signs, ECG, and Ophthalmologic Parameters

Mean changes in vital signs were generally small in all treatment groups (Supplementary Table B, Supplemental Digital Content 2, There were no potentially clinically significant (PCS) changes in vital signs in the cariprazine treatment groups with the exception of 1 (0.7%) cariprazine 3 to 6 mg/d patient with decreased systolic blood pressure (≥90 mm Hg and a decrease ≥20 mm Hg); 2 placebo patients (1.4%) had PCS decreases in systolic blood pressure. Incidences of orthostatic hypotension (reduction of ≥20 or ≥10 mm Hg in systolic or diastolic blood pressure, respectively, during change from supine to standing position) were similar for placebo and cariprazine 6 to 9 mg/d groups (13%), with a lower incidence in cariprazine 3 to 6 mg/d group (7%). Orthostatic hypotension was reported as a TEAE in 4 placebo patients; it was not reported in any cariprazine-treated patients.

Mean changes in metabolic parameters were also generally small and similar between groups. Incidence of metabolic TEAEs was similar between groups; only hypertriglyceridemia (2 placebos, 1 cariprazine 6–9 mg/d) and increased blood cholesterol (1 placebo, 1 cariprazine 6–9 mg/d) were reported in more than 1 patient. Only 5 patients (2 placebo, 1 cariprazine 3–6 mg/d, and 2 cariprazine 6–9 mg/d) shifted from non–PCS levels at baseline to PCS levels during treatment for cholesterol, triglyceride, or glucose parameters and were associated with metabolic AEs. Mean changes in body weight and waist circumference were small and similar between groups. Increases from baseline of 7% or more body weight were more common with cariprazine 3 to 6 mg/d (8%) and 6 to 9 mg/d (11%) than placebo (4%).

Slightly greater mean increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for cariprazine was noted, primarily due to high values in 3 patients. PCS changes in ALT and AST (≥3 times upper limit of normal [ULN]) were infrequent, with similar incidence in the cariprazine and placebo groups (ALT: 1% in all treatment groups; AST: placebo, 0%; 3–6 mg/d, 0%; 6–9 mg/d, 1%); no patient met Hy's law criteria (ALT or AST ≥3 times ULN concurrent with total bilirubin ≥2 times ULN and alkaline phosphatase <2 times ULN).39 Prolactin levels decreased in all 3 treatment groups. There were no QTcB or QTcF interval increases greater than 500 milliseconds observed in this study. Mean changes in ophthalmologic parameters were small and similar between groups. The most common eye disorder–related TEAE was blurred vision, which occurred in 0% of patients in the placebo group, 1% of patients in the cariprazine 3 to 6 mg/d group, and 3% of patients in the cariprazine 6 to 9 mg/d group. No incidence of cataracts was reported in the study.

Extrapyramidal Symptoms

All cariprazine-related incidences of akathisia, the most common EPS-related TEAE (Table 3), were mild or moderate in intensity; no cariprazine 3–6 mg/d patients and 1 cariprazine 6–9 mg/d patient discontinued prematurely due to akathisia. There were no other discontinuations due to EPS-related AEs in any cariprazine treatment group. Between-group mean changes on EPS scales were generally similar; SAS total score was slightly higher for cariprazine 6 to 9 mg/d versus placebo (Supplementary Table B, Supplemental Digital Content 2, More cariprazine 3 to 6 mg/d (9%) and 6 to 9 mg/d (17.0%) patients than placebo (5%) patients had treatment-emergent Parkinsonism (SAS score ≤3 at baseline and >3 postbaseline); more cariprazine 3 to 6 mg/d (22%) and 6 to 9 mg/d (13%) than placebo (6%) had treatment-emergent akathisia (BARS score ≤2 at baseline and >2 postbaseline). The use of anti-Parkinson medications was higher with cariprazine 3 to 6 mg/d (16%) and 6 to 9 mg/d (24%) than placebo (3%); use of propranolol for akathisia was also higher with cariprazine 3 to 6 mg/d (12%) and 6 to 12 mg/d (12%) than placebo (4%).


Results from this study in patients with acute exacerbation of schizophrenia demonstrated significantly greater improvement for cariprazine 3 to 6 or 6 to 9 mg/d versus placebo on the primary (PANSS total score) and secondary (CGI-S) efficacy parameters. Significant treatment differences in PANSS total score were observed as early as week 1 for the cariprazine 6 to 9 mg/d group and week 2 for the cariprazine 3 to 6 mg/d group. These results were consistent with other positive phase II and III studies supporting the efficacy of cariprazine 1.5, 3.0, 4.5, and 6.0 mg/d in patients with schizophrenia.21,22

Efficacy on the positive symptoms of schizophrenia is a hallmark of atypical antipsychotic treatments. Negative symptoms are associated with poor functional outcomes and persistent impairment and these symptoms have been only modestly responsive to currently available treatments.40 Identification of effective compounds for treating negative symptoms remains an unmet need in the treatment of schizophrenia. Behavioral experiments in rodent models revealed anti–anhedonic-like effects with cariprazine,19,41 that were found to be mediated by the D3 receptor,19 suggesting potential utility for treating negative symptoms and depressed mood associated with schizophrenia. It is still unknown whether the D3 receptor activity of cariprazine directly translates into clinical benefits on the symptom domains related to mood and/or negative symptoms, although positive results from recent phase II clinical studies of cariprazine for bipolar I depression42 and as an adjunctive treatment for MDD43 have provided some support for this hypothesis. Few antipsychotic compounds have demonstrated efficacy in bipolar depression and MDD, suggesting that the distinct D3 receptor activity of cariprazine may contribute to its efficacy in these disorders.

In this study, statistically significant or numerically better results for cariprazine versus placebo on the PANSS Negative subscale and the NSA-16 in the current study further support the efficacy potential on negative symptoms. These results are consistent with a previous cariprazine study in patients with schizophrenia that demonstrated significant differences versus placebo on negative symptom measures at doses as low as 1.5 mg/d.21 However, as the study population was comprised primarily of patients with moderate or severe positive symptoms (psychosis), it is possible that the improvements in negative symptoms are secondary to the large improvements in positive symptoms. Future studies in patients with predominantly negative symptoms are planned to more fully elucidate the effect of cariprazine and its distinct pharmacological profile on this symptom cluster.

Evidence suggests that even after significant improvements in psychotic symptoms, patients with schizophrenia continue to experience poor quality of life due to residual negative symptoms, depression/anxiety, or cognitive impairment.2–7,44–48 Of note here, statistically significant or numerical reductions for both doses of cariprazine relative to placebo on the SQLS-R4 suggest cariprazine may also be associated with improvements in domains related to quality of life. Further analyses are needed to better characterize the effects of cariprazine on health-related quality of life.

Cariprazine was generally well tolerated in this study. Most TEAEs were considered mild or moderate in severity; discontinuation rates due to AEs were similar between the cariprazine and placebo groups. Similar to some drugs in this class, EPS-related TEAEs were more common with cariprazine than with placebo. Akathisia was the most common TEAE, which was reported in 16% and 17% of patients in the cariprazine 3 to 6 and 6 to 9 mg/d groups, respectively, compared with 3% of placebo patients. All incidences of akathisia in the cariprazine groups were considered mild or moderate in severity and were generally controlled with propranolol. Only 1 patient in either cariprazine group discontinued prematurely due to akathisia (6–9 mg/d); there were no discontinuations due to other EPS-related TEAEs in either cariprazine treatment groups. Mean changes in EPS scales were similar between the cariprazine groups and placebo, with the exception of slightly higher increases on the SAS in the cariprazine 6 to 9 mg/d group.

More than 50% of patients with schizophrenia have comorbid psychiatric or medical conditions associated with worse prognosis and elevated mortality compared with the general population.49 Some second-generation antipsychotics induce substantial weight gain and metabolic AEs, increasing the risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease in an already vulnerable patient population.50 Consistent with previous cariprazine studies in schizophrenia21 and bipolar I disorder,51 changes in metabolic parameters were small and generally similar between treatment groups. Few cariprazine-treated patients had PCS changes in lipids or glucose levels. Although mean changes in body weight were small and similar to placebo, the higher percentage of patients with 7% or greater increases in body weight suggest that cariprazine may have been associated with weight gain in a small group of patients in this study. Long-term studies in this patient population are needed to better characterize the effects of cariprazine on body weight. Cariprazine showed no clinically relevant effects on sedation, QT prolongation, or prolactin elevation, issues also commonly encountered with antipsychotic treatments.

Interpretation of study results are limited by the short duration of treatment and lack of an active comparator.

In conclusion, results from this study support the efficacy, safety, and tolerability of cariprazine in patients with acute exacerbation of schizophrenia. Continued research is needed to further establish the benefits of cariprazine in the treatment of schizophrenia; the unique mechanism of action and study results suggest that cariprazine may be an effective new treatment option for schizophrenia.


The authors thank Carol Brown, MS, and Paul Ferguson, MS, of Prescott Medical Communications Group, Chicago, IL, contractors of Forest Research Institute, a subsidiary of Actavis, Inc., for the writing assistance and editorial support for the preparation of this article; and the investigators at each study center: in the United States: Drs Ronald L. Brenner, Barbara A. Burtner, Andro Giorgadze, Ricky S. Mofsen, Henry A. Nasrallah, Anita S. Varma, Stephen J. Volk, and Tram K. Tran-Johnson; in India: Drs Hitendra Gandhi, Venu Jhanwar, Rohan Kusumgar, Dhavale Madhav, B.S.V. Prasad, Nadukuru Raju, and Chudgar Vrajlal; and in South Africa: Dr Juan Paul Schronen.


John M. Kane has consulted with Organon, Eli Lilly, Bristol-Myers Squibb, Intracellular Therapeutics, Boehringer, Rules Based Medicine, AstraZeneca, Otsuka, Novartis, Merck, Myriad, Esai, Pfizer, Lundbeck, J & J, Targacept, Shire, Amgen, Sunovion, Pierre Fabre, Janssen, Alkermes, Jazz, and Forest Laboratories, Inc. He is on the Speakers Bureau for Janssen, Bristol-Myers Squibb, Eli Lilly, and Otsuka and is a shareholder in MedAvante, Inc. Stephen Zukin, Yao Wang, Kaifeng Lu, and Suresh Durgam acknowledge a potential conflict of interest as current or past employees of Forest Research Institute, a subsidiary of Actavis, Inc. Adam Ruth acknowledges a potential conflict of interest as an employee of Prescott Medical Communications Group, a contractor for Forest Research Institute, a subsidiary of Actavis, Inc. Krisztián Nagy and István Laszlovszky acknowledge a potential conflict of interest as current or past employees of Gedeon Richter Plc.


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cariprazine; schizophrenia; antipsychotic; dopamine; receptors; dopamine D3

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