Vraylar (cariprazine) / Mitsubishi Tanabe, Recordati, Gedeon Richter, AbbVie, Hwanin Pharma - LARVOL DELTA

Rational antipsychotic polypharmacy in psychotic and bipolar disorders: A focus on D2 receptor partial agonists. (PubMed, Ment Health Clin) - "Aripiprazole, brexpiprazole, and cariprazine have a unique pharmacology as demonstrated by their high affinity to the dopamine type-2 receptor (ie, D2 receptor). Some partial agonists may be less preferred in particular patient scenarios based on their demonstrated clinical efficacy. Three illustrative patient cases highlight clinical pearls related to the safe and effective use of antipsychotic polypharmacy involving partial agonist antipsychotics."

Journal • Anesthesia • Bipolar Disorder • CNS Disorders • Mood Disorders • Movement Disorders • Psychiatry

RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE) (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: Mayo Clinic

Biomarker • New P4 trial • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Editorial: Enhancing therapeutic strategies: a focus on pharmacovigilance in new wave antidepressants and antipsychotics. (PubMed, Front Psychiatry) - No abstract available

Adverse events • Journal • CNS Disorders

Economic impact of using cariprazine as the first versus subsequent adjunctive therapy for Medicaid beneficiaries with major depressive disorder. (PubMed, J Med Econ) - "MH‑related HRU and costs were also significantly lower. Findings from this real‑world study of Medicaid beneficiaries indicate that earlier cariprazine use is associated with potential reduction in the substantial humanistic and economic burden of MDD."

HEOR • Journal • Reimbursement • Retrospective data • US reimbursement • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Structure-Function Activity Relationships of Cariprazine Analogues with Distinct G Protein versus β-Arrestin Activities at the Dopamine D3 Receptor. (PubMed, ACS Chem Neurosci) - "Moreover, certain substitutions to this aromatic primary pharmacophore appear to confer D3R/D2R functional divergence. These findings offer key mechanistic insights and inform the rational design of next-generation bitopic ligands with optimized signaling properties for the treatment of PSUD and related disorders."

Journal • CNS Disorders • ARRB1

Post-lanosterol inhibition profile based classification of commonly used prescription medications. (PubMed, Transl Psychiatry) - "Using LC-MS/MS we measured 13 post-lanosterol intermediates in control, DHCR7 +/- and DHCR7-/- human dermal fibroblasts exposed to cariprazine, nebivolol, rotigotine, buspirone, lurasidone, fluoxetine, hydroxyzine, amiodarone, spiroxamine, vilazodone and ziprasidone. In addition, DHCR7 +/- fibroblasts responded with greater sterol profile disruptions to all medications, while DHCR7 fibroblasts from patients with Smith-Lemli-Opitz syndrome showed generally a more plateaued response. Knowing the inhibition profile-based classification of medications that have a sterol inhibiting side effect might ultimately translate into safety recommendations during pregnancy and could be critical for new drug development."

Journal • DHCR7

Efficacy and Safety of Cariprazine, Asenapine, Xanomeline-Trospium, and Lumateperone for Acute Exacerbations of Schizophrenia in Adults: A Network Meta-Analysis. (PubMed, Schizophr Bull Open) - "However, further head-to-head comparisons with standard treatments are needed to guide a more evidence-based selection. Future trials with longer durations and more diverse populations are warranted to confirm and extend these findings."

Journal • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

Testing the dopamine D3 receptor partial-agonist in Opioid Use Disorder (OUD) (Neuroscience 2025) - "Grant Support NIH/NIDA UG1DA050209 Clinical Laboratories with Integrated Neuroscience (Kampman and Childress MPI) AIM: Philadelphia has the third highest rate of opioid overdose deaths in the country, with fentanyl present in 82% of fatal opioid overdoses, and in nearly half of cocaine overdoses...As D3-specific agents for humans are still in development, we have begun testing cariprazine (CRZ), a commercially-available medication with high D3 (vs. D2) affinity, for clinical, brain and behavioral impacts in individuals with Opioid Use Disorder. We are conducting a phase IIa, randomized, single-blind, placebo-controlled pilot study (8 outpatient weeks; twice weekly urines; n=25, ongoing) of low-dose CRZ (1.5mg/d) vs. placebo (PBO) in OUD outpatients who are already taking a stable dose of either methadone or buprenorphine... This preliminary analysis of retention and drug use outcomes for 1.5 mg CRZ in OUD did not detect group differences. However, as clinical outcomes..."

Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse

Dopamine D3 Receptor Mediated Action in Hippocampus CA1 (Neuroscience 2025) - "While D2R antagonism has not been successful in treating cognitive symptoms, the new antipsychotic cariprazine functioning as a D3R partial agonist has shown some signs of cognitive symptom relief...This demonstrates diverse D3R-mediated modulation of hippocampus CA1 circuitry. Future experiments will focus on examining the D3R-mediated effects of different antipsychotics on CA1 function."

CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • DRD2

LY379268 and cariprazine but not donepezil differentially recover alterations in spontaneous oscillations, gamma-band auditory steady-state response and MMN caused by MK-801 in a rat EEG study: relevance for schizophrenia drug development (Neuroscience 2025) - "Their effects on MMN are also described. These results highlight glutamatergic as well as dopaminergic and serotoninergic systems as interesting targets to recover cortical excitation/inhibition balance in SZ."

Late-breaking abstract • Preclinical • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Trajectories and predictors of depressive and anxiety symptom improvement with adjunctive cariprazine in antidepressant-treated adults with major depression: A Bayesian mega-analysis of two randomized trials. (PubMed, J Affect Disord) - "This mega-analysis highlights how variability in symptom trajectories with adjunctive cariprazine can be leveraged clinically to understand differences in response. These findings support using early symptom change and individual patient characteristics to inform clinical decision-making and tailor adjunctive treatment strategies."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Cost-Effectiveness Analysis of Cariprazine vs. Risperidone for the Treatment of Schizophrenia With Predominantly Negative Symptoms (PNS) in United Arab Emirates (ISPOR-EU 2025) - "Cariprazine is a dominant option for the treatment of schizophrenia with PNS in one of UAE's major psychiatric hospitals. Our findings may support its inclusion in the hospital formulary."

Cost effectiveness • HEOR • CNS Disorders • Psychiatry • Schizophrenia

Distinct functional profiles of partial agonist antipsychotics in cAMP and β-arrestin signaling mechanisms of dopamine D2 and D3 receptors in vitro. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "While cariprazine showed partial agonism and partial antagonism at D3 receptor-mediated β-arrestin translocation, aripiprazole and brexpiprazole displayed only weak or no agonist but potent antagonist activity. These data suggest differentiated mechanism of action of cariprazine at the D3 receptor signaling compared to aripiprazole and brexpiprazole."

Journal • Preclinical • CNS Disorders

Impact of selected second and third generation antipsychotics on cognitive dysfunction in schizophrenia-spectrum disorders. Systematic review and network meta-analysis. (PubMed, Int Clin Psychopharmacol) - "This study aimed to: (a) systematically review randomized controlled trials (RCTs) evaluating the cognitive effects of third-generation antipsychotics (TGAs: brexpiprazole, cariprazine, lumateperone, and lurasidone) and xanomeline-trospium; and (b) perform a network meta-analysis (NMA) including additional second-generation antipsychotics with potential procognitive effects. A systematic literature search identified eligible RCTs, which were combined with trials on aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone from a previous meta-analysis...In conclusion, selected second and TGAs, including M1/M4 receptor agonists such as xanomeline, may offer promising treatment options for cognitive dysfunction. Further research should personalize pharmacological strategies based on cognitive profiles."

Journal • Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Cariprazine in the Treatment of Pediatric Patients With Irritability Associated With ASD: A Randomized Controlled Trial (AACAP 2025) - "Pediatric patients with ASD treated with cariprazine had a statistically significant, greater improvement in irritability based on both caregiver- and clinician-reported scales compared with placebo, suggesting a potentially positive benefit-risk profile for cariprazine in this population.ASD, APS, RCT"

Clinical • Mood Disorders • Pediatrics • Psychiatry

Long-Term Safety of Cariprazine in Pediatric Patients With Schizophrenia, Bipolar I Disorder, or ASD: Interim Results From an Open-Label Study (AACAP 2025) - "This study includes a robust representation of pediatric psychiatry patients across indications, age groups, and demographics, supporting data generalizability. CAR treatment in pediatric patients was safe and generally well-tolerated, with AEs and laboratory findings generally consistent with the established safety profile in adults; no new safety concerns were identified.ASD, DDD, BRD"

Clinical • Bipolar Disorder • CNS Disorders • Fatigue • Pediatrics • Psychiatry • Schizophrenia

Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder (clinicaltrials.gov) - P3 | N=310 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion • Autism Spectrum Disorder • Bipolar Disorder • CNS Disorders • Genetic Disorders • Pediatrics • Psychiatry • Schizophrenia

Valbenazine for the Treatment of Chronic Motor or Vocal Tic Disorder (CMVTD). (PubMed, Cureus) - "The present report describes a pediatric patient with CMVTD who had previously failed multiple pharmacological treatments, including two Food and Drug Administration (FDA)-approved agents (pimozide, aripiprazole), guanfacine, psychotherapy, and novel compounds (lumateperone, cariprazine). This case illustrates a marked therapeutic response to valbenazine in a patient with CMVTD refractory to conventional and novel therapies. These observations highlight the potential role of vesicular monoamine transporter 2 (VMAT2) inhibition in tic disorders and also the need for further clinical study."

Journal • CNS Disorders • Otorhinolaryngology • Pediatrics • Psychiatry • Tic Disorders • Tourette Syndrome

Dopamine D3 Receptor Occupancy in Bipolar Depression (clinicaltrials.gov) - P4 | N=8 | Not yet recruiting | Sponsor: New York State Psychiatric Institute | Trial completion date: Dec 2026 ➔ May 2027 | Trial primary completion date: Dec 2026 ➔ May 2027

Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Therapeutic potential of saffron for negative and cognitive symptoms in schizophrenia: clinical and preclinical insights (ECNP 2025) - "While recent agents (i.e., cariprazine, muscarinic receptor agonists, glutamate modulators, and pimavanserin) have shown partial promise, consistent benefits for negative and cognitive domains remain elusive...Results One randomized controlled trial (RCT) (2) evaluated adjunctive saffron (15 mg every 12 hours for 8 weeks) in 26 patients with chronic schizophrenia receiving risperidone, compared to 24 patients receiving risperidone and placebo...Three preclinical studies used rodent models of schizophrenia-like symptoms induced by MK-801 (a non-competitive NMDA receptor antagonist) (3), ketamine (4), or apomorphine-induced (5) models...Although the precise mode of action in humans remains to be fully elucidated, saffron's favorable tolerability profile and potential benefits on metabolic dysfunction support further investigation into its role in alleviating negative symptoms of schizophrenia. Larger, well-controlled trials are warranted to replicate these findings,..."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • SIRT1

Post-discharge engagement in early psychosis: a retrospective analysis of adherence patterns after first psychiatric admission (ECNP 2025) - "Pharmacological treatment with olanzapine (p = 0.017) and cariprazine (p = 0.001) was also associated with better adherence. In this clinical sample, the presence of complex hallucinations, disorganised thought or speech, and aggressive behaviour were significant predictors of lower adherence to follow-up care after FEP. These clinical features should be prioritised in post-discharge planning and monitoring strategies to support continued engagement and optimise outcomes."

Adherence • Retrospective data • CNS Disorders • Psychiatry

Beyond guidelines: the challenge of routine clinical practice in OCD, report of a clinical case (ECNP 2025) - "During follow-up, sertraline was prescribed up to 100 mg per day without notable clinical improvement...A therapeutic alliance was established, and fluvoxamine 100 mg per day was prescribed, with no significant clinical response. An augmentation with aripiprazole was then proposed; the patient preferred monotherapy and agreed to switch treatment (up to 15 mg per day), resulting in partial symptom improvement but also the development of limiting akathisia...While SSRIs and cognitive-behavioral therapy remain the mainstays of treatment, pharmacological augmentation with atypical antipsychotics can be a valuable strategy in resistant cases. This case underscores the potential efficacy of atypical antipsychotics, such as cariprazine, as monotherapy in OCD, highlighting the importance of personalized treatment plans to optimize long-term outcomes."

Clinical • CNS Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Pharmacological strategies targeting negative symptoms in schizophrenia (ECNP 2025) - "In a 14-week RCT versus risperidone (n = 460), it achieved a 2.6 point greater reduction on the PANSS Negative subscale (p<0.001) and improved social functioning [4]. Low-dose amisulpride and lurasidone have shown moderate benefits, particularly when negative symptoms are secondary to depression or extrapyramidal effects...Cholinergic modulation with xanomeline–trospium recently showed significant reductions in both positive and negative symptoms in a phase II trial (n = 182), suggesting a novel non-dopaminergic approach. Antidepressant augmentation (primarily SSRIs and mirtazapine) produced modest additional benefits, though heterogeneity across studies tempers confidence [5]... Emerging pharmacotherapies targeting dopamine D3 receptors, serotonergic modulation and glutamatergic pathways offer promising avenues for alleviating negative symptoms in schizophrenia. Cariprazine and roluperidone have demonstrated the most robust RCT evidence, memantine is a viable adjunct..."

CNS Disorders • Depression • Psychiatry • Schizophrenia

Measurement of the Personal and Social Performance (PSP) Scale in patients treated with antipsychotics (ECNP 2025) - "Next in line were Ziprasidone (63.0), monthly Paliperidone (61.3), oral Olanzapine (60.9), total Paliperidone use (56.2), three-month Paliperidone (55.3), Risperidone (54.5), and six-month Paliperidone (50.7). At the lower end of our data, Clozapine showed the lowest PSP scores, with an average of 48.7 points... The results suggest that third-generation antipsychotics are associated with better functionality, as measured by the PSP Scale, compared to second-generation antipsychotics. This difference may reflect a more favorable profile of third-generation antipsychotics, with fewer sedative and metabolic side effects, which could contribute to improved quality of life and functioning in patients. It is also important to consider the individual response of patients and adherence to treatment.These findings reinforce our understanding of the superiority of partial agonists such as Aripiprazole and Cariprazine over dopamine antagonists in preserving and restoring patient..."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

A long-term follow-up examining the safety, efficacy, and tolerability of cariprazine as an adjunct in adults with attention-deficit/hyperactivity disorder (ECNP 2025) - "Furthermore, cariprazine appeared to enhance cognitive functioning by improving working and episodic memory and response inhibition. Finally, a 2-year follow-up analysis of ADHD symptomatology, cognition, hedonic tone, energy, and motivation will be completed to determine the long-term efficacy of adjunctive cariprazine treatment in patients with complex and severe ADHD."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry