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

AbbVie Beats on Q2 Earnings & Sales, Stock Up on Raised '25 EPS View (Yahoo Finance) - "Sales from the neuroscience portfolio increased 24% to $2.68 billion, driven by higher sales of Botox Therapeutic, depression drug Vraylar and migraine drugs Ubrelvy and Qulipta. Neuroscience sales beat the Zacks Consensus Estimate and our model estimate of $2.47 billion and $2.48 billion, respectively. While Botox Therapeutic sales rose 14.2% to $928 million, sales of Vraylar increased 16.3% to $900 million. Sales of Ubrelvy totaled $338 million, up 47.2%. Qulipta sales increased 76.9% to $267 million. Sales of Vyalev, the recently approved transformative therapy for advanced Parkinson’s disease, totaled $98 million, compared with $63 million in the first quarter."

Sales • Depression • Migraine • Pain • Parkinson's Disease

Transdiagnostic Efficacy of Cariprazine: A Systematic Review and Meta-Analysis of Efficacy Across Ten Symptom Domains. (PubMed, Pharmaceuticals (Basel)) - "Previous reports of cariprazine's anti-craving and anti-abuse effects come from real-world evidence rather than RCT data. Cariprazine appears to be promising in addressing a broad range of symptom domains across psychiatric conditions."

Journal • Retrospective data • Review • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Mood Disorders • Psychiatry

Dopamine Partial Agonists in Pregnancy and Lactation: A Systematic Review. (PubMed, Pharmaceuticals (Basel)) - "Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia spectrum and mood disorders. There were serious concerns about the use of dopamine D2/D3 partial agonists during lactation. The use of dopamine partial agonists during pregnancy appears to be safe, but during breastfeeding they should be better avoided."

Journal • Review • CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

Exploring the Therapeutic Potential of Ar-tur in Alzheimer Disease: A Cheminformatics, Pharmacokinetics, and System Pharmacology Approach. (PubMed, ACS Chem Neurosci) - "Molecular docking of DRs with dopamine, cariprazine, brexpiprazole, RO-10-5824, CP226269, and donepezil connotes that Ar-tur behaves like an agonist of DR2 and DR4 by binding to the active site residues like the dopamine and DR agonists. This is the first report stating the impressive drug-like properties of Ar-tur and holds the potential to rescue the vulnerable dopaminergic system by regulating DRs."

Journal • PK/PD data • Alzheimer's Disease • CNS Disorders

Effects of adjunctive cariprazine formulary restrictions in major depressive disorder. (PubMed, Am J Manag Care) - "Patients with MDD who had an initial adjunctive cariprazine claim rejected for a formulary-related reason and subsequently received an atypical antipsychotic experienced significantly higher hospitalization rates than those with approved initial cariprazine claims, suggesting that formulary restrictions on adjunctive cariprazine may be associated with negative downstream effects."

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

Investigating Psychopharmaceutical Effects on Early Vertebrate Development Using a Zebrafish Model System. (PubMed, J Dev Biol) - "Exposure to cariprazine, aripiprazole, trazodone, and AY9944 increased 7-dehydrocholesterol levels compared to vehicle-treated zebrafish. Significant differences in disease-associated gene expression, brain structure, and functional behaviors were observed in psychopharmaceutical and AY9944-treated zebrafish compared to controls. These data reveal that the high-throughput zebrafish model system can discern psychopharmaceutical effects on cholesterol synthesis, gene transcription, and key features of early vertebrate development that influences behavior."

Journal • Developmental Disorders

Cariprazine & Clozapine: A systematic review of a promising antipsychotic combination for treatment-resistant schizophrenia. (PubMed, Int J Neuropsychopharmacol) - "Overall, the combination appears safe and promising, especially for persistent negative symptoms, likely due to complementary neuroreceptor effects. Larger controlled trials are needed to confirm these findings."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Expert Guidelines on the Use of Cariprazine in Bipolar I Disorder: Consensus from Southeast Asia. (PubMed, Healthcare (Basel)) - "Cariprazine was also considered suitable as first-line therapy, including for first-episode bipolar depression (Mdn: 8, IQR: 7-9) and first-episode mania (Mdn: 8; IQR: 8-9). The consensus recommendations may serve as practical guidance for clinicians to make informed decisions regarding the management of adult patients with BP1D, while considering the preferences and circumstances of individual patients."

Journal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Prescription pattern and medical expenses in executive psychiatric clinic - RSUD Dr. Chasbullah Abdulmadjid (Type B government hospital) Bekasi City Indonesia - period March – November 2024 (CINP-AsCNP 2025) - "The most commonly prescribed medications were antidepressants (Vortioxetine, Escitalopram, Fluvoxamine, Mirtazapine, Duloxetine), antipsychotics (Brexpiprazole, Cariprazine, Aripiprazole, Quetiapine IR, Sulpiride) and non-benzodiazepines (Lemborexant). The coverage expenses for Psychiatric Clinic Type B Hospital with Indonesian national health insurance using Indonesia Case Base Groups (INA-CBGs) per month is 196.100 IDR / 12 USD / 20 AUD for consultation and medications (7 days to hospital) and the rest 23 days is fee for service. In comparison, the expenses at Executive Psychiatric Clinic Type B Government Hospital Bekasi City Indonesia are five times higher than national health insurance could cover to the hospital. And indeed each payment system has its own advantages and disadvantages."

Clinical • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Schizophrenia • Sleep Disorder

Neuroleptic malignant syndrome in a patient with COVID-19 and the possible role of SARS-CoV-2 in its manifestation: case report and overview of published cases. (PubMed, BMC Psychiatry) - "As SARS-CoV-2 is known to interact with angiotensin-converting enzyme 2 and DOPA-decarboxylase is known to be coexpressed with this receptor, we hypothesized that COVID-19 infection might play a substantial role in the development of NMS."

Journal • CNS Disorders • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Psychiatry • Respiratory Diseases • Schizophrenia

Adverse events associated with four atypical antipsychotics used as augmentation treatment for major depressive disorder: A pharmacovigilance study based on the FAERS database. (PubMed, J Affect Disord) - "It is suggesting a potential increased risk of various ADEs in patients with MDD when taking AAPs. The causal relationship and the exact mechanism between drugs and ADEs remains unclear, requiring further research."

Adverse events • Journal • Cardiovascular • CNS Disorders • Depression • Glaucoma • Inflammation • Major Depressive Disorder • Mental Retardation • Metabolic Disorders • Mood Disorders • Movement Disorders • Obsessive-Compulsive Disorder • Ophthalmology • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Real-world effectiveness of cariprazine in major depressive disorder and bipolar I disorder in the United States. (PubMed, J Med Econ) - "Greater improvements were observed in the sensitivity analysis. This real-world effectiveness study of cariprazine treatment for MDD (adjunctive use) or BP-I demonstrated clinically meaningful and sustained improvement in depression symptoms during short- and long-term follow-up."

Journal • Real-world evidence • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Comparative Efficacy, Safety, and Tolerability of Xanomeline and Trospium Chloride versus Eight Atypical Antipsychotics for the Acute Treatment of Adults with Schizophrenia - A Network Meta-Analysis (ISPOR 2025) - " Xanomeline/trospium treatment significantly improved odds of clinical response versus aripiprazole (odds ratio [OR]: 1.85; 95% credible interval [CrI]: 1.11, 3.11), brexipiprazole (OR: 2.23; 95% CrI: 1.34, 3.83), and cariprazine (OR: 2.05; 95% CrI: 1.19, 3.57), increased odds of all-cause discontinuation versus all comparators except cariprazine, and reduced odds of clinically significant weight gain versus aripiprazole, brexipiprazole, cariprazine, lumateperone, olanzapine, quetiapine, and risperidone. Xanomeline/trospium demonstrated improved clinical response and reduced weight gain compared with several existing oral antipsychotics."

Retrospective data • Anesthesia • CNS Disorders • Psychiatry • Schizophrenia

The Synergistic Effect of High-Frequency Rtms With Atypical Antipsychotics on the Alleviation of Negative Symptoms of Schizophrenia (APA 2025) - "A further comparison of SANS scores between the medications used showed that paliperidone and cariprazine were similarly efficacious, both being better than aripiprazole and lurasidone (p<0.001). Conclusions Significant reduction of SANS total score and specifically in the avolition (22%) and alogia (19%) domains. It is noteworthy that individuals who were using paliperidone and cariprazine showed significantly better outcomes in terms of negative symptom reduction."

CNS Disorders • Psychiatry • Schizophrenia

Heads Up: A Potential Interplay Between Antipsychotic Medications Sickle Cell Trait and Priapism (APA 2025) - "He experienced priapism with aripiprazole, risperidone, paliperidone, olanzapine, and lurasidone. Despite switching to cariprazine, which has lower alpha-1 adrenergic antagonism, episodes of priapism persisted. The patient achieved partial psychiatric stabilization with a low dose of pimozide and valproate, and sildenafil was added as a preventive measure for priapism, resulting in no further episodes. Pimavanserin was not pursued due to its cost... Clinicians should be aware of this potential side effect and educate patients on the importance of reporting symptoms and seeking timely medical care. Further research is needed to clarify the mechanisms of priapism related to antipsychotic use, develop treatment protocols for managing psychosis in cases of recurrent priapism, and explore the relationship between sickle cell trait and antipsychotic-induced priapism."

Cardiovascular • CNS Disorders • Genetic Disorders • Hematological Disorders • Psychiatry • Schizophrenia • Sickle Cell Disease

Unsupervised Graph Clustering Reveals a Clinical Taxonomy of Antipsychotics (APA 2025) - "Cluster 1 contained Aripiprazole, Brexpiprazole, Cariprazine, Lurasidone, Sertindole, and Ziprasidone, and was characterized by an excellent side-effect profile but also with the lowest efficacy. Cluster 2 contained Chlorpromazine, Haloperidol, Loxapine, Molindone, Perphenazine, and Thiothixene, and showed strong efficacy in positive symptoms, but also had a high-risk for EPS, QTc prolongation and seizures. Cluster 3 contained Clozapine, Iloperidone, Olanzapine, Quetiapine, Thioridazine, and Zotepine, and showed strong overall efficacy but carried the highest risk for sedation and metabolic side effects. Cluster 4 contained Amisulpride, Asenapine, Paliperidone, Risperidone, and Sulpride, and showed excellent positive and negative symptom efficacy but carried the highest risk of hyperprolactinemia. Cluster 5 contained Flupentixol, Fluphenazine, Pimozide, and Trifluoperazine and showed the lowest efficacy with a high risk of causing EPS. Conclusion Despite traditional..."

Clinical • Anesthesia • CNS Disorders • Epilepsy • Hypotension • Psychiatry • Schizophrenia

Cariprazine for Comorbid Cocaine and Opioid Use Disorder (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Kyle Kampman | Trial primary completion date: Apr 2025 ➔ Dec 2025

Trial primary completion date • Substance Abuse

SMART-BD: Sequential Multiple Assignment Randomized Trial for Bipolar Depression (clinicaltrials.gov) - P4 | N=2726 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Efficacy of Adjunctive Cariprazine on Anxiety Symptoms in Patients With Major Depressive Disorder: Post Hoc Analysis of a Randomized Placebo-Controlled Trial. (PubMed, J Clin Psychiatry) - P3 | "Similar trends were observed for adjunctive cariprazine 1.5 mg/d in subgroups of patients with elevated anxiety symptoms. In addition to reducing depressive symptoms, adjunctive cariprazine may also reduce anxiety symptoms in patients with MDD, regardless of the level of baseline anxiety."

Clinical • Journal • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

The effect of adjunctive cariprazine on symptoms of anhedonia in patients with major depressive disorder. (PubMed, J Affect Disord) - P3 | "In patients with MDD and moderate-to-severe anhedonia, adjunctive cariprazine improved symptoms of general depression and anhedonia, suggesting a potential benefit for patients with this clinically significant symptom."

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

AbbVie Reports First-Quarter 2025 Financial Results (PRNewswire) - "Global net revenues from the neuroscience portfolio were $2.282 billion, an increase of 16.1 percent on a reported basis, or 17.0 percent on an operational basis. Global Vraylar net revenues were $765 million, an increase of 10.3 percent. Global Botox Therapeutic net revenues were $866 million, an increase of 15.8 percent on a reported basis, or 17.0 percent on an operational basis. Global Ubrelvy net revenues were $240 million, an increase of 17.8 percent on a reported basis, or 18.0 percent on an operational basis. Global Qulipta net revenues were $193 million, an increase of 47.6 percent on a reported basis, or 48.3 percent on an operational basis."

Sales • Bipolar Disorder • Major Depressive Disorder • Migraine • Pain • Schizophrenia

Effect of ponatinib on the metabolism of cariprazine in vitro and in vivo and the underlying mechanism. (PubMed, Toxicol Appl Pharmacol) - "The objective of the present study was to examine the inhibitory impacts of three antitumor drugs (olmutinib, napabucasin and ponatinib) on the metabolism of cariprazine, and the molecular docking of cariprazine and ponatinib in relation to CYP3A4 was also evaluated. Molecular docking studies had demonstrated that both cariprazine and ponatinib could engage in hydrophobic interactions with residue PHE-304 on CYP3A4. Consequently, when ponatinib is employed in conjunction with cariprazine in a clinical setting, it is imperative to assess the efficacy and adverse effects, and adjust the dosage to attain the optimal efficacy."

Journal • Preclinical • CNS Disorders • Mental Retardation • Oncology • Psychiatry • Schizophrenia • CYP3A4

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

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

The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis. (PubMed, BMC Psychiatry) - "Holistically considering each endpoint and corresponding "time window", certain SGAs appeared to be efficient augmentation to anti-depressants for TRD, but aripiprazole was relatively more effective and better tolerated."

Clinical • Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

ESG-1-60 and ESG-1-61: Novel dopamine D3 receptor-preferring partial agonists/antagonists that inhibit cocaine taking and seeking in rodents. (PubMed, Br J Pharmacol) - "Novel D3 receptor-preferring compounds ESG-1-60 and ESG-1-61 were highly effective in reducing cocaine-taking and cocaine-seeking, under various reinforcement conditions. ESG-1-60 warrants further investigation as a new pharmacotherapy for treating cocaine use disorder as it is effective in these models and lacks unwanted behavioural effects."

Journal • Preclinical