Lodopin (zotepine) / Astellas - LARVOL DELTA

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

Improvement in Quality of Seizures in Electroconvulsive Therapy With Zotepine: A Case Report. (PubMed, J ECT) - "ECT was resumed in March 2023 and accompanied by risperidone (RIS) 4 mg, with SQC scores of 1-2 points for sessions 1-8. ECT was terminated in September 2023 (after 27 sessions in total) when the patient was mentally ready to be released from isolation. This case indicates that ZTP may improve the quality of ECT-induced seizures."

Journal • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry • Schizophrenia

Drug-induced megacolon in schizophrenia: a pharmacovigilance study of antipsychotic medications from the Japanese Adverse drug Event Database: a disproportionality analysis. (PubMed, Expert Opin Drug Saf) - "Zotepine, sulpiride, and quetiapine are associated with antipsychotic-induced megacolon in schizophrenia patients, and it is suggested that there is a gender difference. This study provides novel evidence for evaluating adverse drug events related to schizophrenia pharmacotherapy, contributing to improved quality of life for these patients."

Adverse events • Journal • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Psychiatry • Schizophrenia

Blockade of Voltage-Gated K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells by the Antipsychotic Drug Zotepine. (PubMed, J Appl Toxicol) - "Zotepine also induced membrane depolarization. These results indicate that zotepine inhibits Kv currents (mainly Kv1.5 subtype) in dose-, time-, and use (state)-dependent manners by changing the steady-state inactivation curve."

Journal • Preclinical • Cardiovascular • CNS Disorders • Diabetes

Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HT2A Receptors. (PubMed, Molecules) - "The crystal structure of 5HT2A/zotepine (antagonist) (PDB: 6A94) was used to set up the simulation systems in a lipid bilayer environment...These structural changes were transmitted to the intracellular ends of TM5, TM6, and ICL3, resulting in the breaking of the ionic lock and subsequent G protein activation. The studies could be helpful in future design of selective agonists/antagonists for various serotonin receptors (5HT1A, 5HT2A, 5HT2B, 5HT2C, and 5HT7) involved in detrimental disorders, such as addiction and schizophrenia."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Association of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine versus patients treated with olanzapine, risperidone, or quetiapine: A systematic review and meta-analysis. (PubMed, Schizophr Res) - "In patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs."

Journal • Retrospective data • Review • CNS Disorders • Diabetes • Metabolic Disorders • Psychiatry • Schizophrenia

Living Systematic Review and Meta-Analysis of Pharmacokinetic Drug-Gene Interactions in Schizophrenia Pharmacotherapy: The Importance of CYP450 Genetic Polymorphism (SIRS 2024) - "This will include interactions of: Aripiprazole with CYP3A4/5; Asenapine with CYP1A2 and UGT1A4; Clozapine with CYP2D6, CYP1A2 and CYP3A4/5; Iloperidone with CYP3A4/5 and CYP2D6; Olanzapine with UGT1A4 and CYP1A2; Quetiapine with CYP3A4/5; Risperidone with CYP3A4/5; Zotepine with CYP3A4/5 and CYP1A2; Haloperidol with CYP3A4/5, UGT2B7 and CYP1A2; Chlorpromazine with CYP1A2, CYP3A4 or CYP2D6; and Zuclopenthixol with CYP3A4/5 and CYP2D6. As this abstract describes the proposed protocol for the living systematic review and meta-analysis, no results are available at the time. This living systematic review and meta-analysis will aim to encompass all clinically relevant antipsychotic drugs that are metabolized by at least one liver enzyme that is coded by the polymorphic gene. This way, the comprehensive database of pharmacokinetic drug-gene interactions relevant for the schizophrenia therapy will be created."

PK/PD data • Retrospective data • Review • CNS Disorders • Schizophrenia • CYP1A2 • CYP2C19 • CYP2D6 • CYP3A4

Basic and Clinical Research Based on Clinical Questions:Reduction of Antipsychotic Medication-induced Adverse Events (PubMed, Yakugaku Zasshi) - "A national multicenter prospective observational study of 631 newly initiated patients showed that initiation of clozapine and zotepine treatment significantly increased the incidence of hyperglycemia. In addition, obesity has been shown to significantly increase the incidence of antipsychotic-induced hyperglycemia. Because these studies were conducted to resolve questions that arose in actual clinical practice, the study results obtained are considered to have clinical applicability."

Adverse events • Journal • CNS Disorders • Diabetes • Genetic Disorders • Obesity

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period: Retrospective cohort study. (PubMed, Neuropsychopharmacol Rep) - "Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic-induced constipation."

Journal • Retrospective data • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Psychiatry • Schizophrenia

Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis. (PubMed, Mol Psychiatry) - "Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d...There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine...In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS."

Adverse events • Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • DRD2

Long-term efficacy of antipsychotic drugs in initially acutely ill adults with schizophrenia: systematic review and network meta-analysis. (PubMed, World Psychiatry) - "In terms of overall symptoms, olanzapine was on average more efficacious than ziprasidone (standardized mean difference, SMD=0.37, 95% CI: 0.26-0.49), asenapine (SMD=0.33, 95% CI: 0.21-0.45), iloperidone (SMD=0.32, 95% CI: 0.15-0.49), paliperidone (SMD=0.28, 95% CI: 0.11-0.44), haloperidol (SMD=0.27, 95% CI: 0.14-0.39), quetiapine (SMD=0.25, 95% CI: 0.12-0.38), aripiprazole (SMD=0.16, 95% CI: 0.04-0.28) and risperidone (SMD=0.12, 95% CI: 0.03-0.21)...The differences between olanzapine and lurasidone, amisulpride, perphenazine, clozapine and zotepine were either small or uncertain...Concerning weight gain, the impact of olanzapine was higher than all other antipsychotics, with a mean difference ranging from -4.58 kg (95% CI: -5.33 to -3.83) compared to ziprasidone to -2.30 kg (95% CI: -3.35 to -1.25) compared to amisulpride. Our data suggest that olanzapine is more efficacious than a number of other antipsychotic drugs in the longer term, but its efficacy must be weighed..."

Journal • Retrospective data • Review • Anesthesia • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • PRL

Antipsychotic-induced akathisia in adults with acute schizophrenia: A systematic review and dose-response meta-analysis. (PubMed, Eur Neuropsychopharmacol) - "We obtained data on all antipsychotics except clozapine and zotepine. In patients with acute exacerbations of chronic schizophrenia, from moderate to high certainty of evidence, our analysis showed that sertindole and quetiapine carried negligible risks for akathisia across examined doses (flat curves), while most of the other antipsychotics had their risks increase initially with increasing doses and then either plateaued (hyperbolic curves) or continued to rise (monotonic curves), with maximum ORs ranging from 1.76 with 95% Confidence Intervals [1.24, 2.52] for risperidone at 5.4 mg/day to OR 11.92 [5.18, 27.43] for lurasidone at 240 mg/day...In conclusion, liability of akathisia varies between antipsychotics and is dose-related. The dose-response curves for akathisia in most antipsychotics are either monotonic or hyperbolic, indicating that higher doses carry a greater or equal risk compared to lower doses."

Journal • Retrospective data • Review • CNS Disorders • Movement Disorders • Psychiatry • Schizophrenia

Effect of antipsychotic use by patients with schizophrenia on deceleration capacity and its relation to the corrected QT interval. (PubMed, Gen Hosp Psychiatry) - "Assessing DC could facilitate monitoring and identification of increased risk of cardiac mortality in patients with schizophrenia that take antipsychotics. Assessing both DC and the QTc may enhance the accuracy of predicting sudden cardiac death."

Journal • Cardiovascular • CNS Disorders • Psychiatry • Schizophrenia

Onset of Action of Selected Second-Generation Antipsychotics (Pines)-A Systematic Review and Meta-Analyses. (PubMed, Biomedicines) - "The objective of this review was to estimate time to onset of action and time to maximum antipsychotic effect of asenapine, olanzapine, quetiapine, and zotepine (pines). The summarized effect across all included pines administered as immediate-release formulations showed a statistically significant effect at week 1 (SMD, -0.20 [CI95% -0.28, -0.13]), which increased until week 3 (SMD, -0.42 [CI95% -0.50, -0.34]), after which the effect leveled off (week 6: SMD, -0.53 [CI95% -0.62, -0.44]). The sensitivity analyses of the individual pines confirm this finding, although data sparsity increases variability and limits conclusiveness of these analyses."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Metabolic side effects in persons with schizophrenia during mid- to long-term treatment with antipsychotics: a network meta-analysis of randomized controlled trials. (PubMed, World Psychiatry) - "Chlorpromazine produced the most weight gain (mean difference to placebo: 5.13 kg, 95% credible interval, CrI: 1.98 to 8.30), followed by clozapine (4.21 kg, 95% CrI: 3.03 to 5.42), olanzapine (3.82 kg, 95% CrI: 3.15 to 4.50), and zotepine (3.87 kg, 95% CrI: 2.14 to 5.58). In conclusion, antipsychotic drugs differ in their propensity to induce metabolic side effects in mid- to long-term treatment. Given that schizophrenia is often a chronic disorder, these findings should be given more consideration than short-term data in drug choice."

Adverse events • Journal • Retrospective data • CNS Disorders • Dyslipidemia • Psychiatry • Schizophrenia

A new serotonin 2A receptor antagonist with potential benefits in non-alcoholic fatty liver disease. (PubMed, Life Sci) - "The in silico protocol compares SJT4a with four known 5-HT2AR ligands with different activities (LSD, methiothepin, zotepine, risperidone). In our tests, SJT4a showed intense activity in diminishing the most relevant hallmarks of NASH in the DIO-NASH mice model. We proposed a possible mode of action for SJT4a based on its 5-HT2AR antagonist activity."

Journal • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

The relation between second-generation antipsychotics and laxative use in elderly patients with schizophrenia. (PubMed, Psychogeriatrics) - "Laxative use is common in elderly schizophrenia patients treated with SGAs. In cases of clinically significant constipation, switching to an SGA with a lower risk for constipation, or discontinuing the use of mood stabilisers should be considered, if clinically feasible."

Journal • CNS Disorders • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Psychiatry • Schizophrenia

Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics. (PubMed, Pharmaceutics) - "In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration."

Journal • PK/PD data • CNS Disorders • Hematological Disorders • Immunology • Inflammation • Psychiatry • Schizophrenia

Individual-Patient-Data (IPD) Meta-Analysis of the Efficacy of Clozapine versus Other Second-Generation Antipsychotic Drugs in Patients with Treatment-Resistant Schizophrenia (SIRS 2022) - "We identified 18 eligible trials with 1613 participants comparing clozapine to olanzapine, risperidone, ziprasidone, zotepine, haloperidol (as active comparator) or SGAs as a group. For 12 studies (1089 participants) IPD-data is available, for 6 studies (524 participants) aggregate data is available. Currently, we extract the relevant data and harmonize the IPD-datasets for analysis."

Retrospective data • CNS Disorders • Schizophrenia • Schizophreniform Disorder

Development of Solid Self Emulsifying Systems (SSES) of Zotepine with Enhanced Bioavailability Potential: Effect of discrete Adsorbents (ACS-Sp 2022) - "in vivo studies, SSES showed the bioavailability of two .26 folds above the pure zotepine suspension. of these results from SSES show their potential to enhance the oral bioavailability of zotepine."

Increase in Dissolution Rate of Zotepine via Nanomilling Process - Impact of Dried Nanocrystalline Suspensions on Bioavailability. (PubMed, AAPS PharmSciTech) - "Accelerated stability studies of the optimized lyophilized formulation at 40°C and 75% RH suggested stability of the nanocrystals for at least a 6-month period. The obtained nanocrystals successfully showed dissolution enhancement and improved oral bioavailability of poorly water-soluble drug, zotepine."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Effects of an Atypical Antipsychotic, Zotepine, on Astroglial L-Glutamate Release through Hemichannels: Exploring the Mechanism of Mood-Stabilising Antipsychotic Actions and Antipsychotic-Induced Convulsion. (PubMed, Pharmaceuticals (Basel)) - "These results suggest that ZTP enhances astroglial L-glutamate release in a concentration-dependent and time-dependent manner due to the enhanced function of astroglial hemichannels, probably via activation of Akt signalling. Therefore, the enhanced astroglial L-glutamatergic transmission induced by ZTP is, at least partially, involved in the mood-stabilising antipsychotic and proconvulsive actions of ZTP."

Journal • CNS Disorders • Epilepsy • Mental Retardation • Psychiatry • Schizophrenia • GJA1

The type rather than the daily dose or number of antipsychotics affects the incidence of hyperglycemic progression. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "We found that treatment with zotepine and clozapine was associated with a significantly high incidence of hyperglycemic progression. Furthermore, changes in HbA1c levels 6 mo after the initiation of zotepine treatment were significantly higher than those following blonanserin and haloperidol treatments...Our study indicated that the type of antipsychotic had a greater affect on the incidence of hyperglycemic progression than the daily dose of antipsychotics or their number. Among these, zotepine was most likely to increase the incidence of hyperglycemic progression, suggesting the need for caution when these antipsychotics are prescribed."

Journal • CNS Disorders • Diabetes • Psychiatry • Schizophrenia

Prolactin levels influenced by antipsychotic drugs in schizophrenia: A systematic review and network meta-analysis. (PubMed, Schizophr Res) - "Newer antipsychotics (risperidone, amisulpride and paliperidone) and older antipsychotics (chlorpromazine, haloperidol and sulpride) increase prolactin levels with large effect sizes...In contrast to a previous review clozapine and zotepine were no longer associated with decreased prolactin levels compared to placebo. Risperidone's ranking has more implications supported by CINeMA. This NMA draws the conclusion with larger sample size and extends evidence to more literature in this field."

Journal • Retrospective data • Review • CNS Disorders • Psychiatry • Schizophrenia

Inhibitory Effects of Antipsychotics on the Contractile Response to Acetylcholine in Rat Urinary Bladder Smooth Muscles. (PubMed, Biol Pharm Bull) - "Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Psychiatry • Schizophrenia