Neuropsychopharmacology Reports最新文献

{"title":"Differential Neuronal Development in iPSC-Derived Neural Stem Cells From Monozygotic Twin Cases With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine.","authors":"Shotaro Kawano, Sayaka Katayama, Masaya Ogawa, Rei Endo, Naoto Ikeda, Yuuri Ikeuchi, Tomoki Mita, Hikari Takei, Nanaka Gotoda-Nishimura, Daiki Miura, Hotaka Fukushima, Hitoshi Hashimoto, Ryota Hashimoto, Takanobu Nakazawa","doi":"10.1002/npr2.70097","DOIUrl":"10.1002/npr2.70097","url":null,"abstract":"<p><p>Treatment-resistant schizophrenia (TRS) affects 20%-30% of individuals diagnosed with schizophrenia and is effectively managed with clozapine. However, the molecular and cellular mechanisms that underlie its efficacy remain largely unclear. We previously generated induced pluripotent stem cell (iPSC) lines from a unique pair of monozygotic twins with TRS. One twin responded to clozapine (CLZ-res), while the other did not (CLZ-non-res). Building on our previous study of these twins, we included healthy controls and focused on the early developmental stages of neuronal differentiation. To investigate the phenotypic differences in the developmental stages of neural cells between patient-derived cells, we differentiated each iPSC line-from both patients and healthy individuals-into neural stem cells (NSCs) and subsequently induced the differentiation of NSCs into neurons. Our results demonstrated that NSCs derived from patients' iPSC lines exhibited impaired neuronal differentiation, with a more pronounced reduction in differentiation observed in CLZ-non-res cells than in CLZ-res cells. RNA sequencing analysis revealed significant differences in the expression of genes involved in neuronal development between CLZ-res and CLZ-non-res cells. These findings suggest that the differences in neuronal development may contribute to the variability in clozapine responsiveness. Although this study is limited to a single twin pair, this unique human model provides valuable insights into the molecular and cellular mechanisms underlying differential clozapine responses, offering a promising framework for the development of effective treatments for patients with TRS.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70097"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Akathisia Induced by Metoclopramide in a Pregnant Woman With Nausea and Vomiting: A Case Report.","authors":"Ryohei Nakamura, Keisuke Noto, Toshinori Shirata, Yusuke Saito, Isao Takehara, Satoru Nagase, Akihito Suzuki","doi":"10.1002/npr2.70122","DOIUrl":"10.1002/npr2.70122","url":null,"abstract":"<p><strong>Background: </strong>Nausea and vomiting are common during pregnancy and can significantly impair maternal well-being. Metoclopramide is widely used to treat these symptoms but may cause extrapyramidal side effects, including akathisia. Akathisia is characterized by inner-restlessness and psychomotor agitation, which can be difficult to distinguish from perinatal anxiety disorders due to symptom overlap. Reports of metoclopramide-induced akathisia during pregnancy are limited.</p><p><strong>Case presentation: </strong>We report a case of metoclopramide-induced akathisia in a pregnant woman at 33 weeks of gestation with nausea and vomiting. She had been taking dextromethorphan for a COVID-19-related cough prior to admission. She was hospitalized for threatened preterm labor with abdominal tightness, and intravenous bolus infusions of metoclopramide were initiated for nausea, vomiting, and appetite loss. Shortly thereafter, she developed limb tremors and insomnia, followed by severe inner restlessness and psychomotor agitation. Suspecting anxiety disorders or akathisia, metoclopramide was discontinued and diazepam was started. Her symptoms improved within 3 days, with no recurrence after discontinuation of diazepam. Based on the clinical course and temporal relationship with metoclopramide administration, metoclopramide-induced akathisia was considered the most likely diagnosis.</p><p><strong>Conclusions: </strong>This case suggests that metoclopramide-induced akathisia can occur during pregnancy and may be misdiagnosed as a perinatal anxiety disorder. Rapid intravenous bolus administration is a known risk factor for metoclopramide-induced akathisia and may have increased the risk in this patient. In addition, a possible pharmacological interaction between metoclopramide and dextromethorphan, including a potential CYP2D6-related pharmacokinetic effect and central dopaminergic pharmacodynamic effect, may have contributed to akathisia. Greater awareness of this adverse effect may facilitate early recognition and appropriate management.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70122"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Incongruity of Lacosamide in the Management of Delirium Complicated by Ileus.","authors":"Takahiko Nagamine","doi":"10.1002/npr2.70131","DOIUrl":"10.1002/npr2.70131","url":null,"abstract":"<p><p>Delirium involves neurotransmitter imbalances and disrupted neural networks. Although lacosamide may theoretically treat delirium by reducing neuronal hyperexcitability via sodium channel modulation, clinical evidence is lacking. Sodium channels in the enteric nervous system mean lacosamide can cause gastrointestinal dysmotility independent of anticholinergic pathways. Given these risks and potential disruptions to the gut-brain axis, off-label use requires extreme caution and rigorous monitoring.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70131"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary Oxytocin and Socio-Emotional Functioning in Children and Adolescents With and Without Autism Spectrum Disorder.","authors":"Minobu Ikehara, Rio Ishida, Kazuhiko Yamamuro, Natsuko Kashida, Tsutomu Takeda, Michihiro Toritsuka, Manabu Makinodan","doi":"10.1002/npr2.70138","DOIUrl":"10.1002/npr2.70138","url":null,"abstract":"<p><strong>Aim: </strong>Given that alterations in oxytocinergic and immune systems have been implicated in the social and emotional difficulties of autism spectrum disorder (ASD), yet the associations between these biological factors and internal psychological constructs remain unclear, we examined the relationship between salivary oxytocin (OT) levels, inflammatory markers (interleukin-1β [IL-1β], IL-6, IL-8), self-esteem, and perceived social support in children and adolescents with and without ASD.</p><p><strong>Methods: </strong>26 children and adolescents with ASD and 23 typically developing (TD) controls were included. Salivary OT and inflammatory cytokine levels were measured using enzyme-linked immunosorbent and multiplex immunoassays.</p><p><strong>Results: </strong>Salivary oxytocin levels were significantly lower in the ASD group than in the TD group after adjusting for age. In contrast, no significant group differences were observed in inflammatory markers (IL-1β, IL-6, or IL-8). However, across participants, including those with ASD, higher OT levels were associated with greater self-esteem and perceived social support. These findings suggest that oxytocin-related socio-emotional processes may be associated with socio-emotional functioning across children and adolescents, including those with ASD. Participants with higher OT levels were associated with greater self-esteem and perceived social support. Among the inflammatory markers, none of the cytokines (IL-1β, IL-6, or IL-8) showed significant associations with the psychological measures, including AQ-J total scores.</p><p><strong>Conclusion: </strong>OT levels may be associated with socio-emotional functioning and psychological well-being across children and adolescents with and without ASD, regardless of diagnostic status. In contrast, no significant associations were observed between inflammatory markers and psychological measures in the present sample.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70138"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vortioxetine-Lurasidone Augmentation for Compulsive Scratching Behavior in Prader-Willi Syndrome: A Case Report.","authors":"Yasuhide Nagoshi","doi":"10.1002/npr2.70145","DOIUrl":"10.1002/npr2.70145","url":null,"abstract":"<p><strong>Background: </strong>Prader-Willi syndrome (PWS) is a rare genetic disorder frequently associated with repetitive and self-injurious behaviors such as skin picking. Effective pharmacological treatments for compulsive scratching behavior in PWS remain limited.</p><p><strong>Case presentation: </strong>We report the case of a 19-year-old woman with PWS presenting with severe, persistent scratching behavior resulting in repeated excoriations. Escitalopram produced partial improvement but was discontinued because of sedation. Treatment was switched to vortioxetine, which reduced the frequency of scratching but did not achieve remission. Subsequent augmentation with lurasidone resulted in marked improvement, with episodes decreasing from daily occurrences to once every 1-3 months and lasting only a few minutes. The patient remained stable for 2 years without recurrence of severe symptoms.</p><p><strong>Conclusion: </strong>This case suggests that vortioxetine and lurasidone may represent a potential pharmacological option for severe scratching behavior in PWS. Further studies are needed to clarify the therapeutic role of this combination approach.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70145"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen Gas Therapy in Schizophrenia: Potential Neuroprotective Effects From an Animal Study.","authors":"Nobumi Miyake, Toshiaki Haga, Shin-Ichi Hirano, Yusuke Ichikawa, Yoshiyo Oguchi, Kumiko Ando","doi":"10.1002/npr2.70117","DOIUrl":"10.1002/npr2.70117","url":null,"abstract":"<p><strong>Aims: </strong>Oxidative stress has recently emerged as a key factor in the pathophysiology of schizophrenia. This study investigated whether inhalation therapy with hydrogen gas, a selective antioxidant, could reduce oxidative stress and improve behavioral outcomes in an MK-801-induced schizophrenia-like mouse model.</p><p><strong>Methods: </strong>Six-week-old male C57BL/6 mice received chronic intraperitoneal injections of MK-801 (0.5 mg/kg) or saline for 4 weeks. A third group received MK-801 followed by hydrogen gas inhalation therapy. Behavioral assessments included the open-field test (OFT) to evaluate hyperactivity as an indicator of positive symptoms and the prepulse inhibition (PPI) test to assess cognitive dysfunction. Oxidative stress was evaluated by measuring whole-brain hydroxyl radical antioxidant capacity (HORAC) and total antioxidant capacity (TAC).</p><p><strong>Results: </strong>MK-801-treated mice exhibited significant hyperactivity in the OFT and a trend toward impaired PPI, confirming the schizophrenia-like phenotype. Hydrogen gas treatment did not produce significant improvements. MK-801 administration significantly reduced HORAC levels, whereas hydrogen gas therapy markedly restored them. No significant differences in TAC were observed among the groups.</p><p><strong>Conclusion: </strong>These findings suggest that hydrogen gas therapy does not significantly ameliorate behavioral abnormalities in the MK-801-induced schizophrenia-like mouse model but exerts beneficial antioxidant effects. Future studies should evaluate hydrogen gas as an adjunctive therapy and further assess its efficacy and safety in clinical settings.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70117"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13054952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione-Related Metabolite Levels and Enzyme Activities in Depression: A Systematic Review and Meta-Analysis.","authors":"Takahide Etani, Nobuaki Hondo, Sho Moriguchi, Kazunari Yoshida, Sotaro Moriyama, Koki Takahashi, Tahichi Moritake, Yumina Nakamura, Ryoma Kani, Shiori Honda, Masataka Wada, Sakiko Tsugawa, Yukino Mori, Hikari Segawa, Tony Kaku, Hiroyuki Uchida, Shinichiro Nakajima","doi":"10.1002/npr2.70125","DOIUrl":"10.1002/npr2.70125","url":null,"abstract":"<p><p>Recently, an increasing number of studies have reported abnormal levels of glutathione (GSH)-related metabolites and enzyme activities in neuroimaging and peripheral samples in patients with depression, indicating abnormalities in the GSH cycle in patients with depression. However, the abnormalities in the GSH cycle have not been comprehensively investigated. Here, we conducted a systematic review and meta-analysis to compare the levels of GSH-related metabolites (GSH and GSH disulfide [GSSG]) and the activities of GSH-related enzymes (Glutathione-peroxidase [GPx], GSH reductase [GR], glutamate-cysteine ligase [GCL], GSH synthetase [GS], and GSH S-transferase [GST]) between patients with depression and healthy controls (HC). The search was performed with MEDLINE, Embase, and PsychINFO. The inclusion criteria were studies comparing levels of GSH-related metabolites and enzyme activities between patients with depression and HC. Standardized mean differences were calculated to assess group differences. Thirty studies met the eligibility criteria, which included 1019 patients and 947 HC. Our meta-analysis indicated significantly decreased activity of GPx in patients with depression compared with HC, while the levels of GSH and GR were not significantly different between the groups. Because no studies, or an insufficient number of studies, have been conducted on GSSG, GST, GCL, and GS, meta-analyses were not performed for these metabolites and enzyme activities. Our findings suggest that abnormal cycling of the GSH system, particularly decreased GPx activity, is involved in the pathophysiology of depression and may serve as a potential biomarker for this illness. Furthermore, given that no or insufficient studies have been conducted on GSSG, GST, GCL, and GS, this study highlights the need for further research to fully elucidate the GSH cycle in patients with depression.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70125"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Management, Safety, and Outcomes in Bipolar Disorder: An Integrated Narrative Review of Clinical and Translational Evidence.","authors":"Gudisa Bereda","doi":"10.1002/npr2.70141","DOIUrl":"10.1002/npr2.70141","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) is a chronic psychiatric condition that requires careful pharmacological management. Ensuring treatment effectiveness, safety, adherence, and proper monitoring is essential, especially in pediatric, pregnant, and cognitively impaired patients.</p><p><strong>Objective: </strong>To review the available evidence on treatment outcomes, safety, adherence, and monitoring in bipolar disorder.</p><p><strong>Methods: </strong>A literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar. A comprehensive review of systematic reviews, meta-analyses, cohort studies, clinical trials, and case reports was performed. This review was guided by the Scale for the Assessment of Narrative Review Articles (SANRA) criteria. The findings were synthesized qualitatively.</p><p><strong>Results: </strong>This review highlights important challenges and therapeutic considerations in bipolar disorder management. Medication adherence and laboratory monitoring compliance were generally poor. Sleep disturbances were associated with poorer functional outcomes. Combination therapy reduced the risk of manic and depressive recurrence but may lower overall functioning in some patients. Lithium showed favorable long-term outcomes, including reduced sickness absence and lower mortality, whereas pregabalin was linked to poorer occupational outcomes. Untreated bipolar disorder during pregnancy was associated with prematurity and low birth weight. Mechanistically, lithium, valproate, and emerging agents may modulate neuroplasticity and intracellular signaling pathways; however, evidence for cognitive improvement remains limited and inconsistent.</p><p><strong>Conclusion: </strong>Lithium and combination therapies improve relapse prevention, cognitive outcomes, and mortality. However, adverse effects and poor adherence remain challenges. Individualized strategies, regular monitoring, and tailored interventions are essential to optimize care.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70141"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in White Blood Cell and Neutrophil Counts in Patients With Schizophrenia Treated With Lithium Carbonate, Adenine, and Ninjin-Yoei-To: A Preliminary Study.","authors":"Teruyuki Matsuoka, Sumihiro Yamano","doi":"10.1002/npr2.70144","DOIUrl":"10.1002/npr2.70144","url":null,"abstract":"<p><strong>Aim: </strong>Clozapine is often unavailable to patients with treatment-resistant schizophrenia when white blood cell (WBC) and neutrophil counts do not meet the required thresholds. This study aimed to examine changes in WBC and neutrophil counts and the factors associated with these changes.</p><p><strong>Methods: </strong>Thirty-five patients with schizophrenia who received adenine, Ninjin-yoei-to, or lithium carbonate were included in the treatment group. Eighty-one patients with schizophrenia comprised the control group. A two-way mixed analysis of variance (ANOVA) was used to compare changes in WBC and neutrophil counts before and after treatment. Stepwise multiple regression analyses were conducted to identify factors associated with changes in WBC and neutrophil counts.</p><p><strong>Results: </strong>In the two-way mixed ANOVA, WBC and neutrophil counts in the treatment group were significantly lower than those in the control group at baseline (p < 0.001), and the counts at the final examination were significantly higher than the baseline values in the treatment group (p < 0.001). Stepwise multiple regression analyses revealed that adenine and lithium carbonate were significant predictors of changes in WBC (adjusted R² = 0.173, p < 0.001) and neutrophil counts (adjusted R² = 0.175, p < 0.001).</p><p><strong>Conclusion: </strong>Lithium carbonate and adenine may help increase the WBC and neutrophil counts in patients with schizophrenia. These agents may be useful for patients with low WBC and neutrophil counts prior to initiating clozapine treatment.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70144"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Repeated Smoking and Quitting Cigarettes on Plasma Concentrations of Clozapine and Its N-Desmethyl and N-Oxide Metabolites in a Japanese Patient With Schizophrenia.","authors":"Kazuro Ikawa, Norifumi Morikawa, Mutsumi Sakata, Naoki Horikawa","doi":"10.1002/npr2.70121","DOIUrl":"10.1002/npr2.70121","url":null,"abstract":"<p><p>Clozapine (CLZ) is used for treatment-resistant schizophrenia. However, its pharmacokinetics in Japanese patients with schizophrenia have not been well described. Smoking affects the activities of cytochrome P450 (CYP), which mainly metabolizes CLZ, and patients with schizophrenia have a higher rate of smoking than others. Hence, the effects of smoking or quitting cigarettes on CLZ pharmacokinetics have been reported. Nevertheless, there are no case reports on interactions with CLZ, particularly examining OCLZ concentrations over time during repeated periods of smoking and quitting cigarettes. In a Japanese man in his 40s, trough plasma concentrations of CLZ, N-desmethyl clozapine (NCLZ) and N-oxide clozapine (OCLZ) were measured, and their ratios and the daily dose (D) were evaluated as indicators of drug metabolism. The CLZ/D ratio ([ng/mL]/[mg/day]) decreased by a median of 58.2%, whereas both NCLZ/CLZ and OCLZ/CLZ ratios increased by medians of 64.7% and 58.6%, respectively, in the total smoking period, relative to the total quitting period. The drug concentrations and their metabolic ratios fluctuated with smoking (six cigarettes daily) on and off multiple times. These results suggest that the CYP1A2-inducing effect of smoking on CLZ metabolism can be reproducible and emphasize the need for careful attention to smoking status changes, CLZ concentration measurement and dose checking in patients with schizophrenia who have a smoking habit. Further studies are required to confirm the pharmacokinetic findings obtained from the limited data in only one patient.</p>","PeriodicalId":19137,"journal":{"name":"Neuropsychopharmacology Reports","volume":"46 2","pages":"e70121"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}