Pharmacopsychiatry最新文献

{"title":"Mood destabilizers?: A review of mood stabilizer-associated mania.","authors":"Shaina E Schwartz, Allyson M Hundley, Chak Yui M Chan, Angela R Baalmann","doi":"10.1055/a-2934-0429","DOIUrl":"https://doi.org/10.1055/a-2934-0429","url":null,"abstract":"<p><strong>Abstract: </strong>Mania is associated with significant morbidity and mortality. Mood stabilizing medications are typically used to prevent manic episodes, yet in some cases can precipitate them. The literature on this rare but potentially serious paradoxical reaction is lacking. A structured literature review was performed to identify case reports of adults experiencing manic symptoms associated with the routine use of medications with mood stabilizing properties (i.e., valproate, lithium, carbamazepine, lamotrigine, oxcarbazepine, and topiramate). A total of eight articles describing 12 unique patients were included in the analysis. The majority of patients (58%) had a previous diagnosis of bipolar spectrum disorder. The most frequent offending agent was lamotrigine (58%), followed by topiramate (33%), and carbamazepine (8%). Most patients (92%) were taking concomitant medications, mainly antipsychotics (50%) and other mood stabilizers (50%). The mean time between treatment initiation or dose escalation of the mood stabilizer and the onset of mania was 7 days. In all but two cases, the mood stabilizer was discontinued upon presentation. Improvement in symptoms was observed within a mean of 9 days following intervention. Mood stabilizer-associated mania appears to be relatively acute in onset and can be reversed by discontinuation. It commonly, but not exclusively, occurs in patients with a history of bipolar spectrum disorder who are already prescribed medications with mood stabilizing properties. In cases of new onset or worsening mania following the initiation or dose escalation of a mood stabilizer (especially lamotrigine and topiramate), this paradoxical reaction should be considered.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Etifoxine and Alprazolam on Pregnenolone, Cortisol, and 18-kDa Translocator Protein in Healthy Men: A Placebo-Controlled Study.","authors":"Marco Riebel, Lisa-Marie Brunner, Doris Melchner, Anett Dörfelt, Jens Volkmar Schwarzbach, Rainer Rupprecht, Caroline Nothdurfter","doi":"10.1055/a-2935-8784","DOIUrl":"https://doi.org/10.1055/a-2935-8784","url":null,"abstract":"<p><strong>Abstract: </strong>INTRODUCTION:: The non-benzodiazepine anxiolytic etifoxine is hypothesized to act as a neurosteroidogenic agent via the 18-kDa translocator protein. In a placebo controlled design, we compared its steroidogenic effects with those of alprazolam.</p><p><strong>Abstract: </strong>METHODS:: In a double-blind within-subject design, healthy male participants (<i>N</i>=29) received etifoxine (150 mg/d), alprazolam (1.5 mg/d), and placebo in randomised order for 5 days. Pregnenolone expression and cortisol expression were assessed at the end of each treatment in the morning, and at four time points in the afternoon. Thrombocyte 18-kDa translocator protein expression was measured in the morning.</p><p><strong>Abstract: </strong>RESULTS:: Analysis of morning samples revealed higher 18-kDa translocator protein expression (<i>χ</i> ²=7.41 and <i>p</i>=0.025) after etifoxine intake compared to alprazolam intake (<i>p</i>=0.025). Both alprazolam and etifoxine were associated with lower pregnenolone levels (<i>p</i><0.005). The 18-kDa translocator protein did not mediate the medication effects on pregnenolone (average causal mediation effects for etifoxine vs. placebo contrast: <i>p</i>=0.276). Afternoon measurements showed that alprazolam reduced cortisol (<i>χ</i> ²=66.76, <i>p</i><0.001), and that both alprazolam and etifoxine reduced pregnenolone levels (<i>χ</i> ²=31.75, <i>p</i><0.001). State anxiety was only marginally lowered by medication (<i>p</i>=0.092), and no biological markers-cortisol, pregnenolone, or 18-kDa translocator protein-predicted anxiety ratings (all <i>p</i> > 0.40).</p><p><strong>Abstract: </strong>CONCLUSIONS:: We confirmed the effects of benzodiazepines on cortisol and pregnenolone levels in healthy male participants. Etifoxine administration was associated with a decrease in peripheral plasma pregnenolone. Taken together, however, plasma pregnenolone levels do not seem to reflect etifoxine binding to 18-kDa translocator protein and central anxiolytic mechanisms in humans.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pipamperone metabolism by various recombinant cytochrome preparations.","authors":"Tamara Pfaff, Burkhard Hinz, Udo I Walther","doi":"10.1055/a-2894-5577","DOIUrl":"10.1055/a-2894-5577","url":null,"abstract":"<p><strong>Introduction: </strong>The evaluation of pharmacokinetic interactions is based on the knowledge of enzymatic metabolization by cytochrome 450 enzymes or cellular transport processes. Research on the metabolism of pipamperone, an antipsychotic of the butyrophenone family, has not yet yielded conclusive results. In the present in vitro study, human cytochrome enzymes were investigated for their possible involvement in the metabolism of pipamperone.</p><p><strong>Methods: </strong>The recombinant human cytochrome enzymes tested, i.e. CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, were commercially available. The U.S. Food and Drug Administration-recommended clinical index substrates were used to establish appropriate incubation conditions for each enzyme. All substrates and their metabolites were analyzed by gas chromatography-mass spectrometry. After incubation, the amount of metabolites formed and the concentration of remaining pipamperone were measured. In addition, the metabolites from these in vitro experiments were compared with the metabolites found in the urine of pipamperone-treated patients and with those produced in a cell culture experiment.</p><p><strong>Results: </strong>Overall, various cytochrome enzymes showed a low turnover of pipamperone. Only CYP2D6 and CYP3A4 caused statistically significant changes in both a decrease in pipamperone concentrations and an increase in metabolites. CYP3A4 proved to be the isoform that metabolized pipamperone most strongly, producing the same metabolite as all other CYP isoenzymes. It is noteworthy that this and other metabolites were also detected in the patients' urine samples.</p><p><strong>Conclusions: </strong>Our results suggest that, alongside the tested cytochrome enzymes, other phase I metabolizing systems likely play a role in pipamperone metabolism.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium Prescription in Unipolar Depression: Findings from a Nationwide Greek Cohort Study.","authors":"Vasilios Karageorgiou, Ioannis Michopoulos, Michail Hadjulis, Panagiota Mitrou, Eleftherios Thireos, Konstantinos Mathioudakis, Petros Skapinakis, Rossetos Gournellis","doi":"10.1055/a-2924-4384","DOIUrl":"https://doi.org/10.1055/a-2924-4384","url":null,"abstract":"<p><strong>Abstract: </strong>INTRODUCTION: Lithium is a well-evidenced option for treatment-resistant unipolar depression. However, its use has globally declined over the past two decades and there is little evidence on exactly how unpopular the unipolar augmentation strategy is on the nosological characteristics of patients who still receive it and on primary agents. Real-world epidemiological studies can provide key relevant insights.</p><p><strong>Abstract: </strong>METHODS: We analysed all ICD-10 unipolar depression prescriptions in Greece in the period between 1/2/2019 and 31/1/2020 and identified unipolar depression patients who were prescribed lithium. To benchmark lithium rates against those of other alternatives, we estimated quetiapine and aripiprazole prescription rates in unipolar depression. Logistic regression models were used to locate the diagnostic predictors of lithium prescription. Polypharmacy patterns and co-prescription of potentially interacting drugs were examined.</p><p><strong>Abstract: </strong>RESULTS: Only 1,314 patients (0.174%) with unipolar depression were prescribed lithium, representing a small fraction of the assumed 30% of patients expected to have treatment-resistant depression. This was substantially lower than quetiapine (7.1%) and aripiprazole (1.1%) prescription rates for unipolar depression. Patients who were prescribed lithium were younger, more often men, and mostly managed by psychiatrists. More severe disorder profiles were apparent (24% vs. 6%), with psychotic symptoms and mixed symptomatology more prevalent. The sensitivity analysis showed that, after excluding patients prescribed lithium who received a diagnosis suggestive of bipolarity within the same period, only 785 patients (0.108%) consistently received unipolar diagnoses, with a further drop when other major diagnoses are factored in (0.08%). One in 13 people received a possibly interacting drug, especially thiazide diuretics.</p><p><strong>Abstract: </strong>DISCUSSION: Despite strong evidence for augmentation in treatment-resistant unipolar depression, lithium prescription remains an underappreciated treatment option. In Greece, it is reserved for severe cases, together with selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors and atypical antipsychotics. Possible reasons include a perception of alternatives as safer, further complicated by supply issues.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guideline adherence in patients with long-term schizophrenia in Germany: Focus on clozapine and electroconvulsive therapy.","authors":"Berend Malchow, Paul-Fabian Mühl, Michael Belz, Anke Bramesfeld, Elias Wagner, Jens Wiltfang, Alkomiet Hasan, David Zilles-Wegner","doi":"10.1055/a-2899-9948","DOIUrl":"https://doi.org/10.1055/a-2899-9948","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies suggest a problem in the care of long-term patients in psychiatry, i.e., patients with long hospitalizations and no indication for acute inpatient treatment. Long stays are often associated with treatment resistance, for which evidence-based guideline recommendations exist for patients with schizophrenia. The aim of this study is to assess and characterize long-term patients in German psychiatric clinics and analyze the implementation of guideline recommendations for treatment-resistant schizophrenia.</p><p><strong>Methods: </strong>An anonymous online questionnaire was distributed to the management of 218 acute psychiatric clinics in Germany. The survey covered structural characteristics of the clinic, the number and diagnoses of long-term patients, and the implementation of guideline recommendations for patients with treatment-resistant schizophrenia.</p><p><strong>Results: </strong>At the time of the survey, two-thirds of the responding clinics were treating long-term patients. Over 60% (<i>n</i>=45) of these patients had a diagnosis from the schizophrenia spectrum, with an average length of stay of 267 days. A total of 82.2% of patients with schizophrenia received antipsychotic therapy, 53% received clozapine, and 15.6% received electroconvulsive therapy. The most common reason for not receiving clozapine and electroconvulsive therapy was lack of consent.</p><p><strong>Discussion: </strong>The survey confirms the unresolved problem of long-term patients in acute psychiatric clinics. In addition to demands for improved care structures for people with severe and chronic mental illnesses, the quality of acute psychiatric treatment (guideline adherence) must also be questioned. From an ethical viewpoint, short-term nonvoluntary measures aimed at restoring capacity to consent need to be weighed up against long-term or even permanent detention.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and tolerability of nutraceuticals and phytotherapics for antipsychotic-induced weight gain in schizophrenia spectrum disorders: Systematic review and meta-analysis.","authors":"Antonio Di Francesco, Antonio Munafò, Gaetano Catania, Sofia Francesca Aprile, Salvatore Canonico, Carmen Concerto, Alessandro Rodolico, Maria Salvina Signorelli, Stefan Leucht, Filippo Caraci","doi":"10.1055/a-2869-0635","DOIUrl":"https://doi.org/10.1055/a-2869-0635","url":null,"abstract":"<p><strong>Abstract: </strong>Antipsychotic drugs frequently cause metabolic complications in people with schizophrenia spectrum disorders, increasing cardiovascular morbidity and contributing to premature mortality; nutraceutical and phytotherapeutic agents may offer accessible adjunctive strategies, but their efficacy in this setting remains uncertain. We conducted a systematic review and meta-analysis (PROSPERO: CRD42024616494) of randomized controlled trials comparing nutraceuticals/phytotherapics with placebo in adults (18-65 years) with schizophrenia spectrum disorders receiving antipsychotics, including interventions lasting at least 4 weeks. Primary outcomes were body weight change and all-cause treatment discontinuation; secondary outcomes included lipid profile, glucose homeostasis, blood pressure, and anthropometric measures. Two independent reviewers extracted data and assessed study quality using the Cochrane Risk of Bias 2 tool, and meta-analyses primarily used random-effects models. Twenty-one trials (1,426 participants) evaluating 16 interventions were included. Omega-3 fatty acids, probiotics combined with dietary fibers, and Liuyu decoction were each associated with reduced body weight versus placebo, while alpha-lipoic acid showed consistent triglyceride reductions across two independent trials and berberine reduced systolic blood pressure. Discontinuation rates did not differ between groups, but risk of bias was frequently substantial, mainly due to blinding limitations and missing data handling. Overall, alpha-lipoic acid for hypertriglyceridemia and berberine for hypertension have the most consistent multi-trial support, whereas single-trial findings for omega-3s, probiotic combinations, and traditional Chinese medicine preparations require replication; heterogeneity and methodological weaknesses currently preclude broad clinical recommendations, though selected nutraceuticals may be considered for specific metabolic targets.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of seizure quality markers with postictal autonomic tone-the postictal heart rate correlates with seizure duration in electroconvulsive therapy.","authors":"Imrich Blasko, Magdalena Bühler, Lukas Gasteiger, Daniel Niederbrunner, Timo Schurr, Laurin Mauracher","doi":"10.1055/a-2890-8455","DOIUrl":"https://doi.org/10.1055/a-2890-8455","url":null,"abstract":"<p><strong>Background and objectives: </strong>Hemodynamic changes constitute a component of the autonomic nervous system arousal in response to seizures induced by electroconvulsive therapy. Fluctuations in heart rate and blood pressure are the result of changes in the tone of the autonomic nervous system. This study investigates how changes in heart rate and blood pressure rate are related to electroconvulsive therapy quality parameters.</p><p><strong>Methods: </strong>The heart rate and blood pressure values from 29 patients across 112 sessions were retrospectively assessed and associated with electroconvulsive therapy seizure parameters. Electroconvulsive therapy seizure parameters, i.e., the stimulation charge, duration of the electroencephalography seizure, postictal suppression index, average seizure energy index, maximum sustained coherence, and mid-ictal amplitude, were used in linear mixed-effects models.</p><p><strong>Results: </strong>The duration of the seizure predicted the postictal increase in heart rate, independently on the applied stimulus charge, parameters of seizure properties or interhemispheric synchronicity and postictal central inhibition capacity. Systolic and diastolic blood pressures showed only a non‑significant trend toward an increase after the electroconvulsive therapy seizure.</p><p><strong>Conclusions: </strong>Efforts to prolong the seizure duration while optimizing electroconvulsive therapy quality parameters may be associated with an elevated heart rate and may confer an additional burden for patients with cardiac disease.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ongoing Changes in Web Searches for Health-Related Information.","authors":"Eric D Achtyes, Tasha Glenn, John R Geddes, Rita Bauer, Michael Bauer, Michael Gitlin, Scott Monteith","doi":"10.1055/a-2896-4218","DOIUrl":"https://doi.org/10.1055/a-2896-4218","url":null,"abstract":"","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greater Depressive Symptom Severity is Associated with Increased Odds of Analgesic Use.","authors":"Shakila Meshkat, Qiaowei Lin, Aida Golshan, Vanessa K Tassone, Reinhard Janssen-Aguilar, Wendy Lou, Venkat Bhat","doi":"10.1055/a-2892-1148","DOIUrl":"10.1055/a-2892-1148","url":null,"abstract":"<p><strong>Introduction: </strong>Although pain and depression frequently co-occur, the relationship between depressive symptom severity and both the odds and duration of analgesic use remains underexplored. This study investigated the relationship between depressive symptoms and analgesic use, with particular attention to the duration of use.</p><p><strong>Methods: </strong>A cross-sectional analysis was conducted using data from the 2005-2018 National Health and Nutrition Examination Survey. Depressive symptoms were assessed using the Patient Health Questionnaire-9.</p><p><strong>Results: </strong>A total of 36,023 participants (51.14% women) were included. Each 1-point increase in the Patient Health Questionnaire-9 score was associated with a higher likelihood of analgesic use (adjusted odds ratio=1.08 and 95% confidence interval: 1.07-1.09). Compared to individuals with minimal depressive symptoms, those with mild (adjusted odds ratio=1.66 and 95% confidence interval: 1.45-1.90), moderate (adjusted odds ratio=2.17 and 95% confidence interval: 1.77-2.67), and severe symptoms (adjusted odds ratio=2.97, 95% confidence interval: 2.41-3.67) had progressively higher odds of analgesic use. Overall, depressive symptoms were associated with more than twice the odds of analgesic use (adjusted odds ratio=2.13 and 95% confidence interval: 1.82-2.48). Higher Patient Health Questionnaire-9 scores were associated with increased odds of longer analgesic use (>15 d; adjusted odds ratio=1.05 and 95% confidence interval: 1.02-1.08), as was the presence of depressive symptoms (adjusted odds ratio=1.73 and 95% confidence interval: 1.21-2.48). This association was most pronounced among individuals with severe depressive symptoms (adjusted odds ratio=2.58 and 95% confidence interval: 1.46-4.57).</p><p><strong>Discussion: </strong>Depressive symptoms were significantly associated with both increased likelihood and longer duration of analgesic use. These findings highlight the complex and potentially bidirectional relationship between pain and mental health, suggesting the need for integrated approaches to pain management and psychiatric care.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Intravenous Ketamine Treatment and Cognitive Function in Patients with Treatment-Resistant Depression: A Double-Blind, Randomized, Placebo-Controlled Trial.","authors":"Kie Nomoto, Yohei Ohtani, Taisuke Yatomi, Kengo Yonezawa, Sota Tomiyama, Nobuhiro Nagai, Keisuke Kusudo, Shiori Honda, Sotaro Moriyama, Shinichiro Nakajima, Mie Matsui, Takashige Yamada, Hiroshi Morisaki, Kimio Yoshimura, Tsuyoshi Eiro, Sakiko Tsugawa, Sadamitsu Ichijo, Yu Fujimoto, Tomoyuki Miyazaki, Takuya Takahashi, Hiroyuki Uchida, Hideaki Tani","doi":"10.1055/a-2894-5681","DOIUrl":"https://doi.org/10.1055/a-2894-5681","url":null,"abstract":"<p><strong>Introduction: </strong>While the rapid and robust effects of ketamine on depressive symptoms in treatment-resistant depression (TRD) have been demonstrated, the influence of ketamine treatment on cognitive function has not yet been fully elucidated. We aimed to evaluate the effects of ketamine treatment on cognitive function as part of a study that investigated the efficacy of repeated ketamine administration in patients with TRD. In addition, we conducted an exploratory analysis to examine whether baseline cognitive function was associated with ketamine response.</p><p><strong>Methods: </strong>In this double-blind, randomized, placebo-controlled study, 34 Japanese TRD patients were enrolled and assigned randomly into either ketamine or placebo group. They received ketamine 0.5 mg/kg or saline intravenously for four doses. Objective and subjective cognitive functions were evaluated with a comprehensive assessment battery before and after the intervention. We also assessed depressive symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS). The response was defined by at least a 50% reduction in the total MADRS score.</p><p><strong>Results: </strong>No significant differences were found between the ketamine and placebo groups on objective or subjective cognitive function scale score changes. Moreover, ketamine responders showed a significant improvement in subjective cognitive function compared to non-responders. The participants who demonstrated less inhibitory control at baseline showed greater MADRS score reductions after the ketamine treatment.</p><p><strong>Discussion: </strong>Repeated ketamine administration did not significantly deteriorate cognitive function compared to placebo, which supports a possible cognitive safety profile in patients with TRD. In addition, baseline impaired cognitive control may be associated with ketamine response.</p>","PeriodicalId":19783,"journal":{"name":"Pharmacopsychiatry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}