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AIM: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. METHODS: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score. RESULTS: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score. CONCLUSION: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.
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INTRODUCTION: Whether psychiatric symptoms after recovery from coronavirus disease 2019 (COVID-19) are specific to this illness remains unclear. METHODS: In this retrospective study, the Diagnosis Procedure Combination data and outpatient clinic data were used for patients who received inpatient treatment in Saiseikai-affiliated hospitals for COVID-19 or other respiratory tract infections (non-COVID) from 2020 to 2022. The primary outcome was new prescriptions of psychotropic drugs after discharge (i. e., prescriptions of psychotropics to patients who had not received them before or during their hospitalization). Values of interest were compared between groups using the chi-square test or Fisher's exact test. A COX proportional-hazards model was used to examine factors associated with psychotropic prescriptions after discharge in age- and sex-matched COVID-19 and non-COVID patients. RESULTS: Of 31,993 chart records, 19,613 were excluded due to a positive history with psychiatric disorders (n=2,445), prescriptions of psychotropics (n=744), and no follow-ups (n=16,424). Thus, 3,648 COVID-19 and 8,732 non-COVID patients were included (mean [range] duration of follow-up, days: 146.9 [1-727] and 239.2 [1-729], respectively). Two hundred and four (5.6%) of the 3,648 patients with COVID-19 received psychotropic prescriptions after discharge. No statistically significant differences were observed in the prescription rates of any psychotropic category between the COVID-19 and non-COVID groups. An increase in severity during hospitalization was significantly associated with more frequent psychotropic prescriptions (hazard ratio 1.83, p<0.001). DISCUSSION: The development of psychiatric symptoms should be closely observed, especially in patients who experienced increased severity during hospitalization, regardless of whether they suffered from COVID-19.
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COVID-19 , Alta do Paciente , Psicotrópicos , Humanos , Masculino , Feminino , Psicotrópicos/uso terapêutico , COVID-19/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos , Alta do Paciente/estatística & dados numéricos , Adulto , Idoso , Infecções Respiratórias/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Transtornos Mentais/tratamento farmacológico , Adulto Jovem , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricosRESUMO
INTRODUCTION: Predictors of treatment response to intravenous ketamine remain unclear in patients with treatment-resistant depression (TRD); therefore, this study aimed to clarify these predictors using the US National Institutes of Health database of clinical trials. METHODS: Data from a placebo-controlled, double-blind, randomized controlled trial were used to assess the efficacy of intravenous ketamine in adult patients with TRD (NCT01920555). For the analysis, data were used from the participants who had received therapeutic doses of intravenous ketamine (i. e., 0.5 and 1.0 mg/kg). Logistic and multivariable regression analyses were conducted to explore the demographic and clinical factors associated with response to treatment or changes in the Hamilton Depression Rating Scale 6 items (HAM-D-6) total score. RESULTS: This study included 31 patients with TRD (13 women; mean±standard deviation age, 48.4±10.9 years). Logistic regression analysis showed that the age of onset was positively correlated with treatment response after three days of ketamine administration (ß=0.08, p=0.037); however, no association was observed between treatment response and age, sex, baseline HAM-D-6 total score, or dissociative score assessed with the Clinician-Administered Dissociative States Scale 40 min after ketamine infusion. Multiple regression analysis showed that no factors were correlated significantly with the percentage change in the HAM-D-6 total score three days after ketamine administration. DISCUSSION: Later disease onset correlates with a better treatment response three days after ketamine infusion in patients with TRD. Glutamatergic signal transmission may be impaired in patients with an earlier onset of depression, resulting in decreased neuroplasticity, which diminishes ketamine response.
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Transtorno Depressivo Resistente a Tratamento , Ketamina , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Recém-Nascido , Ketamina/uso terapêutico , Depressão/tratamento farmacológico , Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Método Duplo-Cego , Resultado do Tratamento , Infusões IntravenosasRESUMO
Objective: Although anesthetics play an important role in electroconvulsive therapy (ECT), the clinical efficacy and seizure adequacy of sevoflurane in the course of ECT remain unclear. The purpose of this study was to examine the clinical efficacy and seizure adequacy of sevoflurane, compared with those of thiopental, in the course of ECT in patients with mood disorders. Methods: We conducted a retrospective chart review. Patients who underwent a course of ECT and received sevoflurane (n = 26) or thiopental (n = 26) were included. Factors associated with ECT and treatment outcomes were compared between the two groups using propensity score (PS) matching. Between-group differences were examined using an independent t-test for continuous variables and a χ2-test for categorical variables. Results: Patients who received sevoflurane needed more stimulations (sevoflurane: 13.2 ± 4 times, thiopental: 10.0 ± 2.5 times, df = 51, p = 0.001) and sessions (sevoflurane: 10.0 ± 2.1 times, thiopental: 8.4 ± 2.1 times, df = 51, p = 0.01) and had more inadequate seizures (sevoflurane: 5 ± 3.9 times, thiopental: 2.7 ± 2.7 times, df = 51, p = 0.015). Remission and response rates were similar in both groups. Conclusion: The present findings indicate that sevoflurane should be used with caution in ECT and only when the clinical rationale is clear.
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INTRODUCTION: This study investigated combined prescriptions of drugs for mood disorders and physical comorbidities that need special attention in the light of frequent physical comorbidities in patients with mood disorders. METHODS: We used the claims sampling data of 581,990 outpatients in January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Fisher's exact test was performed to compare the prescription rates of non-steroidal anti-inflammatory drugs (NSAIDs), loop/thiazide diuretics, angiotensin-converting enzyme inhibitors, and/or angiotensin II receptor blockers between lithium users and age- and sex-matched non-lithium users; NSAIDs, antiplatelet drugs, and/or anticoagulants between selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline reuptake inhibitor (SNRI) users and non-users; warfarin between mirtazapine users and non-users; and the proportions of patients in the two groups with a diagnosis of somatic conditions for which these medications were indicated and actually received them. A Bonferroni corrected p-value of<0.05/3 was considered statistically significant. RESULTS: Prescriptions of the above-mentioned medications were less frequent in lithium and mirtazapine users and comparable in SSRI/SNRI users, compared to non-users (18.3 vs. 31.9%, p=7.6×10-10; 0.78 vs. 1.65%, p=0.01; 23.1 vs. 24.1%, p=0.044). In a subgroup of patients with somatic diseases for which these medications were indicated, the prescription rates were comparable in lithium and mirtazapine users and higher in SSRI/SNRI users compared to non-users (28.0 vs. 29.4%, p=0.73; 4.7 vs. 7.4%, p=0.28; 35.6 vs. 33.4%, p=0.0026). DISCUSSION: Pharmacotherapy with drugs for mood disorders and physical comorbidities that require attention was commonly observed in clinical practice.