Treatment Of Treatment-resistant Depression Research Articles

Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression: A protocol for systematic review and meta-analysis.

Major Depressive Disorder (MDD) is a global health issue, and a significant portion of individuals with MDD experience Treatment-Resistant Depression (TRD), characterized by the lack of response to adequately trialed antidepressant medication and therapy. This systematic review aims to investigate the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) as an intervention for individuals with TRD. We will conduct a thorough search for publications of randomized clinical trials and quasi-experimental studies in MEDLINE, Embase, PsycINFO, Web of Science databases, and ClinicalTrials.gov. Furthermore, reference lists of included studies will be manually screened for additional relevant articles, with no restrictions on language or publication date. The search will be conducted from the inception of the databases until June 2024. Our PICO-guided research questions are: (1) In adults with Treatment-Resistant Depression, is MBCT more effective than standard care or other active treatments in reducing depressive symptoms? (2) In adults with Treatment-Resistant Depression, does MBCT demonstrate a comparable safety profile to standard care or other active treatments? The quality of the included studies will be assessed independently using the Cochrane Risk of Bias Tool (RoB 2). This study seeks to evaluate the effectiveness and tolerability of Mindfulness-Based Cognitive Therapy as an intervention for Treatment-Resistant Depression, and will employ the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to appraise the confidence in the evidence. Prospero registration ID: CRD42023411978. Registered on April 07, 2023.

Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study

BackgroundKetamine has recently gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer side effects, and is easier and cheaper to administer than both IV and IN routes. MethodsIn this context, we conducted an open-label clinical trial for investigating the efficacy and safety of 8 weekly sessions of SC esketamine in TRD patients (n = 30). ResultsAt the end of the treatment, a partial response rate of 26.09 %, a response rate of 52.17 % and remission rate of 34.78 % were observed. The self-reported depressive symptoms, as measured by the Beck Depression Inventory II, significantly decreased from the baseline to the final session, and the improvements were sustained throughout the week. Follow-up evaluations up to the sixth month consistently showed scores lower than the baseline. LimitationsThe small sample size and the drop-out during the follow-up phase may limit the generalizability of the findings. Additionally, the absence of a control group necessitates cautious interpretation of causality. ConclusionsThis pioneering study, which addresses SC esketamine treatment for TRD, reported promising response and remission rates, as well as sustained effects. It highlights the need for further research to improve and expand our knowledge of this innovative, more accessible, and cost-effective therapeutic approach.

Predictors of response to accelerated rTMS in the treatment of treatment-resistant depression.

Accelerated repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for treatment-resistant depression (TRD). We aimed to investigate the existence of clinical predictive factors in response to accelerated rTMS in the treatment of TRD. In total, 119 TRD patients who received accelerated rTMS were included in this study. The stimulation protocol was 15Hz stimulation over the the left dorsolateral prefrontal cortex. The protocol consisted of 25 sessions, each session lasting 30min for a total of 3000 pulses. Five sessions were applied per day for 5 consecutive days. At baseline (T0), day 5 (immediately after treatment) (T1), 4 weeks after treatment (T2), depression severity was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17), cognitive function was evaluated using Wisconsin Card Sorting Test (WCST), the intensity of suicidal ideation was evaluated using the Columbia-Suicide Severity Rating Scale (C-SSRS). Systemic immune-inflammation index (SII) was calculated at T0 and T2. The HAMD-17 scores, WCST performance, the C-SSRS scores at T1 and T2 were improved from T0 (P < 0.01). The SII at T2 was lower than at T0 (P < 0.01). The response rates at T1 and T2 were 57.98% (69/119) and 48.74% (58/119), respectively. The results of binary logistic analysis showed that shorter course of depression, two failed antidepressant trials, no history of ECT treatment, and lower levels of SII were predictive factors for accelerated rTMS treatment response at T1 and T2 (P < 0.05), while not having a history of hospitalization was a predictive factor for response at T2 (P < 0.05) but not at T1 (P > 0.05). Based on ROC curve analysis, the optimal cut-off values of SII for discriminating responders from non-responders at T1 and T2 were < 478.56 and < 485.03, respectively. The AUC of SII at T0 predicting response for T1 and T2 were 0.729 and 0.797. We found several clinical predictors of better responses to the accelerated rTMS. Identifying clinical predictors of response is relevant to personalize and adapt rTMS protocols in TRD patients.

Comparative Short- and Long-Term Effectiveness and Safety of Pramipexole and Aripiprazole Augmentation in Treatment-Resistant Unipolar Depression: An Observational Study.

This study compares the short- and long-term effectiveness and safety of pramipexole augmentation (PA) and aripiprazole augmentation (AA) for unipolar treatment-resistant depression (TRD). Patients were recruited in a private out-patients clinic specializing in mood disorders. At intake and at each visit, depressive and (hypo)manic symptoms, clinical status, and level of functioning were evaluated with appropriate scales. The trend of outcomes was analyzed using mixed-effect linear regression models. The study includes 81 patients with unipolar TRD treated with PA and 51 with AA. After 12 and 24 weeks of treatment with PA, the predicted response (64.1% and 76.2%) and remission rates (49.7% and 72.7%) were significantly higher than the predicted response (32.2% and 38.0%) and remission rates (18.9% and 28.1%) for AA. The improvement in psychosocial functioning was significantly greater and faster in PA than in AA. PA showed significant superiority over AA as a maintenance strategy (time spent ill and psychosocial functioning) up to 12 months. No difference in safety was found at each time point. PA could be an alternative option for the short- and long-term treatment of unipolar TRD, more effective than AA and similar in safety. These preliminary results need confirmation from randomized clinical trials.

Efficacy and Controversies Surrounding Electroconvulsive Therapy for Treatment-Resistant Depression: A Literature Review

Electroconvulsive therapy (ECT) remains a vital treatment option for individuals with treatment-resistant depression (TRD). Despite its historical stigma, controversy, and limited accessibility, ECT has been demonstrated to be beneficial and effective in severe cases of depressive disorders, where medication fails to produce results. It has been utilized since 1938 as a therapeutic technique for various psychiatric disorders, often used as an alternative to chemically induced seizures. The public’s perspectives on ECT hold significance as they can shape attitudes toward patients undergoing this therapy and the discrimination associated with receiving ECT. Additionally, the perspectives of patients who may benefit from ECT and those who are already undergoing treatment are crucial as they can influence treatment decisions and consent processes. This literature review examines the efficacy and controversies surrounding ECT in the management of TRD. Studies assessing the effectiveness of ECT in TRD, along with associated adverse effects and ethical considerations, are reviewed. Additionally, the role of ECT in contemporary psychiatric practice and its comparison with alternative treatments for TRD are discussed. The review highlights the complex interplay between clinical efficacy, safety, patient preferences, and societal perceptions in shaping the utilization of ECT in the treatment of TRD.

Real-world demographic and clinical profiles of patients with treatment-resistant depression initiated on esketamine nasal spray

Objective ESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch. Methods Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient’s care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program ‘Temporary Authorisation for Use’ (ATU), post-ATU, and post-launch cohorts. Results The overall ESKALE cohort (N = 160 included; n = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts. Conclusion These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine.

Describing the burden of disease amongst inpatients with treatment resistant major depressive disorder in Australia.

To describe the quality of life and clinical characteristics of treatment-resistant depression (TRD) patients in an Australian patient cohort recruited cross-sectionally during admission. Inpatients admitted for TRD treatment completed a quality of life questionnaire (AQoL-8D) and a depression severity assessment (HAM-D). A chart review and patient interview occurred for demographic and patient characteristics. Comparisons between the mean AQoL-8D scores of the study population and Australian population norms occurred. 79 TRD inpatients (70.9% female), mean age of 44.8 ± 14.9 years, were recruited, with 78.5% having an anxiety disorder, 48.1% post-traumatic stress disorder, and 30.4% a personality disorder. Adjunctive to antidepressants, 92.4% were taking antipsychotics and 55.7% were taking mood stabilisers. Approximately 42% of patients received transcranial magnetic stimulation, and 35.4% received electroconvulsive therapy. Mean HAM-D score was 20.3 ± 5.2, and AQoL-8D score (120.1 ± 16.5) was significantly higher than Australian population norms (p < .001) indicating reduced quality of life. Personal and clinical characteristics of patients hospitalised for TRD were similar to TRD globally with impaired quality of life relative to the general Australian population. TRD patients on average presented with moderate/severe depression, highlighting the need for greater support for these individuals.

Machine Learning-Driven Evaluation of Pramipexole and Aripiprazole as Augmentation Therapies in Treatment-Resistant Depression

Background Treatment-resistant depression (TRD) presents a significant clinical challenge, often requiring augmentation strategies. Pramipexole and aripiprazole are two such agents used to augment antidepressant therapy. However, their comparative efficacy remains under-researched. Objective This case report aims to evaluate the efficacy of pramipexole compared to aripiprazole as augmentation therapy in treatment-resistant depression. Methods Two patients with TRD were treated with pramipexole or aripiprazole augmentation. Clinical assessments were conducted using the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Severity (CGI-S), and the Beck Depression Inventory (BDI) before and after the treatment. Results Pramipexole showed greater efficacy in reducing depressive symptoms and improving overall functioning compared to aripiprazole. HDRS, CGI-S, and BDI scores decreased more significantly in the patient treated with pramipexole. Conclusion Pramipexole appears to be a more effective augmentation agent than aripiprazole in the treatment of TRD. These findings suggest pramipexole could be considered a preferred option for managing TRD.

Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.

Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants. To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program. A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment. The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy. ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.

Combination of Transcranial Magnetic Stimulation and Ketamine in Treatment-Resistant Depression: A Systematic Review.

Treatment-resistant depression (TRD) is a significant challenge in psychiatric practice, affecting a substantial proportion of patients with major depressive disorder (MDD). Traditional treatment modalities often fall short, necessitating the exploration of alternative therapies. This literature review examines the combined use of Transcranial Magnetic Stimulation (TMS) and ketamine in treating TRD. The objectiveof this study is toevaluate the efficacy, safety, and potential synergies of combining TMS and ketamine in the treatment of TRD. A comprehensive literature search was conducted using PubMed and Google Scholar databases from 2014 to 2024. The search terms included combinations of "Transcranial Magnetic Stimulation," "Ketamine," "Depression," "Major Depressive Disorder," "Treatment-Resistant Depression," and "Combination." After screening for relevance and applying inclusion and exclusion criteria, six studies were selected for review, including three case reports, a retrospective study, a pilot study, and a review study. The selected studies demonstrated that the combination of TMS and ketamine resulted in substantial and sustained improvement in depressive symptoms for patients with TRD. Case reports and retrospective studies highlighted significant reductions in depression severity and improvements in psychosocial functioning. The combination therapy showed a higher efficacy compared to monotherapies of either TMS or ketamine alone. Notably, adverse effects were generally mild and transient, with no severe adverse events reported in most studies. In conclusion, the combination of TMS and ketamine presents a promising treatment modality for patients with TRD, offering significant improvements in depressive symptoms and better outcomes compared to traditional monotherapies. However, the heterogeneity in study designs and small sample sizes underline the need for larger, randomized controlled trials to establish standardized protocols and further validate these findings.

Overcoming treatment-resistant depression with machine-learning based tools: a study protocol combining EEG and clinical data to personalize glutamatergic and brain stimulation interventions (SelecTool Project).

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD's clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool's recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.

Online mindfulness-based cognitive therapy for treatment-resistant depression: a parallel-arm randomized controlled feasibility trial.

Treatment-resistant depression (TRD) presents a significant challenge, affecting approximately 30% of individuals diagnosed with major depressive disorder and leading to poor treatment responses. Innovations in digital mental health, especially online mindfulness-based cognitive therapy (eMBCT), offer promising avenues for enhancing access to effective mental health care for individuals with TRD in a clinical setting. The aim of this study was to examine the feasibility of eMBCT in an individual clinical context to decrease depressive symptoms for TRD. Conducted at the Institute of Psychiatry of the Federal University of Rio de Janeiro, Brazil, this parallel-arm, randomized controlled feasibility trial involved outpatients diagnosed with TRD, aged 18 and above. Of the 39 outpatients invited, 28 were randomized into two groups: an intervention group receiving the eMBCT program (n = 15) and a control group (n = 13). The intervention, consisting of an 8-week course, was delivered via live video sessions. Following the assessment period, participants in the control group were offered the eMBCT intervention. Assessments using standardized questionnaires were conducted at the start and end of the study. Within the eMBCT group, improvements were observed in depression symptoms (Z = -3.423; p = 0.001; effect size r = 0.78), anxiety symptoms (Z = -3.361; p = 0.001; effect size r = 0.77), with no significant changes in the control group. Comparatively, the eMBCT group showed significant reductions in depression symptoms and improvements in clinical global impressions over the control group (BDI2: U = 30.5; p = 0.015; effect size r = 0.47, CGI1: U = 21.0; p = 0.004; effect size r = 0.56). eMBCT in an individual format combined with medication, appears to be a feasible treatment for TRD, decreasing symptoms of depression. In a future trial the control group may have a manualized intervention. The Brazilian Clinical Trials Registry: (https://ensaiosclinicos.gov.br/rg/RBR-6zndpbv) and RBR-6zndpbv.

A Systematic Review on Ketamine and Esketamine for Treatment-Resistant Depression and Suicidality in Adolescents: A New Hope?

Treating depression in adolescents is a significant challenge, and major depressive disorder (MDD) with suicidal ideation and treatment-resistant depression (TRD) are common and potentially devastating to optimal psychological and physical development in this age group. Suicide is among the leading causes of youth mortality, and TRD occurs in up to 40% of adolescents with MDD. TRD involves severe, persistent symptoms that are hard to treat, significantly reducing functioning and quality of life. We conducted a literature search focusing on key terms related to ketamine and esketamine for MDD with suicidal ideation and TRD in adolescents, aiming to review the potential utility of these molecules in adolescents for these conditions. Ketamine has shown efficacy in reducing depressive symptoms in adolescents with TRD. Esketamine has shown efficacy in reducing depressive symptoms and treating suicidal ideation in adolescents. Both ketamine and esketamine have demonstrated favorable safety and tolerability profiles. Using these drugs for serious conditions like adolescent MDD with suicidal thoughts and TRD can effectively treat symptoms, reduce self-harm and suicide risks, and provide a window for longer-term therapeutic interventions. The prompt and effective treatment of TRD could improve adolescents' quality of life. However, more research is needed to optimize treatment protocols and evaluate long-term effects.

Treatment-Resistant Depression and Medications

The management of treatment-resistant depression (TRD) is challenging. Researchers have identified novel targets, especially the glutamatergic system, in the pathogenesis of depressive disorder. N-methyl-D-aspartate (NMDA) receptor antagonists, like ketamine, have revolutionized the treatment of TRD due to their rapid antidepressant and antisuicidal effect. Various other receptor systems, including GABAergic, opioid receptors, the endogenous cannabinoid system, and cholinergic receptors, are novel targets to produce an antidepressant response. The US Food and Drug Administration (FDA) has approved intra-nasal ketamine as an add-on therapy to conventional antidepressants for TRD. Other compounds are in various stages of development. Identification and development of novel compounds by future research can help in overcoming the challenges of treating TRD. [ Psychiatr Ann . 2024;54(6):e177–e181.]

Dialectical Behavior Therapy as an intervention for Treatment Resistant Depression in adults: A protocol for systematic review and meta-analysis.

Major Depressive Disorder is a long-term, recurring, and very common illness that is associated with a significant decline in functional ability. The gold-standard method of treating depression is pharmacotherapy, which involves the use of antidepressant medications either alone or in various combinations. However, approximately 30% of Major Depressive Disorder patients suffer from Treatment Resistant Depression, a more severe condition that has a profound impact on patients' lives. Our study aims to conduct the first comprehensive review and meta-analysis to assess the effectiveness and safety of adding Dialectical Behavior Therapy to antidepressant medications compared to groups using pharmacotherapy alone as an intervention for adults with Treatment Resistant Depression. We will search for publications in the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Lilacs, Web of Science, and PsycINFO. We will manually review the reference lists of the included studies to identify potentially relevant studies. There will be no restrictions on the language or publication date. Quality assessment of the included studies will be performed independently according to the Cochrane Risk of Bias instrument. To assess the certainty of the findings' body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This study aims to determine the effectiveness and safety of Dialectical Behavior Therapy as an intervention for Treatment Resistant Depression in adults. Ethical approval was not required as individual patient data was not obtained. Our intention is to publish the systematic review in a medical journal that offers open access upon completion of the process. PROSPERO registration number CRD42023406301. Registered on March 24, 2023.

Is it now time to prepare psychiatry for a psychedelic future?

Australia has just rescheduled two drugs controlled under the United Nations Psychotropic Drug Conventions, psilocybin and MDMA, as treatments for treatment-resistant depression and post-traumatic stress disorder respectively. This feature explores the reasons for these developments, the opportunities and challenges they provide to psychiatry communities and how along with health systems these communities might respond to these developments.

Facts and myths about use of esketamine for treatment-resistant depression: a narrative clinical review.

Treatment-resistant depression (TRD) occurs when at least two different antidepressants, taken at the right dosage, for adequate period of time and with continuity, fail to give positive clinical effects. Esketamine, the S-enantiomer of ketamine, was recently approved for TRD treatment from U.S. Food and Drug Administration and European Medicine Agency. Despite proved clinical efficacy, many misconceptions by clinicians and patients accompany this medication. We aimed to review the most common "false myths" regarding TRD and esketemine, counterarguing with evidence-based facts. The keywords "esketamine", "treatment resistance depression", "depression", "myth", "mythology", "pharmacological treatment", and "misunderstanding" were entered in the main databases and combined through Boolean operators. Misconceptions regarding the TRD prevalence, clinical features and predictors have been found. With respect of esketamine, criteria to start treatment, dissociative symptoms, potential addiction and aspects of administration and monitoring, were found to be affected by false beliefs by clinicians and patients. TRD represents a challenging condition, requiring precise diagnosis in order to achieve patient's full recovery. Esketamine has been proved as an effective medication to treat TRD, although it requires precautions. Evidence can inform clinical practice, in order to offer this innovative treatment to all patients with TRD.

Gender differences in the therapeutic response to lifestyle improvement-based interventions for treatment-resistant depression

Treatment-resistant depression (TRD) poses a significant societal challenge, with gender-specific treatment gaps. In a clinical trial targeting TRD, we introduced lifestyle-based interventions. Analyzing data from 24 men and 70 women with TRD, the current study aimed to assess gender-related efficacy differences. Descriptive and univariate analyses unveiled variations in sociodemographic and clinical factors. Utilizing repeated measures ANOVA while controlling for baseline values and age, results indicated a notable gender disparity. Specifically, women exhibited a significantly poorer progression of depressive symptoms. This underscores the need for tailored interventions addressing gender-specific nuances in TRD treatment.

Negative association between basal oxytocin and oxytocin changes after repetitive transcranial magnetic stimulation in patients with treatment-resistant depression

Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulator effective for treating depressive symptoms in patients with treatment-resistant depression (TRD). One of the multiple mechanisms for its antidepressant effects proposed is related to the hypothalamus. Oxytocin is a neuropeptide synthesized in the hypothalamus that affects human behavior and psychology, including social and affiliative behaviors, stress regulation, and fear and emotion processing. There have been no reports on the relationship between rTMS and oxytocin for the treatment of TRD. Therefore, we aimed to investigate changes in salivary oxytocin concentrations in patients with TRD before and after 6 weeks of rTMS treatment. A total of 28 patients with TRD who received rTMS at Saga University Hospital between August 2013 and August 2020 were included. Although rTMS treatment significantly improved 24-item Hamilton Depression Rating Scale scores, rTMS treatment did not change mean salivary oxytocin after 6 weeks of treatment in patients with TRD. Multiple regression analysis revealed that the change in salivary oxytocin levels after rTMS treatment was negatively associated with basal oxytocin levels before rTMS treatment, suggesting that rTMS treatment tends to decrease oxytocin levels in patients with depression with high basal oxytocin levels while increasing them in those with low basal levels. These findings suggest that rTMS treatment improved depressive symptoms through mechanisms other than the modulatory effect on oxytocin levels in patients with TRD, while there is room for further studies to confirm these findings using a larger patient sample size and/or a sham rTMS procedure.

Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.

(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.