Deep transcranial magnetic stimulation for schizophrenia: a systematic review.

Background: The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia. Methods: A systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted. Results: Three randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10). Conclusion: This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings.

Narrative Review and Consensus Recommendations for the Use of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange in Modified Electroconvulsive Therapy.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a safe, effective, and novel technique that is currently being used in electroconvulsive therapy (ECT). This study aimed to summarize the clinical practices of THRIVE use in ECT to aid physicians and institutions in implementing the best practice guidelines for ECT. Thus, we reviewed the current literature and presented our consensus on the application of THRIVE in ECT in daily clinical practice. This consensus provides information regarding THRIVE use in ECT, including its safety, effectiveness, procedures, precautions, special case management, and application in special populations. Moreover, it guides the standardized use of THRIVE in ECT.

Sex Differences in the Antidepressant and Neurocognitive Effects of Nonconvulsive Electrotherapy in Patients with Treatment-Refractory Depression.

Objective: The objective of this study was to examine sex differences in the antidepressant and neurocognitive effects of adjunctive nonconvulsive electrotherapy (NET) in patients with treatment-refractory depression (TRD), which has not yet been thoroughly investigated. Methods: The study enrolled 20 patients with TRD, comprising 11 males and 9 females, who underwent a series of 6 NET sessions. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess depressive symptoms, response, and remission at baseline and after the first, third, and sixth NET sessions. The Wisconsin Card Sorting Test (WCST) was used to assess neurocognitive function at baseline and after the sixth NET session. Results: After completing 6 NET sessions, female patients experiencing TRD exhibited a higher inclination toward achieving an antidepressant response (77.8% vs. 45.5%, P = .197) and antidepressant remission (22.2% vs. 0%, P = .189) when compared to their male counterparts. No significant differences were observed in changes in the HAMD-17 and WCST subscale scores (all P > .05), including completing classification number, total error number, persistent error number, and random error number between males and females. Additionally, no significant correlations were observed between baseline WCST subscale scores and changes in HAMD-17 scores or endpoint scores, irrespective of sex (all P > .05). Conclusion: These pilot findings suggest that female patients with TRD exhibited increased rates of achieving antidepressant response and remission after undergoing NET. However, further studies should be conducted to confirm these findings.

Deep transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis of randomized controlled studies.

The efficacy and safety of deep transcranial magnetic stimulation (dTMS) in treating treatment-resistant depression (TRD) are unknown. Up to June 21, 2023, we conducted a systematic search for RCTs, and then extracted and synthesized data using random effects models. Five RCTs involving 507 patients with TRD (243 in the active dTMS group and 264 in the control group) were included in the present study. The active dTMS group showed significantly higher study-defined response rate (45.3% versus 24.2%, n = 507, risk ratio [RR] = 1.87, 95% confidence interval [CI]: 1.21-2.91, I2 = 53%; P = 0.005) and study-defined remission rate (38.3% versus 14.4%, n = 507, RR = 2.37, 95%CI: 1.30-4.32, I2 = 58%; P = 0.005) and superiority in improving depressive symptoms (n = 507, standardized mean difference = -0.65, 95%CI: -1.11--0.18, I2 = 82%; P = 0.006) than the control group. In terms of cognitive functions, no significant differences were observed between the two groups. The two groups also showed similar rates of other adverse events and all-cause discontinuations (P > 0.05). dTMS is an effective and safe treatment strategy for the management of patients with TRD.

Bilateral theta burst stimulation for patients with acute unipolar or bipolar depressive episodes: A systematic review of randomized controlled studies.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluated the overall efficacy and safety of bilateral theta-burst stimulation (TBS) as an intervention for patients with mood disorders. METHODS: A systematic search (up to December 7, 2022) of RCTs was conducted to address the study aims. A random-effects meta-analysis was performed by including study-defined responses and remission as primary outcomes. RESULTS: Analyses included six RCTs comprising 285 participants with major depressive disorder (MDD) (n = 233) or a depressive episode in the course of bipolar disorder (BD) (n = 52) who had undergone active bilateral TBS (n = 142) versus sham stimulation (n = 143). Active bilateral TBS outperformed sham stimulation with respect to study-defined improvements (55.1 % versus 20.3 %, 4 RCTs, n = 152, 95%CI: 1.63 to 4.39, P < 0.0001; I2 = 0 %) and remission rates (37.2 % versus 14.3 %, 2 RCTs, n = 85, 95%CI: 1.13 to 5.95, P = 0.02; I2 = 0 %) in MDD patients but not those with bipolar or unipolar mixed depression. Superiority of active bilateral TBS over sham stimulation was confirmed for improvements in depressive symptoms at post-bilateral TBS assessments and 8-week follow-ups in patients with either MDD or mixed depression (all P < 0.05). Discontinuation rates due to any reason and adverse events (i.e., headache, dizziness) were similar between TBS and sham stimulation groups with MDD or mixed depression (all P > 0.05). CONCLUSION: Bilateral TBS targeting the dorsolateral prefrontal cortex (DLPFC) appears to be a well-tolerated form of repetitive transcranial magnetic stimulation (rTMS) that has substantial antidepressant effects, particularly in patients with MDD. Effects of bilateral TBS on bipolar and unipolar mixed depression should be further investigated.

Adjunctive repetitive transcranial magnetic stimulation for adolescents with first-episode major depressive disorder: a meta-analysis.

Objective: This meta-analysis of randomized clinical trials (RCTs) was conducted to explore the therapeutic effects, tolerability and safety of repetitive transcranial magnetic stimulation (rTMS) as an adjunct treatment in adolescents with first-episode major depressive disorder (FE-MDD). Methods: RCTs examining the efficacy, tolerability and safety of adjunctive rTMS for adolescents with FE-MDD were included. Data were extracted by three independent authors and synthesized using RevMan 5.3 software with a random effects model. Results: A total of six RCTs involving 562 adolescents with FE-MDD were included. Adjunctive rTMS was superior in improving depressive symptoms over the control group [standardized mean difference (SMD) = -1.50, 95% confidence interval (CI): -2.16, -0.84; I2 = 89%, p < 0.00001] in adolescents with FE-MDD. A sensitivity analysis and two subgroup analyses also confirmed the significant findings. Adolescents with FE-MDD treated with rTMS had significantly greater response [risk ratio (RR) = 1.35, 95% CI: 1.04, 1.76; I2 = 56%, p = 0.03] and remission (RR = 1.35, 95% CI: 1.03, 1.77; I2 = 0%, p = 0.03) over the control group. All-cause discontinuations were similar between the two groups (RR = 0.79, 95% CI: 0.32, 1.93; I2 = 0%, p = 0.60). No significant differences were found regarding adverse events, including headache, loss of appetite, dizziness and nausea (p = 0.14-0.82). Four out of six RCTs (66.7%), showed that adjunctive rTMS was more efficacious over the control group in improving neurocognitive function (all p < 0.05). Conclusion: Adjunctive rTMS appears to be a beneficial strategy in improving depressive symptoms and neurocognitive function in adolescents with FE-MDD. Higher quality RCTs with larger sample sizes and longer follow-up periods are warranted in the future.

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review.

Objective: Intermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment-resistant depression (TRD). Methods: Randomized controlled trials (RCTs) comparing the efficacy and safety of iTBS and HF-rTMS were identified by searching English and Chinese databases. The primary outcomes were study-defined response and remission. Results: Two RCTs (n = 474) investigating the efficacy and safety of adjunctive iTBS (n = 239) versus HF-rTMS (n = 235) for adult patients with TRD met the inclusion criteria. Among the two included studies (Jadad score = 5), all were classified as high quality. No group differences were found regarding the overall rates of response (iTBS group: 48.0% versus HF-rTMS group: 45.5%) and remission (iTBS group: 30.0% versus HF-rTMS group: 25.2%; all Ps > 0.05). The rates of discontinuation and adverse events such as headache were similar between the two groups (all Ps > 0.05). Conclusion: The antidepressant effects and safety of iTBS and HF-rTMS appeared to be similar for patients with TRD, although additional RCTs with rigorous methodology are needed.

Accelerated intermittent theta burst stimulation for major depressive disorder or bipolar depression: A systematic review and meta-analysis.

We aimed to systematically evaluate the clinical efficacy and safety of accelerated intermittent theta burst stimulation (aiTBS) for patients with major depressive disorder (MDD) or bipolar depression (BD). A random-effects model was adopted to analyze the primary and secondary outcomes using the Review Manager, Version 5.3 software. This meta-analysis (MA) identified five double-blind randomized controlled trials (RCTs) comprising 239 MDD or BD patients with a major depressive episode. Active aiTBS overperformed sham stimulation in the study-defined response. This MA found preliminary evidence that active aiTBS resulted in a greater response in treating major depressive episodes in MDD or BD patients than sham stimulation.

Adjunctive transcranial alternating current stimulation for patients with major depressive disorder: A systematic review and meta-analysis.

Objective: We performed a meta-analysis of randomized, double-blind, controlled trials (RCTs) to systematically investigate the therapeutic effects and tolerability of transcranial alternating current stimulation (tACS) for the treatment of patients with major depressive disorder (MDD). Methods: Electronic search of PubMed, PsycINFO, EMBASE, Chinese National Knowledge Infrastructure, Wanfang database, and the Cochrane Library up to 1 April 2022. Double-blind RCTs examining the efficacy and safety of tACS for patients with MDD were included. The primary outcome was the improvement of depressive symptoms following a course of tACS treatment. Data were analyzed using Review Manager Version 5.3 (Cochrane IMS, Oxford, UK). Study quality was assessed using the Cochrane risk of bias and Jadad scale. Publication bias was assessed using a funnel plot and the Egger test. Results: We identified 883 articles, of which 4 RCTs with 5 active treatment arms covering 224 participants with MDD on active tACS (n = 117) and sham tACS (n = 107) were eligible for inclusion. Meta-analysis of depressive symptoms at post-tACS found an advantage of active tACS over sham tACS (n = 212, standard mean difference (SMD) = -1.14, 95% confidence interval (CI): -2.23, -0.06; I 2 = 90%, P = 0.04). The significant superiority of active tACS over sham tACS in improving depressive symptoms remained in a sensitivity analysis. Active tACS was significantly superior to sham tACS regarding depressive symptoms at the 4 week follow-up (SMD = -1.07, 95% CI: -2.05, -0.08; I 2 = 88%, P = 0.03) and study-defined remission [risk ratio (RR) = 2.07, 95% CI: 1.36, 3.14, I 2 = 9%, P = 0.0006]. The discontinuation rate due to any reason was similar between the two groups (P > 0.05). All included studies were rated as high quality (Jadad score ≥ 3), with funnel plots of primary outcome not suggestive of publication bias. Conclusion: tACS appeared to be modestly effective and safe for improving depressive symptoms in patients with MDD, although further studies are warranted.

Electroconvulsive therapy knowledge and attitudes among patients and caregivers in South China: A preliminary study.

Background: Electroconvulsive therapy (ECT) is a safe and effective therapy for individuals suffering from major psychiatric disorders, but attitudes towards ECT among patients and caregivers have not been well studied. This study was conducted to elucidate patient and caregiver knowledge and attitudes concerning ECT in South China. Methods: The sample comprised 92 patients diagnosed with major psychiatric disorders and their caregivers (n = 92). Participants completed questionnaire measures of knowledge and attitudes related to ECT. Results: Information before ECT was inadequately provided to both caregivers and patients (55.4% versus 37.0%, p < 0.05). Caregivers reported receiving more adequate information about the therapeutic effects (50.0% versus 44.6%), side effects (67.4% versus 41.3%), and risks (55.4% versus 20.7%) of ECT when compared to patients (all p < 0.05). However, less than half of patients and caregivers believed that ECT was effective (43.5% versus 46.7%, p > 0.05), while more than half of them believed that ECT was beneficial (53.3% versus 71.7%, p < 0.05), and approximately half of them believed that ECT was safe (50.0% versus 51.1%, p > 0.05). A total of 32.6% of patients and 55.4% of caregivers (p < 0.05) reported that ECT was used only for critically ill patients. A total of 62.0% of patients experienced side effects, with memory impairment being the most commonly reported. Conclusion: Clinicians should develop a systematic health education program before ECT treatment and ensure that patients and caregivers have an accurate understanding of ECT, particularly the treatment process, its therapeutic effects and potential side effects prior to administering this treatment.

Comparison of Efficacy and Safety of Magnetic Seizure Therapy and Electroconvulsive Therapy for Depression: A Systematic Review.

OBJECTIVES: As a new physical therapeutic technique, magnetic seizure therapy (MST) has established efficacy in the treatment of depression with few cognitive side effects, and thus appears to be a potential alternative to electroconvulsive therapy (ECT). The findings of randomized controlled trials (RCTs) examining the efficacy and safety of MST versus ECT for depression are inconsistent. This systematic review of RCTs was designed with the aim of assessing the safety and efficacy of MST versus ECT for patients with depression. METHODS: The WanFang, Chinese Journal Net (CNKI), EMBASE, PubMed, Cochrane Library, and PsycINFO databases were systematically searched by three independent investigators, from their inceptions to July 24, 2021. RESULTS: In total, four RCTs (n = 86) were included and analyzed. Meta-analyses of study-defined response (risk ratio (RR) = 1.36; 95% CI = 0.78 to 2.36; p = 0.28; I2 = 0%), study-defined remission (RR = 1.17; 95% CI = 0.61 to 2.23; p = 0.64; I2 = 0%), and the improvement in depressive symptoms (standardized mean difference (SMD) = 0.21; 95% CI = -0.29 to 0.71; p = 0.42; I2 = 0%) did not present significant differences between MST and ECT. Three RCTs evaluated the cognitive effects of MST compared with ECT using different cognitive measuring tools, but with mixed findings. Only two RCTs reported adverse drug reactions (ADRs), but these lacked specific data. Only one RCT reported discontinuation due to any reason. CONCLUSIONS: This preliminary study suggests that MST appears to have a similar antidepressant effect as ECT for depression, but mixed findings on adverse cognitive effects were reported.

Transcranial alternating current stimulation for schizophrenia: a systematic review of randomized controlled studies.

Background: In randomized clinical trials (RCTs) investigating the application of transcranial alternating current stimulation (tACS) in schizophrenia, inconsistent results have been reported. The purpose of this exploratory systematic review of RCTs was to evaluate tACS as an adjunct treatment for patients with schizophrenia based on its therapeutic effects, tolerability, and safety. Methods: Our analysis included RCTs that evaluated adjunctive tACS' effectiveness, tolerability, and safety in schizophrenia patients. Three independent authors extracted data and synthesized it using RevMan 5.3 software. Results: Three RCTs involving 76 patients with schizophrenia were encompassed in the analysis, with 40 participants receiving active tACS and 36 receiving sham tACS. Our study revealed a significant superiority of active tACS over sham tACS in improving total psychopathology (standardized mean difference [SMD] = -0.61, 95% confidence interval [CI]: -1.12, -0.10; I2 = 16%, p = 0.02) and negative psychopathology (SMD = -0.65, 95% CI: -1.11, -0.18; I2 = 0%, p = 0.007) in schizophrenia. The two groups, however, showed no significant differences in positive psychopathology, general psychopathology, or auditory hallucinations (all p > 0.05). Two RCTs examined the neurocognitive effects of tACS, yielding varied findings. Both groups demonstrated similar rates of discontinuation due to any reason and adverse events (all p > 0.05). Conclusion: Adjunctive tACS is promising as a viable approach for mitigating total and negative psychopathology in individuals diagnosed with schizophrenia. However, to gain a more comprehensive understanding of tACS's therapeutic effects in schizophrenia, it is imperative to conduct extensive, meticulously planned, and well-documented RCTs.

Adjunctive accelerated repetitive transcranial magnetic stimulation for older patients with depression: A systematic review.

Objective: We performed this systemic review to investigate the therapeutic potential and safety of adjunctive accelerated repetitive transcranial magnetic stimulation (aTMS) for older patients with depression. Methods: We included published randomized clinical trials (RCTs) and observational studies targeting adjunctive aTMS for older patients with depression. Results: Two open-label self-controlled studies (n = 29) fulfilled the criteria for inclusion. The included studies reported significant improvements in depressive symptoms from baseline to post-aTMS (all Ps < 0.05). One study reported a dropout rate of 10.5% (2/19). Mild headache was the most common adverse reaction. Conclusion: The currently available evidence from two open-label self-controlled studies indicates that adjunctive aTMS is a safe and effective therapy for older patients with depression.

Adjunctive Magnetic Seizure Therapy for Schizophrenia: A Systematic Review.

Objective: The efficacy and safety of adjunctive magnetic seizure therapy (MST) for patients with schizophrenia are unclear. This systematic review was conducted to examine the efficacy and safety of adjunctive MST for schizophrenia. Methods: Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO, and the Cochrane Library) databases were systematically searched. Results: Two open-label self-controlled studies (n = 16) were included and analyzed in this review. In these studies, the Positive and Negative Syndrome Scale (PANSS) total scores and Brief Psychiatric Rating Scale (BPRS) total scores significantly decreased from baseline to post-MST (all Ps < 0.05), without serious adverse neurocognitive effects. Mixed findings on the neurocognitive effects of adjunctive MST for schizophrenia were reported in the two studies. A discontinuation rate of treatment of up to 50% (4/8) was reported in both studies. The rate of adverse drug reactions (ADRs) was evaluated in only one study, where the most common ADRs were found to be dizziness (25%, 2/8) and subjective memory loss (12.5%, 1/8). Conclusion: There is inconsistent evidence for MST-related adverse neurocognitive effects and preliminary evidence for the alleviation of psychotic symptoms in schizophrenia.

BDNF and the Antidepressant Effects of Ketamine and Propofol in Electroconvulsive Therapy: A Preliminary Study.

OBJECTIVE: Ketamine and propofol have become increasingly popular in electroconvulsive therapy (ECT) anaesthesia. This study was conducted to examine whether changes in serum levels of brain-derived neurotrophic factor (BDNF) are associated with the antidepressant effects of ketofol, a combination of ketamine and propofol, in ECT for patients with treatment-resistant depression (TRD). METHODS: Thirty patients with TRD (18-65 years) were enrolled and underwent eight ECT sessions with ketamine (0.5 mg/kg) plus propofol (0.5 mg/kg) (ketofol). Symptom severity was monitored using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Brief Psychiatric Rating Scale (BPRS), and serum levels of BDNF were examined by enzyme-linked immunosorbent assay (ELISA) at baseline and after 2, 4, and 8 ECT treatments. Serum levels of BDNF were also collected from thirty healthy controls. RESULTS: At baseline, there were no significant differences in serum levels of BDNF between patients with TRD and healthy controls. The response and remission rates in patients with TRD were 100% (30/30) and 53.3% (16/30) after ECT treatment, respectively. Despite a significant reduction in HAMD-17 and BPRS scores after ECT, no changes in serum levels of BDNF were observed after ECT treatment when compared to baseline. No association was found between serum levels of BDNF and changes in illness severity. CONCLUSION: Serum levels of BDNF did not represent a suitable candidate biomarker for determining the antidepressant effects of ketofol during ECT for patients with TRD.

Sex Differences in the Prevalence and Clinical Features of Comorbid Depressive Symptoms in Never-Treated Chinese Patients With First-Episode Schizophrenia.

BACKGROUND: Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet. METHODS: Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015. RESULTS: The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²1 = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (ß = 0.75, t = 7.72, P < .001) and total score (ß = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (ß = 0.74, t = 8.45, P < .001), total score (ß = 0.47, t = 5.71, P < .001), and cognitive factor subscore (ß = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score. CONCLUSIONS: Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients.