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ObjectivesThe purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD).MethodsA systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs).ResultsFive RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2–13%) and the control group (4–21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache.ConclusionPsilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs.

BackgroundThe 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.MethodsA systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted.ResultsThree 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).ConclusionThis 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.

BackgroundIn 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.MethodsOur 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.ResultsThree 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).ConclusionAdjunctive 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.

ObjectiveThis 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).MethodsRCTs 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.ResultsA 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

ObjectiveThis systematic review of randomized controlled trials (RCTs) was conducted to explore the therapeutic effects and safety of active low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) versus sham LF-rTMS in children and adolescent patients with first-episode and drug-naïve (FEDN) major depressive disorder (MDD).MethodsA systematic literature search was performed, and data were extracted by two independent researchers. The coprimary outcomes were study-defined response and remission.ResultsA systematic search of the literature yielded 442 references, of which 3 RCTs (130 children and adolescents with FEDN MDD, 50.8% male, and mean age range from 14.5 to 17.5 years) met the inclusion criteria. Among the two RCTs (66.7%, 2/3) examining the effects of LF-rTMS on study-defined response and remission and cognitive function, active LF-rTMS was more efficacious than sham LF-rTMS in terms of study-defined response rate and cognitive function (all p 0.05). No significant group differences were found with regard to adverse reactions. None of the included RCTs reported the dropout rate.ConclusionThese findings preliminarily found that LF-rTMS could benefit children and adolescents with FEDN MDD in a relatively safe manner, although further studies are warranted.

Background The use of ketamine in electroconvulsive therapy (ECT) has been examined in the treatment of major depressive disorder (MDD); however, there has been no systematic review and meta-analysis of related randomised controlled trials (RCTs).Aim To examine the efficacy and safety of ketamine augmentation of ECT in MDD treatment.Methods Two reviewers searched Chinese (China National Knowledge Infrastructure and Wanfang) and English (PubMed, PsycINFO, Embase and Cochrane Library) databases from their inception to 23 July 2019. The included studies' bias risk was evaluated using the Cochrane risk of bias assessment tool. The primary outcome of this meta-analysis was improved depressive symptoms at day 1 after a single ECT treatment session. Data were pooled to calculate the standardised mean difference and risk ratio with their 95% CIs using RevMan V.5.3. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the whole quality of evidence.Results Four RCTs (n = 239) compared ketamine alone or ketamine plus propofol (n = 149) versus propofol alone (n = 90) in patients with MDD who underwent a single ECT session. Three RCTs were considered as unclear risk with respect to random sequence generation using the Cochrane risk of bias. Compared with propofol alone, ketamine alone and the combination of ketamine and propofol had greater efficacy in the treatment of depressive symptoms at days 1, 3 and 7 after a single ECT session. Moreover, compared with propofol alone, ketamine alone and the combination of ketamine and propofol were significantly associated with increased seizure duration and seizure energy index. Compared with propofol, ketamine alone was significantly associated with increased opening-eye time. Based on the GRADE approach, the evidence level of primary and secondary outcomes ranged from very low (26.7%, 4/15) to ‘low’ (73.3%, 11/15).Conclusion Compared with propofol, there were very low or low evidence levels showing that ketamine alone and the combination of ketamine and propofol appeared to rapidly improve depressive symptoms of patients with MDD undergoing a single ECT session. There is a need for high-quality RCTs.

Background Hyperprolactinaemia is a common adverse effect of antipsychotics (APs). The results of Peony-Glycyrrhiza decoction (PGD) as a potentially useful adjunctive treatment for hyperprolactinaemia are inconsistent.Aim This meta-analysis of randomised controlled trials (RCTs) examined the efficacy and safety of adjunctive PGD therapy for AP-induced hyperprolactinaemia.Methods English (PubMed, Embase, Cochrane Library, PsycINFO) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data) databases were systematically searched up to 10 June 2018. The inclusion criteria were based on PICOS—Participants: adult patients with schizophrenia; Intervention: PGD plus APs; Comparison: APs plus placebo or AP monotherapy; Outcomes: efficacy and safety; Study design: RCTs. The weighted mean difference (WMD) and risk ratio (RR) along with their 95% CIs were calculated using Review Manager (RevMan) V.5.3 software.Results Five RCTs (n=450) were included and analysed. Two RCTs (n=140) were double-blind and four RCTs (n=409) reported ‘random’ assignment with specific description. The PGD group showed a significantly lower serum prolactin level at endpoint than the control group (n=380, WMD: −32.69 ng/mL (95% CI −41.66 to 23.72), p

Background: Hyperprolactinaemia is a common adverse effect of antipsychotics (APs). The results of Peony- Glycyrrhiza decoction (PGD) as a potentially useful adjunctive treatment for hyperprolactinaemia are inconsistent. Aim: This meta-analysis of randomised controlled trials (RCTs) examined the efficacy and safety of adjunctive PGD therapy for AP-induced hyperprolactinaemia. Methods: English (PubMed, Embase, Cochrane Library, PsycINFO) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data) databases were systematically searched up to 10 June 2018. The inclusion criteria were based on PICOS--Participants: adult patients with schizophrenia; Intervention: PGD plus APs; Comparison: APs plus placebo or AP monotherapy; Outcomes: efficacy and safety; Study design: RCTs. The weighted mean difference (WMD) and risk ratio (RR) along with their 95% CIs were calculated using Review Manager (RevMan) V.5.3 software. Results: Five RCTs (n=450) were included and analysed. Two RCTs (n=140) were double-blind and four RCTs (n=409) reported 'random' assignment with specific description. The PGD group showed a significantly lower serum prolactin level at endpoint than the control group (n=380, WMD: -32.69 ng/mL (95% CI -41.66 to 23.72), p<0.00001, I²=97%). Similarly, the superiority of PGD over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale (n=403, WMD: -0.62 (95% CI -2.38 to 1.15), p=0.49, I²=0%). There were similar rates of all-cause discontinuation (n=330, RR 0.93 (95% CI 0.63 to 1.37), p=0.71, I²=0%) and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from 'very low' (14.3%), 'low' (42.8%), 'moderate' (14.3%), to 'high' (28.6%). Conclusions: Current evidence supports the adjunctive use of PGD to suppress elevated prolactin and improve prolactininduced symptoms without significant adverse events in adult patients with AP-induced hyperprolactinaemia. Highquality RCTs with longer duration are needed to confirm these findings. [ABSTRACT FROM AUTHOR]