Effects of Acupuncture Therapy Combined with Conventional Western Medicine on Auditory Hallucination Symptoms, Mental Health, and Monoamine-Related Biomarkers in Patients with Chronic Auditory Hallucinations in Schizophrenia

Background: Several studies reported on the effectiveness of 1 Hz repeated transcranial magnetic stimulation (rTMS) over the temporoparietal cortex (TPC) on refractory auditory hallucinations (AH) in schizophrenia but little is known about the long-term therapeutic effect of this tool. Aim: The aim of this study was to evaluate rTMS’ impact on auditory hallucinations (AH) and cognitive functions in patients with schizophrenia with a three-month follow-up. Methods: In a randomized double blind sham controlled study, 26 patients with refractory schizophrenia received 1 Hz rTMS applied on TPC for four weeks. rTMS was given to patients over one month with five rTMS sessions each week. Patients were evaluated via AHRS (Auditory Hallucination Rating Scale, Hoffman et al.), PANSS (Positive and Negative Syndrome Scale, Kay et al. 1988), and CGI (Clinical Global Impression) before treatment by rTMS every week during the first month, and every month until the third month. Results: Neither clinical nor cognitive differences were found between rTMS and placebo. Conclusion: 1 Hz rTMS using parameters mentioned above has no statistically significant effect on AH; although evidences about the potential benefit of rTMS in the treatment of AH negative results suggest the need for further studies in this area.

Background:Transcranial direct current stimulation (tDCS) has demonstrated efficacy against antipsychotic-refractory auditory verbal hallucinations (AVH) in schizophrenia. The duration of persistence of benefit is not well characterized.Materials and Methods:Thirty-one adults with schizophrenia and medication-refractory AVH were treated with 2–3 mA tDCS in 30 min sessions, twice a day, 6 days a week, for 2–4 weeks. The anode was sited over F3 and the cathode midway between T3 and P3 in the 10–20 EEG system. Patients were assessed until a 4-month study endpoint using two auditory hallucination rating scales and the Positive and Negative Syndrome Scale (PANSS-N).Results:Auditory hallucinations were moderately reduced by tDCS with 25%–29% improvement evident by the end of the 2nd week and another 10% improvement between week 2 and 4 months. There was no loss of benefit at the end of the 4-month study. There was also a small (11%) but statistically significant improvement in PANSS-N scores.Conclusions:Although this study is limited by the nonblind, uncontrolled design, the results suggest that tDCS, as delivered, holds promise for treating refractory AVH in schizophrenia; the benefits persist beyond the short term.

Introduction A growing body of evidence supports the use of cognitive behavioral therapy (CBT) for the treatment of schizophrenia. Auditory hallucinations are a common feature in schizophrenia that persists as a distressing symptom even after adequate pharmacotherapy regimen. Combining pharmacotherapy with brief CBT may reduce the severity of symptoms through decreasing the distress caused by the hallucinations. Aim The aim of this study was to evaluate the effectiveness of brief individual CBT for auditory hallucinations combined with treatment as usual (TAU) compared with TAU only in a sample of Egyptian schizophrenic patients referred to the Outpatient Clinic of El Hadara University Hospital. Patients and methods A total of 40 patients diagnosed with schizophrenia referred to the outpatient clinic of El Hadara University Hospital were randomly assigned into two groups: group I received brief CBT for auditory hallucinations combined with TAU, and group II received TAU only. Brief CBT for auditory hallucinations was delivered on eight sessions of 45 min each with a frequency of once per week. Positive and Negative Syndrome Scale (PANSS) was assessed before and after therapy in both groups and outcome was compared. Results On comparing the pre-assessment scores with the post-assessment scores of group I after 8 weeks of brief CBT for auditory hallucinations, a significant symptom reduction was observed for the PANSS positive (−18.31%, P < 0.001), negative (−16.67%, P < 0.001), general symptoms (−16.53%, P < 0.001), and total (−16.53%, P < 0.001) scores. Moreover, on comparing group I with group II after 8 weeks of brief CBT for auditory hallucinations, a significant symptom reduction was observed for the PANSS positive (P < 0.001), negative (P = 0.008), general symptoms (P < 0.001), and total (P < 0.001) scores. Conclusion Brief CBT for auditory hallucinations was found to be effective in reducing symptom severity in schizophrenia

Treatment of nonresponsive auditory hallucinations in schizophrenia have been reported to improve with transcranial direct-current stimulation. This case description illustrates the use of add-on transcranial direct-current stimulation for rapid amelioration of auditory hallucinations in schizophrenia during the acute phase. Because transcranial direct-current stimulation is safe, largely well tolerated, and relatively inexpensive, this add-on treatment option is worth exploring through further rigorous studies.

Adjunctive tDCS for treatment-refractory auditory hallucinations in schizophrenia: A meta-analysis of randomized, double-blinded, sham-controlled studies.

Glutamate as a mediating transmitter for auditory hallucinations in schizophrenia: A 1H MRS study

Efficacy of repetitive transcranial magnetic stimulation on auditory hallucinations in schizophrenia: A meta-analysis

Purpose of reviewTo provide recent evidence on real-time neurofeedback (NFB) training for auditory verbal hallucinations (AVH) in schizophrenia patients.Recent findingsNFB is a promising technique that allows patients to gain control over their AVH by modulating their own speech-related/language-related networks including superior temporal gyrus (STG) and anterior cingulate cortex (ACC) using fMRI, fNIRS and EEG/MEG. A recent limited number of studies showed that while an EEG-based NFB study failed to regulate auditory-evoked potentials and reduce AVH, downregulation of STG hyperactivity and upregulation of ACC activity with fMRI-based NFB appear to alleviate treatment-resistant AVH in schizophrenia patients. A deeper understanding of AVH and development of more effective methodologies are still needed.SummaryDespite recent innovations in antipsychotics, many schizophrenia patients continue to suffer from treatment-resistant AVH and social dysfunctions. Recent studies suggested that real-time NFB shows promise in enabling patients to gain control over AVH by regulating their own speech-related/language-related networks. Although fMRI-NFB is suitable for regulating localized activity, EEG/MEG-NFB are ideal for regulating the ever-changing AVH. Although there are still many challenges including logistic complexity and burden on patients, we hope that such innovative real-time NFB trainings will help patients to alleviate severe symptoms and improve social functioning.

How increasing the effect of rTMS in the treatment of auditory hallucinations in schizophrenia?

Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD:-0.45 (95%CI: -1.01, 0.12), P = 0.13; I2=61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2=47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

High-definition transcranial direct current simulation (HD-tDCS) for persistent auditory hallucinations in schizophrenia.

Through imaging studies, a significant increase in cerebral activity has been detected in fronto-temporal areas in patients experiencing auditory verbal hallucinations. Therefore, non-invasive neuromodulation, in particular transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), has been considered as a therapeutic intervention for medication-resistant auditory verbal hallucinations in schizophrenia. We aimed to synthesize results from randomized trials on either rTMS or tDCS versus placebo in patients with schizophrenia by including five recently published trials in the field. A systematic review and meta-analysis of relevant literature was conducted. Studies were included on the basis of pre-defined selection criteria. The quality of the studies was assessed by the Cochrane Risk of Bias Tool for Randomized Controlled Trials. RevMan 5.3 was used to conduct the statistical analysis. Including 465 and 960 patients, respectively, 12 tDCS and 27 rTMS studies were included. Regarding treatment of medication refractory auditory verbal hallucinations, no significant effect of tDCS (−0.23 [-0.49, 0.02], p = 0.08) or rTMS (−0.19 [-0.50, 0,11], p = 0.21) was found compared to sham in this meta-analysis. The current study found that it cannot be concluded that rTMS and tDCS are efficacious in treating medication-resistant auditory verbal hallucinations. Larger randomized controlled tDCS trials of a higher quality should be conducted in the future to establish substantial evidence of tDCS. The interventions appear safe and may have beneficial effects on other outcomes.

Randomized trial of transcranial alternating current stimulation for treatment of auditory hallucinations in schizophrenia

Schizophrenia is a chronic psychiatric condition with complex symptomatology, including debilitating auditory hallucinations. Transcranial direct current stimulation (tDCS) has been explored as an adjunctive treatment to alleviate such symptoms. To evaluate the therapeutic efficacy of tDCS in schizophrenia. Adhering to PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, and the Cochrane Library on September 19, 2023, for randomized controlled trials examining the efficacy of tDCS in schizophrenia, with no language or time restrictions. We included studies that compared tDCS with a control condition and reported clinically relevant outcomes. Data extraction and quality assessments were performed by independent evaluators using the Cochrane Collaboration's risk of bias tool. Statistical heterogeneity was evaluated, and a random-effects model was applied due to moderate heterogeneity (I 2 = 41.3%). Nine studies comprising 425 participants (tDCS group: 219, control group: 206) were included. The meta-analysis demonstrated a significant reduction in auditory hallucination scores following tDCS treatment (weighted mean difference: -2.18, 95% confidence interval: -4.0 to -0.29, P < 0.01). Sensitivity analysis confirmed the robustness of the results, with no significant influence from individual studies. Additionally, publication bias was not detected, supporting the reliability and generalizability of the findings. These results underscore the efficacy of tDCS as a therapeutic intervention for auditory hallucinations in schizophrenia. tDCS significantly reduces auditory hallucinations in schizophrenia, suggesting its potential as an effective adjunctive treatment for managing this disabling symptom. The findings highlight the practical significance of tDCS in clinical settings, particularly for patients with treatment-resistant auditory hallucinations.

Auditory verbal hallucinations in schizophrenia may be due to dysfunctional inner speech-related cortical areas. Repetitive transcranial magnetic stimulation (rTMS) has been reported to be an effective treatment of hallucinations. In a cross-over sham controlled study, we guided rTMS stereotactically to inner speech-related cortical areas in hallucinating patients. These areas were identified individually prior to rTMS using fMRI in a subgroup of our patients. Active stimulation was applied over Broca's area and over the superior temporal gyrus as determined by fMRI, or according to structural images in the remaining patients. rTMS did not lead to a significant reduction of hallucination severity. Conclusively, rTMS has to be regarded critically as a possible novel tool for the treatment of hallucinations.