Treatment Of Auditory Verbal Hallucinations Research Articles

Comparative study about the therapeutic effect of cTBS and rTMS in the treatment of auditory verbal hallucinations in schizophrenia.

This study aims to compare the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) and continuous theta-burst stimulation (cTBS) treatment in schizophrenia patients with auditory verbal hallucinations (AVHs). We enrolled 64 schizophrenia patients with AVHs who were treated with either rTMS (n = 32) or cTBS (n = 32), and we compared the clinical outcomes by evaluating parameters from motor evoked potentials, Positive and Negative Syndrome Scale (PANSS), Auditory Hallucination Rating Scale (AHRS), and MATRICS Consensus Cognitive Battery (MCCB), as well as the changes of serum neurotrophic factors before and after the treatment. After the treatment, both treatments resulted in reduced PANSS scores, with the cTBS group showing more substantial symptom improvement across positive, negative, and general symptoms, highlighting the enhanced efficacy of cTBS. Cognitive functions assessed by MCCB also improved in both groups, with cTBS showing a generally higher therapeutic effect. Serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) increased following treatment in both groups, with a more notable increase after cTBS, while GABA and glutamate levels remained unchanged. Cardiovascular indices were unaffected by either treatment, suggesting no significant impact on cardiovascular health. Our study found that both rTMS and cTBS treatment can exhibit therapeutic effects in the management of AVHs in patients with schizophrenia. However, cTBS treatment generally shows a higher therapeutic effect than rTMS treatment.

Status and Clinical Experiences from the Challenge Trial – A Randomized Controlled Trial Investigating Virtual Reality-based Therapy for Auditory Hallucinations

Background: Auditory verbal hallucinations are a prevalent symptom in schizophrenia and other psychotic disorders, affecting around 70% of patients. A sizable proportion does not achieve adequate treatment response with current interventions, including antipsychotic medication. Virtual reality-based therapy (VRT) shows promise as a new intervention. Methods: The Challenge Trial is a randomized controlled study examining the efficacy of VRT compared to standard treatment for auditory hallucinations in patients with psychotic disorders. In the intervention arm, virtual reality software and voice modulation are used to design a visual representation of the patient's voice (an avatar) and to transform the therapist's voice to sound like the voice the patient hears. The aim is to foster a dialogue for the patient to strengthen their power, practice self-efficacy, and alter their relation to the voice. During therapy, the avatar becomes more compassionate and/or less powerful. Results: Quantitative data are currently unavailable as recruitment is ongoing. Instead, the design and intervention are presented along with recruitment data, retention rates, and case vignettes. Early clinical experiences are promising, with high acceptability and tolerance among patients. The trial has successfully enrolled a diverse patient population, including those with long-standing histories of hospitalization, medication use, and chronic hallucinations. The effectiveness of VRT varies, for example, some patients have reported significant reductions in the frequency of voices and associated distress, whereas others have primarily noted improvements in emotional responses to the voices. Conclusions: Based on the first 2 years of the Challenge Trial, VRT shows considerable promise as a potential treatment for auditory verbal hallucinations.

Pilot-RCT Finds No Evidence for Modulation of Neuronal Networks of Auditory Hallucinations by Transcranial Direct Current Stimulation.

Background: Transcranial direct current stimulation (tDCS) is used as treatment for auditory verbal hallucinations (AVH). The theory behind the treatment is that tDCS increases activity in prefrontal cognitive control areas, which are assumed to be hypoactive, and simultaneously decreases activity in temporal speech perception areas, which are assumed to be hyperactive during AVH. We tested this hypofrontal/hypertemporal reversal theory by investigating anatomical, neurotransmitter, brain activity, and network connectivity changes over the course of tDCS treatment. Methods: A double-blind, randomized controlled trial was conducted with 21 patients receiving either sham or real tDCS treatment (2 mA) twice daily for 5 days. The anode was placed over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the left temporo-parietal cortex (TPC). Multimodal neuroimaging as well as clinical and neurocognitive functioning assessment were performed before, immediately after, and three months after treatment. Results: We found a small reduction in AVH severity in the real tDCS group, but no corresponding neuroimaging changes in either DLPFCD or TPC. Limitations: The study has a small sample size. Conclusion: The results suggest that the currently leading theory behind tDCS treatment of AVH may need to be revised, if confirmed by studies with larger N. Tentative findings point to the involvement of Broca’s area as a critical structure for tDCS treatment.

The application of virtual reality in the treatment of mental disorders

Virtual reality (VR) enables immersion in an interactive digital world with realistic experiences, that can be applied for controlled and personalized interventions. This review summarizes the current research on VR in the treatment of mental disorders. Selective literature search in PubMed and Google Scholar. An increasing number of publications report the therapeutic application of VR for the treatment of mental disorders. Most VR applications are based on established therapy approaches, such as exposure therapy. According to meta-analytic data, virtual exposure therapy (VRET) for specific phobia and agoraphobia with panic disorder is as effective as traditional in vivo exposure therapy. VRET for the treatment of social phobia is significantly more effective than waitlist and placebo control groups with, however, currently inconsistent metanalytic results when compared to in vivo exposure therapy. VRET for the treatment of posttraumatic stress disorder (PTSD) is similar in effectiveness compared to active psychotherapy. For psychosis, positive results have been reported for the VR-based treatment of auditory verbal hallucinations. For patients with asubstance use disorder, VR can induce craving, with still unverified diagnostic and therapeutic relevance. VRET can broaden the psychotherapy options for anxiety disorders. Encouraging results of VR-based treatments for psychosis and PTSD indicate the need for further research concerning its effectiveness and safety. In the field of substance use disorders, evaluation of clinical-orientated VR applications is needed.

Frontotemporal Transcranial Direct Current Stimulation Decreases Serum Mature Brain-Derived Neurotrophic Factor in Schizophrenia.

Although transcranial direct current stimulation (tDCS) shows promise as a treatment for auditory verbal hallucinations in patients with schizophrenia, mechanisms through which tDCS may induce beneficial effects remain unclear. Evidence points to the involvement of neuronal plasticity mechanisms that are underpinned, amongst others, by brain-derived neurotrophic factor (BDNF) in its two main forms: pro and mature peptides. Here, we aimed to investigate whether tDCS modulates neural plasticity by measuring the acute effects of tDCS on peripheral mature BDNF levels in patients with schizophrenia. Blood samples were collected in 24 patients with schizophrenia before and after they received a single session of either active (20 min, 2 mA, n = 13) or sham (n = 11) frontotemporal tDCS with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. We compared the tDCS-induced changes in serum mature BDNF (mBDNF) levels adjusted for baseline values between the two groups. The results showed that active tDCS was associated with a significantly larger decrease in mBDNF levels (mean −20% ± standard deviation 14) than sham tDCS (−8% ± 21) (F = 5.387; p = 0.030; η2 = 0.205). Thus, mature BDNF may be involved in the beneficial effects of frontotemporal tDCS observed in patients with schizophrenia.

M187. A MULTIMODAL, NEUROIMAGING STUDY OF TDCS MECHANISMS RELATED TO AUDITORY VERBAL HALLUCINATIONS IN HEALTHY INDIVIDUALS

BackgroundTranscranial direct current stimulation (tDCS) is a brain stimulation method which is growing in popularity in both research and clinical settings, especially as a treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia. However, the underlying neural mechanisms of this tDCS treatment are poorly understood. Current AVH models propose that AVH arise from hyperactivation in the left temporo parietal (LTPC), causing AVH, and from hypoactivation in the left dorsolateral prefrontal cortex (LDLPFC), leading to diminished control over AVH. We aimed to “mimic” this hyper-/hypoactivation pattern in healthy individuals with tDCS by placing the excitatory anode above the LTPC and the inhibitory cathode over the LDLPFC and then to study the effects of tDCS on these brain areas. Previous studies examined either brain activation, neurochemistry, or behavior, with other electrode montages, but few looked at those aspects together. The present study therefore examined tDCS effects with fMRI (functional magnetic resonance imaging), MR spectroscopy, behavioral tasks and simulation of the electric field in a multimodal approach. We hypothesized that tDCS would (a) lead to similar behavioral deficits in healthy individuals as in schizophrenia patients and (b) induce changes in the stimulated areas on neurotransmitter and functional activation level.MethodsThirty-two healthy participants (18 males, mean age=26 yrs) were tested twice, ca. one week apart, with either real or sham (control) 2mA tDCS for 20 min while in a GE 750, 3T MRI scanner. The order of real/sham stimulation was counterbalanced in a double-blind design. During fMRI, participants completed a dichotic listening task in a block design, in order to measure behavior and brain activation changes. Before and after fMRI/tDCS, MR spectroscopy was carried out in two voxels placed under the electrodes. The data was analyzed with repeated measures ANOVAs. After data-collection, the structural T1 sequence was used to simulate the electric field of tDCS stimulation.ResultsGlx (Glutamate and glutamine combined) showed a trend (F(1,31)=3.35, p=.077, η2p=.098) to increase after tDCS stimulation compared to before, however this was not electrode specific. Neither fMRI, nor the dichotic listening task (all F≤1.64, p≥.203, η2p≤.052) showed any stimulation specific differences between real and sham stimulation. The tDCS simulation revealed large individual differences in the electric field induced.DiscussionIn the present study, tDCS seemed to have little effect on the measured brain parameters and little validation for the AVH model was found. The mechanisms of tDCS and how it affects the underlying brain tissue are poorly understood and seem to be affected by different stimulation parameters like stimulation duration, current strength and electrode montage. To use tDCS most effectively in schizophrenia research and treatment of auditory hallucinations, it should be validated with a multitude of methods, similar to the approach described here.

Treatment of auditory verbal hallucinations with atypical antipsychotics in healthy individuals: an artificially controlled post-treatment report

ObjectiveThis study was performed to investigate the effects and associated global functional connectivity density (gFCD) alterations associated with the use of atypical antipsychotics in healthy individuals with auditory verbal hallucinations (Hi-AVHs) using gFCD mapping techniques.MethodsA magnetic resonance imaging database of 38 Hi-AVHs with chronic or severe AVH symptoms was generated. The Hi-AVHs were administered an atypical antipsychotic (risperidone) for 24 weeks and monitored for a treatment response. All patients underwent functional magnetic resonance imaging pre- and post-treatment.ResultsgFCD alterations were found in the auditory-memory-language and visual circuit regions pre- and post-treatment. However, gFCD alterations differed between patients with strong and weak treatment responses.ConclusionThis is the first report to show that atypical antipsychotics can improve the symptoms of AVHs and that the treatment effects are associated with gFCD alterations in the auditory-memory-language circuit. These findings provide a foundation for future exploration of new treatment strategies for Hi-AVHs.

Auditory verbal hallucinations in schizophrenia: current perspectives in brain stimulation treatments.

PurposeThis review reports the current perspectives of brain stimulation techniques in the treatment of auditory verbal hallucinations (AVH) in schizophrenia.MethodsA systematic search of the literature in the PubMed database revealed that the most studied techniques are noninvasive techniques (NIBS), including electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS).ResultsThe results showed that ECT could have great clinical efficacy but is currently underused in practice perhaps due to the costs associated with its limited implementation and potential associated risks. tDCS is still poorly studied and does not demonstrate sufficiently homogeneous or conclusive results yet to prove its efficacy in the treatment of AVH. However, its safe and simple implementation allows us to recommend it to patients who are refractory to other stimulation techniques. Finally, rTMS seems to be the most efficacious NIBS to offer patients with persistent AVH as an add-on therapeutic strategy. Its implementation has a non negligible cost but can be performed by a single practitioner. Great evolution in these techniques with technological progress, robotics and computer science are currently being tested and will undoubtedly improve the clinical efficacy of these procedures, particularly towards more personalized treatments such as individual rTMS targets and intensities. There are also new techniques for deep brain stimulation based on focused ultrasound that could provide much insight into the treatment of AVH in schizophrenia.ConclusionThis review suggests that add-on brain stimulation treatments could play a key role among the therapeutic strategies for auditory hallucinations reduction in schizophrenia.

No Effects of Anodal tDCS on Local GABA and Glx Levels in the Left Posterior Superior Temporal Gyrus.

A number of studies investigating the biological effects of transcranial direct current stimulation (tDCS) using magnetic resonance spectroscopy (MRS) have found that it may affect local levels of γ-aminobutyric acid (GABA), glutamate and glutamine (commonly measured together as “Glx” in spectroscopy), and N-acetyl aspartate (NAA), however, these effects depend largely on the stimulation parameters used and the cortical area targeted. Given that different cortical areas may respond to stimulation in different ways, the purpose of this experiment was to assess the as yet unexplored biological effects of tDCS in the posterior superior temporal gyrus (pSTG), an area that has attracted some attention as a potential target for the treatment of auditory verbal hallucinations in schizophrenia patients. Biochemical changes were monitored using continuous, online MRS at a field strength of 3 Tesla. Performing intrascanner stimulation, with continuous spectroscopy before, during and after stimulation, permitted the assessment of acute effects of tDCS that would otherwise be lost when simply comparing pre- and post-stimulation differences. Twenty healthy participants underwent a repeated-measures experiment in which they received both active anodal and sham intrascanner stimulation in a stratified, randomized, double-blind experiment. No significant changes in GABA, Glx, or NAA levels were observed as a result of anodal stimulation, or between active and sham stimulation, suggesting that a single session of anodal tDCS to the pSTG may be less effective than in other cortical areas that have been similarly investigated.

Toward personalized treatment of hallucinations.

Hallucinations are common and often stressful experiences, occurring in all sensory modalities. They frequently complicate many disorders or situations, such as Parkinson's disease, schizophrenia, hearing or vision loss, intoxications and delirium. Although psychoeducation, coping techniques and psychotherapy may be broadly applicable, they do not address a specific underlying brain mechanism. Pharmacotherapy may effectively alleviate hallucinations if the corresponding mechanism is present, whereas in its absence, may only cause harmful side effects. Therefore, pharmacotherapy needs input about underlying brain mechanisms. Recent findings suggest new underlying neurobiological mechanisms as possible therapeutic targets in selected patients, for example increased glutamate levels. In addition, neuronavigation can guide repetitive transcranial magnetic stimulation treatment of auditory verbal hallucinations to target-specific cortical regions. We propose the use of neuroimaging methods to better understand the interaction of different mechanisms underlying hallucinations and to use this knowledge to guide pharmacotherapy or focal brain stimulation in a personalized manner. In addition, we suggest evidence from various imaging modalities should converge to answer a research question. We believe this 'convergence of evidence' avoids the problem of overreliance on single and isolated findings.

Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial.

ClinicalTrials.gov identifier: NCT02670291.

Understanding AVATAR therapy: who, or what, is changing?

Understanding AVATAR therapy: who, or what, is changing?

Human-Avatar Symbiosis for the Treatment of Auditory Verbal Hallucinations in Schizophrenia through Virtual/Augmented Reality and Brain-Computer Interfaces.

This perspective paper faces the future of alternative treatments that take advantage of a social and cognitive approach with regards to pharmacological therapy of auditory verbal hallucinations (AVH) in patients with schizophrenia. AVH are the perception of voices in the absence of auditory stimulation and represents a severe mental health symptom. Virtual/augmented reality (VR/AR) and brain computer interfaces (BCI) are technologies that are growing more and more in different medical and psychological applications. Our position is that their combined use in computer-based therapies offers still unforeseen possibilities for the treatment of physical and mental disabilities. This is why, the paper expects that researchers and clinicians undergo a pathway toward human-avatar symbiosis for AVH by taking full advantage of new technologies. This outlook supposes to address challenging issues in the understanding of non-pharmacological treatment of schizophrenia-related disorders and the exploitation of VR/AR and BCI to achieve a real human-avatar symbiosis.

High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia.

Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

Negative Beliefs about Voices in Patients with Borderline Personality Disorder Are Associated with Distress: A Plea for Cognitive-Behavioural Therapy?

Background: Auditory verbal hallucinations (AVH) are experienced by 21-54% of patients diagnosed with a borderline personality disorder (BPD), and ensuing distress is often high. Little is known about the beliefs these patients foster about their voices, and the influence thereof on distress and need for hospitalisation. Methods: In a convenience sample of 38 BPD outpatients with AVH, data were collected with the aid of the Psychotic Symptom Rating Scales (PSYRATS), Beliefs about Voices Questionnaire (BAVQ), Social Comparison Rating Scale (SCRS), and Voice Power Differential Scale (VPDS). Results: The majority of patients with BPD who experience AVH rate their voices as malevolent and omnipotent, and higher in social rank than themselves. Moreover, their resistance against them tends to be high. These parameters correlate positively and significantly with high levels of distress experienced in relation to these AVH. The need for hospitalisation, in turn, is associated with high scores for omnipotence of the voices and distress due to AVH. However, these findings could not be confirmed in regression analyses. Conclusions: As negative beliefs can be altered with cognitive-behavioural therapy (CBT), we expect CBT to be beneficial in the treatment of AVH in BPD patients, whether or not in combination with antipsychotic medication.

Effects of low frequency rTMS treatment on brain networks for inner speech in patients with schizophrenia and auditory verbal hallucinations

IntroductionEfficacy of repetitive Transcranial Magnetic Stimulation (rTMS) targeting the temporo-parietal junction (TPJ) for the treatment of auditory verbal hallucinations (AVH) remains under debate. We assessed the influence of a 1Hz rTMS treatment on neural networks involved in a cognitive mechanism proposed to subserve AVH. MethodsPatients with schizophrenia (N=24) experiencing medication-resistant AVH completed a 10-day 1Hz rTMS treatment. Participants were randomized to active stimulation of the left or bilateral TPJ, or sham stimulation. The effects of rTMS on neural networks were investigated with an inner speech task during fMRI. Changes within and between neural networks were analyzed using Independent Component Analysis. ResultsrTMS of the left and bilateral TPJ areas resulted in a weaker network contribution of the left supramarginal gyrus to the bilateral fronto-temporal network. Left-sided rTMS resulted in stronger network contributions of the right superior temporal gyrus to the auditory-sensorimotor network, right inferior gyrus to the left fronto-parietal network, and left middle frontal gyrus to the default mode network. Bilateral rTMS was associated with a predominant inhibitory effect on network contribution. Sham stimulation showed different patterns of change compared to active rTMS. ConclusionrTMS of the left temporo-parietal region decreased the contribution of the left supramarginal gyrus to the bilateral fronto-temporal network, which may reduce the likelihood of speech intrusions. On the other hand, left rTMS appeared to increase the contribution of functionally connected regions involved in perception, cognitive control and self-referential processing. These findings hint to potential neural mechanisms underlying rTMS for hallucinations but need corroboration in larger samples.

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

Repetitive transcranial magnetic stimulation (rTMS) shows a high inter-subjects variability in the efficacy of treatment of auditory verbal hallucinations (AVH) in schizophrenia. The aim of this presentation is to demonstrate the involvement of several factors in the efficacy of rTMS such as the frequency of stimulation, the placebo effect and the brain morphology underlying the target of stimulation.MethodsA meta-analysis was conducted to determine the effect sizes of placebo effect in 21 controlled studies on rTMS in the treatment of AVH in schizophrenia. MRI was also acquired in patients treated by rTMS to evaluate the scalp to cortex distances (SDCs) and the gray matter densities (GMDs) at the target of stimulation. Finally, we evaluated the efficacy of high (20 Hz) frequency stimulation in a controlled placebo study.ResultsWeak or no placebo effect in the control groups led to reveal a superiority of active rTMS over sham rTMS in the treatment of AVH. Clinical efficacy of rTMS was also correlated with the SCD or the GMD at the region of the target stimulation. Finally, we also demonstrated that more responders were observed after 2 weeks in the active group treated by 20 Hz than in the placebo group.ConclusionWe clearly demonstrated that several factors such as high frequency, the placebo effect, anatomical cortical variations can impact on the efficacy of rTMS. These results fundamentally inform the design and the method of further controlled studies, particularly with respect to studies of rTMS in the treatment of AVH.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Non-invasive Brain Stimulation and Auditory Verbal Hallucinations: New Techniques and Future Directions.

Auditory verbal hallucinations (AVHs) are the experience of hearing a voice in the absence of any speaker. Results from recent attempts to treat AVHs with neurostimulation (rTMS or tDCS) to the left temporoparietal junction have not been conclusive, but suggest that it may be a promising treatment option for some individuals. Some evidence suggests that the therapeutic effect of neurostimulation on AVHs may result from modulation of cortical areas involved in the ability to monitor the source of self-generated information. Here, we provide a brief overview of cognitive models and neurostimulation paradigms associated with treatment of AVHs, and discuss techniques that could be explored in the future to improve the efficacy of treatment, including alternating current and random noise stimulation. Technical issues surrounding the use of neurostimulation as a treatment option are discussed (including methods to localize the targeted cortical area, and the state-dependent effects of brain stimulation), as are issues surrounding the acceptability of neurostimulation for adolescent populations and individuals who experience qualitatively different types of AVH.

Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: methods, effects and challenges.

This mini-review focuses on noninvasive brain stimulation techniques as an augmentation method for the treatment of persistent auditory verbal hallucinations (AVH) in patients with schizophrenia. Paradigmatically, we place emphasis on transcranial magnetic stimulation (TMS). We specifically discuss rationales of stimulation and consider methodological questions together with issues of phenotypic diversity in individuals with drug-refractory and persistent AVH. Eventually, we provide a brief outlook for future investigations and treatment directions. Taken together, current evidence suggests TMS as a promising method in the treatment of AVH. Low-frequency stimulation of the superior temporal cortex (STC) may reduce symptom severity and frequency. Yet clinical effects are of relatively short duration and effect sizes appear to decrease over time along with publication of larger trials. Apart from considering other innovative stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), and optimizing stimulation protocols, treatment of AVH using noninvasive brain stimulation will essentially rely on accurate identification of potential responders and non-responders for these treatment modalities. In this regard, future studies will need to consider distinct phenotypic presentations of AVH in patients with schizophrenia, together with the putative functional neurocircuitry underlying these phenotypes.

Transcranial magnetic stimulation, transcranial direct current stimulation and electroconvulsive therapy for medication-resistant psychosis of schizophrenia.

Despite adequate antipsychotic treatment, 20-30% of patients with schizophrenia fail to obtain remission from psychosis. Physical stimulation treatments may provide an alternative therapy. In this review, we summarize the most recent studies regarding repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and electroconvulsive therapy (ECT) for medication-resistant psychosis in schizophrenia. Stimulation techniques in the treatment of medication-resistant psychosis have shown inconsistent results. Initial results of rTMS for auditory verbal hallucinations (AVH) were promising, but three recent large randomized controlled trials (RCTs) show similar results of rTMS as placebo. tDCS has shown initial promise as a treatment for AVH, but only in case studies and in two small RCTs. Larger studies are needed to define its efficacy. Although psychotic symptoms generally decrease after ECT, its efficacy has not been demonstrated in comparison with placebo. Although previous meta-analyses indicate significant mean effect sizes for rTMS for intractable AVH, three recent large RCTs indicate no effect compared with placebo. The use of tDCS for resistant AVH and ECT for intractable psychosis has shown some initial promise, but adequately sized placebo-controlled RCTs are now needed. Taken together, the evidence for physical stimulation techniques to relieve medication-resistant psychosis is currently weak.