Treatment Of Hallucinations In Schizophrenia Research Articles

Cost-utility analysis of rTMS as add-on therapy to standard care for the treatment of hallucinations in schizophrenia.

AbstractBackgroundThis research evaluates the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) as add-on therapy to standard care for adults with schizophrenia from an Australian health system perspective.MethodsA Markov model estimated costs in 2021 Australian dollars and Disability-Adjusted Life-Years (DALYs) averted with rTMS added to standard care compared to standard care alone over 12-months for adults aged 25–65 years with hallucinations in schizophrenia refractory to other therapies. rTMS effect size was sourced from a meta-analysis and converted to a relative risk using the Cochrane conversion method. Probabilistic sensitivity analysis evaluated uncertainty in effect size and disability weights. One-way sensitivity analyses varied rTMS session cost and effectiveness, time horizon and inpatient costs.ResultsThe base-case average incremental cost-effectiveness ratio (ICER) was $87,310/DALY averted (95% UI: $10,157–$97,877). Reducing rTMS session cost to $100 lowered the ICER to $9,127/DALY (95% UI: Dominant–$50,699). A 4-year time horizon resulted in rTMS being less costly and more effective (Dominant) than standard care. Decreasing the 3-month probability of relapse with rTMS to 4.6% resulted in a 71% probability of rTMS being cost-effective.ConclusionsUsing a threshold of $50,000/ DALY averted, rTMS as add-on therapy to standard care for the treatment of refractory hallucinations in schizophrenia would not be considered a cost-effective treatment option compared to standard care alone. However, given the refractory nature of this condition and the relatively small size of this population, it may be reasonable for decision-makers to adopt a higher ICER threshold.

S58. A RANDOMIZED CONTROLLED TRIAL COMPARING VIRTUAL REALITY THERAPY TO COGNITIVE BEHAVIORAL THERAPY IN SCHIZOPHRENIA WITH TREATMENT REFRACTORY HALLUCINATIONS: PRELIMINARY RESULTS

BackgroundWhile many pharmacological and psychosocial interventions are available, many treatment-resistant schizophrenia patients continue to suffer from persistent psychotic symptoms, mainly auditory verbal hallucinations (AVH). Recently, a psychological therapy using computerized technology has shown large therapeutic effects on AVH severity by enabling patients to engage in a dialogue with a representation of their distressing voices. These very hopeful results have been extended by our team using immersive 3D virtual reality. The results of VR therapy (VRT) in our pilot trial involving 15 schizophrenia patients with refractory AVH were clinically promising for the severity and distress related to hallucinations, illness symptomatology, depressive symptoms and quality of life. Notably, clinical improvements of our pilot remained significant at our 3-month follow-up. Such findings suggest that VRT seems to be a highly promising intervention for refractory AVH.MethodsTo further research in this field, the primary goal of this randomized-controlled trial is to show that VRT is superior to a widely utilized psychotherapy, that is Cognitive behavioral therapy (CBT), for the treatment of persistent auditory verbal hallucinations in schizophrenia. Our secondary goal is to examine the effects of these interventions on beliefs about voices, illness symptomatology, mood symptoms (anxiety and depression), self-esteem, level of functioning and quality of life.This is a single-blinded randomized-controlled, single-site parallel study of VRT versus CBT. Each treatment group will include 52 randomized participants (assuming 20% attrition) of over 18 years of age hearing persecutory voices and suffering from treatment resistant schizophrenia or schizoaffective disorder. Diagnoses will be established with the Structured Interview for DSM-V. Patients will be included if they have been hearing persecutor voices that did not respond to ≥2 antipsychotic trials.VRT comprises of 9 weekly sessions: 1 avatar creation session and 8 therapeutic sessions, where the patients are confronted to their reproduced hallucinatory experience and are encouraged to enter in a dialogue with their virtual persecutor. CBT includes 9 weekly sessions consisting of learning modules and task assignments. Subjects will be evaluated at baseline and post-treatment to assess primary (auditory verbal hallucinations as measured with the Psychotic Symptoms Rating Scale) and secondary outcomes. Mixed Anova analyses will be performed to measure and compare the effects of both interventions.ResultsPresently, 37 patients have been recruited and 9 have abandoned the study. Our preliminary results on 28 patients show that there is no significant difference between the treatment conditions for all our measures. As expected, more participants will be required to show the superiority of VRT over CBT. However, when performing separate ANOVA analyses for each condition, VRT shows significant improvements of auditory verbal hallucinations severity after the treatment (on our primary outcome) contrarily to CBT. VRT also produced significant decreases on the beliefs that voices are omnipotent and malevolent, on psychotic symptomatology, depressive symptoms and an increase on quality of life. CBT obtained no significant improvements.DiscussionWhile limited by the small number of patients, such findings are nonetheless already supporting the hypothesis of the superiority of VRT on auditory verbal hallucinations. As expected, a moderate effect is found for our adapted short CBT for psychosis, though not significant at this point. The current trial will contribute to the validation of a novel innovative approach answering a fundamental clinical need.

M104. Efficacy of Transcranial Direct Current Stimulation (tDCS) as a Treatment for Persistent Hallucinations in Patients With Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract Hallucinations are common symptoms in schizophrenia occurring in about 60% to 80% of patients. Antipsychotics are effective in 70% to 80% of patients, while the remaining 20% to 30% of patients continue to experience persistent hallucinations despite medication. Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation technique, which has been studied as a treatment for persistent hallucinations in schizophrenia. Given the growing clinical interest in using tDCS as a treatment for persistent hallucination, we conducted a systematic review and meta-analysis of the efficacy of tDCS for alleviating hallucinations in schizophrenia. Systematic search of Medline, Embase, Cochrane Central Register of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL for relevant studies was done up to March 16, 2016. Bibliographies of retrieved articles and previous reviews were also included in the search. Eligibility criteria for study selection included randomized controlled trials that compared the efficacy of tDCS with sham stimulation for treating persistent hallucinations in patients with schizophrenia. Two reviewers independently extracted data and assessed study risk of bias. Standard mean differences across trials were pooled. Subgroup analyses were performed, and heterogeneity and potential publication bias were assessed. The GRADE system was used to evaluate the quality of evidence and confidence in the conclusions. Main outcome measure Hallucination severity evaluated by a random effects meta-analysis model. Five eligible randomized sham-controlled trials involving 121 patients were included in the meta-analysis. Most patients were reported to have persistent hallucinations despite adequate antipsychotic treatment. Active tDCS (2 mA stimulation for 20 min) was administered once or twice daily, for 5 to 15 sessions, with cathode over the left temporo-parietal junction and anode over the left dorsolateral prefrontal cortex or right supraorbital ridge. The pooled effects from all trials with an overall “moderate quality” (GRADE) was −0.15 (95% CI −0.55 to 0.25), indicating no beneficial effects of tDCS on persistent hallucination in schizophrenia. The heterogeneity between trials was low ( = 37%) and no serious adverse effects were reported. Based on current moderate-quality evidence, tDCS has no beneficial effects on persistent hallucination in schizophrenia, particularly when administered once daily. Future studies should focus on twice daily stimulations to determine if tDCS is effective for treating persistent hallucinations in schizophrenia.

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.

Treatment of refractory auditory hallucinations in schizophrenia by rTMS: Positive impact of negative double blind controlled study

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.

Transcranial Stimulation for Psychosis: The Relationship Between Effect Size and Published Findings

Back to table of contents Previous article Next article Communications and UpdatesFull AccessTranscranial Stimulation for Psychosis: The Relationship Between Effect Size and Published FindingsIris E. Sommer, M.D., Ph.D., Andre Aleman, M.D., Ph.D., Christina W. Slotema, M.D., Ph.D., and Dennis J.L.G. Schutter, Ph.D.Iris E. SommerUtrecht, NetherlandsSearch for more papers by this author, M.D., Ph.D., Andre AlemanGroningen, NetherlandsSearch for more papers by this author, M.D., Ph.D., Christina W. SlotemaThe Hague, NetherlandsSearch for more papers by this author, M.D., Ph.D., and Dennis J.L.G. SchutterUtrecht, NetherlandsSearch for more papers by this author, Ph.D.Published Online:1 Nov 2012https://doi.org/10.1176/appi.ajp.2012.12060741AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We read with interest the article by Brunelin et al. (1) in the July issue, which described the application of transcranial direct-current stimulation (tDCS) in the treatment of both auditory hallucinations and negative symptoms simultaneously. Fifteen patients received 10 tDCS treatments and another 15 patients received sham stimulation. An effect size of 1.58 was reported for refractory hallucinations, which is remarkably large when compared with the effect sizes of antipsychotic medication (0.4–0.6). The effect size for negative symptoms was also larger than 1.Clinical trials involving nonconvulsive brain stimulation in schizophrenia were first introduced in 1999. Initial effect sizes were very large while samples were small. Some years later, large negative studies were published. To date, 17 placebo-controlled transcranial magnetic stimulation (TMS) studies on hallucinations have been published. The mean weighted effect size is now around 0.3 (2). Yet, the negative correlation between effect size and year of publication suggests that over time, the mean effect size may become smaller.The trend of effect sizes for new techniques decreasing over time is by no means specific for TMS or tDCS. It is a general trend that can be observed when new treatments are introduced (3). For example, when selective serotonin reuptake inhibitors (SSRIs) were introduced for depression, effect sizes greater than 1 were reported, which created their legacy as a wonder drug. Over the course of 20 years, the mean effect size of SSRIs decreased to around 0.3. A similar trend was demonstrated for cognitive-behavioral therapy (4).This trend likely results from publication bias. A remarkably high effect size suggests the discovery of a new wonder treatment. Studies with such findings are therefore easily published in high-impact journals (5). In contrast, studies of similar sample size with marginally or nonsignificant findings are less likely to be accepted for publication. Usually, after some years, negative studies with large sample sizes become available. This is when meta-analyses start to detect a decrease in efficacy.In this view, the Brunelin et al. study (1) is exemplary of an initial placebo-controlled study applying a new technique: it included a small sample, found remarkably large effects, and is published in a high-impact journal.We sincerely hope that tDCS is the exception to the rule—as a cheap, safe, and highly effective method to treat both refractory hallucinations and negative symptoms is most welcome. However, given the previous observations for other new treatments, it is realistic to expect that 10 years from now the mean weighted effect size of tDCS will be around 0.3.Utrecht, NetherlandsGroningen, NetherlandsThe Hague, NetherlandsUtrecht, NetherlandsThe authors report no financial relationships with commercial interests.References1 Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, Saoud M, Mechri A, Poulet E: Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry 2012; 169:719–724Link, Google Scholar2 Slotema CW, Aleman A, Daskalakis ZJ, Sommer IE: Meta-analysis of repetitive transcranial magnetic stimulation in the treatment of auditory verbal hallucinations: update and effects after one month. Schizophr Res (Epub ahead of print, Sep 29, 2012)Google Scholar3 Munafò MR, Flint J: How reliable are scientific studies? Br J Psychiatry 2010; 197:257–258Crossref, Medline, Google Scholar4 Cuijpers P, Smit F, Bohlmeijer E, Hollon SD, Andersson G: Efficacy of cognitive-behavioral therapy and other psychological treatments for adult depression: meta-analytic study of publication bias. Br J Psychiatry 2010; 196:173–178Crossref, Medline, Google Scholar5 Siontis KC, Evangelou E, Ioannidis JP: Magnitude of effects in clinical trials published in high-impact general medical journals. Int J Epidemiol 2011; 40:1280–1291Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByCortical folding abnormalities in patients with schizophrenia who have persistent auditory verbal hallucinationsEuropean Neuropsychopharmacology, Vol. 28, No. 2Schizophrenia Research, Vol. 201Systematic Reviews, Vol. 5, No. 1Therapeutic Applications of rTMS for Psychiatric and Neurological Conditions5 June 2015Transcranial direct current stimulation als behandeling voor auditieve hallucinaties21 May 2015 | Neuropraxis, Vol. 19, No. 3Transcranial magnetic stimulation, transcranial direct current stimulation and electroconvulsive therapy for medication-resistant psychosis of schizophreniaCurrent Opinion in Psychiatry, Vol. 28, No. 3, Vol. 129Frontiers in Psychology, Vol. 6Molecular Neurobiology, Vol. 49, No. 1Clinical Psychopharmacology and Neuroscience, Vol. 11, No. 3 Volume 169Issue 11 November 2012Pages 1211-1211 Metrics PDF download History Accepted 1 August 2012 Published online 1 November 2012 Published in print 1 November 2012

The Treatment of Hallucinations in Schizophrenia Spectrum Disorders

This article reviews the treatment of hallucinations in schizophrenia. The first treatment option for hallucinations in schizophrenia is antipsychotic medication, which can induce a rapid decrease in severity. Only 8% of first-episode patients still experience mild to moderate hallucinations after continuing medication for 1 year. Olanzapine, amisulpride, ziprasidone, and quetiapine are equally effective against hallucinations, but haloperidol may be slightly inferior. If the drug of first choice provides inadequate improvement, it is probably best to switch medication after 2-4 weeks of treatment. Clozapine is the drug of choice for patients who are resistant to 2 antipsychotic agents. Blood levels should be above 350-450 μg/ml for maximal effect. For relapse prevention, medication should be continued in the same dose. Depot medication should be considered for all patients because nonadherence is high. Cognitive-behavioral therapy (CBT) can be applied as an augmentation to antipsychotic medication. The success of CBT depends on the reduction of catastrophic appraisals, thereby reducing the concurrent anxiety and distress. CBT aims at reducing the emotional distress associated with auditory hallucinations and develops new coping strategies. Transcranial magnetic stimulation (TMS) is capable of reducing the frequency and severity of auditory hallucinations. Several meta-analyses found significantly better symptom reduction for low-frequency repetitive TMS as compared with placebo. Consequently, TMS currently has the status of a potentially useful treatment method for auditory hallucinations, but only in combination with state of the art antipsychotic treatment. Electroconvulsive therapy (ECT) is considered a last resort for treatment-resistant psychosis. Although several studies showed clinical improvement, a specific reduction in hallucination severity has never been demonstrated.