Efficacy of bilateral repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: results of a multicenter double-blind randomized controlled trial

Lange, Jozarni J. Dlabac-de; Bais, Leonie; Es, Frank D. van; Visser, Bert; Reinink, E.; Bakker, B.; Heuvel, Edwin R. van den; Alemán, André; Knegtering, Henderikus

doi:10.1017/s0033291714002360

Cited by 82 publications

(62 citation statements)

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“…In our review, we came across a single study which had a follow-up period comparable to ours. Dlabac-Delange and colleagues (2015) found sustained improvement in SANS scores over a period of 3 months with 10 Hz, total of 30000 pulses to each hemisphere [13]. Similarly, the favourable effects of rTMS in our study also seemed to be sustained over 4 months of follow-up after the intervention.…”

Section: Discussionsupporting

confidence: 84%

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A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

et al. 2020

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a b s t r a c tBackground: Research has implicated hypofrontality in the pathogenesis of Negative symptoms of schizophrenia.These symptoms are often resistant to treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to reverse this hypofrontality. Higher frequency rTMS has shown better promise, but so far there has been very little research in this area. Objective: We aimed to evaluate the efficacy of high-frequency (20 Hz) unilateral rTMS over the left Dorso-Lateral Pre-frontal Cortex (DLPFC) in the improvement of Negative symptoms in Schizophrenia. Methods:100 patients of schizophrenia with predominantly negative symptoms, were enrolled for this randomized, sham-controlled, double-blind trial.Each participant received 20 sessions of rTMS at 20 Hz frequency and 100% motor threshold, via either the active or the sham coil, over 4 weeks. A total of 2000 pulses were imparted in 10 trains per session. Negative symptoms were assessed with the SANS and PANSS. CDSS was used to rule out depressive symptoms. Assessments were carried out at baseline, postintervention, and 1-month, 2-months, 3-months and 4-months follow ups. Results: The improvement in the negative symptoms (Anhedonia, Alogia, Avolition, Attention impairment) in active group was statistically significant at 0.01 and 0.05 (p-value) as compared to sham group. Conclusions: These results suggest that high-frequency rTMS may lead to improvement in negative symptoms of schizophrenia. It may be worth considering its use as an adjunct to pharmacological treatment of negative symptoms.

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Section: Discussionsupporting

confidence: 84%

“…An important advantage in our study was the use of sham coil. Majority of the studies use the intervention coil as sham by tilting it to 90 [12,13,31]. This method has been found to induce at least some voltage in the brain [34],whereas, a sham coil is devoid of this effect.…”

Section: Discussionmentioning

confidence: 99%

A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

et al. 2020

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“…Studies with a double-blind design that had cognitive measures as secondary outcomes could principally not overserve a beneficial effect of active stimulation compared to sham stimulation. 9,22,26,27,30,34,36,41,45 Other studies 33,35,37,50 indicate a potential benefit of active neurostimulation applied to the DLPFC on verbal memory, source monitoring, cognitive flexibility, or verbal fluency, whereas the aforementioned negative studies failed to show a benefit in the same or related domains. Interestingly, one study using high-frequency rTMS applied to the left DLPFC focused on the safety effect of frontal neurostimulation and did not reveal any potential harmful effect on cognition.…”

Section: Results Of Individual Studies (Outcomes)mentioning

confidence: 99%

Repetitive Noninvasive Brain Stimulation to Modulate Cognitive Functions in Schizophrenia: A Systematic Review of Primary and Secondary Outcomes

Hasan

Strube

Palm

et al. 2016

SCHBUL

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Despite many years of research, there is still an urgent need for new therapeutic options for the treatment of cognitive deficits in schizophrenia. Noninvasive brain stimulation (NIBS) has been proposed to be such a novel add-on treatment option. The main objective of this review was to systematically evaluate the cognitive effects of repetitive NIBS in schizophrenia. As most studies have not been specifically designed to investigate cognition as primary outcome, we have focused on both, primary and secondary outcomes. The PubMed/MEDLINE database (1985-2015) was systematically searched for interventional studies investigating the effects of repetitive NIBS on schizophrenia symptoms. All interventional clinical trials using repetitive transcranial stimulation, transcranial theta burst stimulation, and transcranial direct current stimulation for the treatment of schizophrenia were extracted and analyzed with regard to cognitive measures as primary or secondary outcomes. Seventy-six full-text articles were assessed for eligibility of which 33 studies were included in the qualitative synthesis. Of these 33 studies, only 4 studies included cognition as primary outcome, whereas 29 studies included cognitive measures as secondary outcomes. A beneficial effect of frontal NIBS could not be clearly established. No evidence for a cognitive disruptive effect of NIBS (temporal lobe) in schizophrenia could be detected. Finally, a large heterogeneity between studies in terms of inclusion criteria, stimulation parameters, applied cognitive measures, and follow-up intervals was observed. This review provides the first systematic overview regarding cognitive effects of repetitive NIBS in schizophrenia.

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“…The benefits persisted up to 24 weeks [47]. A smaller (n=32) recent study utilizing bilateral TMS also found improvement in SANS scores that lasted up to three months [48]. To date, four meta-analyses have been performed regarding the effect of TMS on negative symptoms and have consistently found a moderate effect size.…”

Section: Transcranial Magnetic Stimulationmentioning

confidence: 99%

Neuromodulation Treatments for Schizophrenia

Dokucu

2015

Curr Treat Options Psych

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Opinion Statement Schizophrenia is a psychiatric disorder that causes great suffering and debilitation worldwide. We have a multitude of medications that are effective for psychosis. However, these have not been successful in treating the negative and cognitive symptom domains of schizophrenia. These symptoms are responsible for the larger part of functional impairments that result from schizophrenia. In addition, there are many patients for whom no significant improvement is achieved even in the positive symptom domain. Hence, other treatment modalities have been explored to help these patients. Electroconvulsive therapy and transcranial magnetic stimulation are two of the most promising adjunct treatment methods for medication resistant schizophrenia. Electroconvulsive therapy is the gold standard treatment for catatonias whether associated with schizophrenia, mood disorders or other non-psychiatric disorders. Although not effective for negative symptoms, electroconvulsive therapy provides substantial augmentation to antipsychotic medications in improving positive symptoms and overall severity. Electroconvulsive therapy should be considered more often in patients with inadequate response to antipsychotic medications even when they do not have prominent affective symptoms. Transcranial magnetic stimulation has emerged as a promising useful therapeutic tool in targeting medication resistant auditory hallucinations and negative symptoms. Transcranial magnetic stimulation has proven to be very safe and well-tolerated by the patients in spite of its labor intensiveness. The incorporation of transcranial magnetic stimulation to routine clinical use awaits further studies to substantiate its efficacy and to optimize and customize treatment parameters to individual patients and their symptom patterns. Moreover, combining transcranial magnetic stimulation with electroconvulsive therapy to synergize their likely different mechanisms of action is another exciting possibility.

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Efficacy of bilateral repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: results of a multicenter double-blind randomized controlled trial

Abstract: Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.

Cited by 82 publications

References 73 publications

A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

Repetitive Noninvasive Brain Stimulation to Modulate Cognitive Functions in Schizophrenia: A Systematic Review of Primary and Secondary Outcomes

Neuromodulation Treatments for Schizophrenia

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