Efficacy of high-frequency repetitive transcranial magnetic stimulation on PANSS factors in schizophrenia with predominant negative symptoms – Results from an exploratory re-analysis

Hansbauer, Maximilian; Wobrock, Thomas; Kunze, Birgit; Langguth, Berthold; Landgrebe, Michael; Eichhammer, Peter; Frank, Elmar; Cordes, Joachim; Wölwer, Wolfgang; Winterer, Georg; Gäebel, Wolfgang; Hajak, Göran; Ohmann, Christian; Verde, Pablo Emilio; Rietschel, Marcella; Ahmed, Rayaz; Honer, William G.; Malchow, Berend; Strube, Wolfgang; Schneider‐Axmann, Thomas; Falkai, Peter; Hasan, Alkomiet

doi:10.1016/j.psychres.2018.02.030

Cited by 17 publications

(13 citation statements)

References 36 publications

(89 reference statements)

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“…Our further ANOVA analysis showed a significant difference in time × group interaction on poor impulse control (p < 0.05), indicating that the 20 Hz rTMS treatment has a positive effect on the PANSS excited factors compared with sham stimulation. A recent exploratory secondary analysis of the data from "rTMS for the Treatment of Negative Symptoms in Schizophrenia" (RESIS) trial reported that real rTMS significantly improved the PANSS excited factor, which was in accordance with our results 42 . However, further analysis in our study and the previous reanalysis study did not pass the Bonferroni corrections.…”

Section: Discussionsupporting

confidence: 90%

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia

et al. 2020

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Cognitive impairment is a central aspect of schizophrenia (SCZ) that occurs at the onset of the disease and is related to poor social function and outcome in patients with SCZ. Recent literatures have revealed repetitive transcranial magnetic stimulation (rTMS) to be one of the efficient medical interventions for cognitive impairments. However, no study has been conducted to investigate the treatment effectiveness of 20 Hz rTMS with neuronavigation system administered to the left dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. In this randomized, double-blind and sham-controlled study, 56 patients were enrolled in 20 Hz rTMS (n = 28) or sham stimulation (n = 28) over left DLPFC for 8 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to measure the cognitive function at baseline and after 8 weeks of rTMS treatment. The positive and negative syndrome scales (PANSS) was performed to assess the clinical symptoms at baseline, after 2-week treatment, 4-week treatment, 6-week treatment, and 8-week treatment. Totally, 15 subjects (seven in active group and eight in sham group) dropped out during the trial and the main findings were from completed 41 patients. At 2 weeks, 4 weeks, and 6 weeks, there were no significant differences in PANSS total score and subscores between the sham and treatment groups. At 8 weeks, the 20 Hz rTMS significantly increased the immediate memory score compared with the sham. Furthermore, the improvement in the immediate memory score was correlated with the decrease in the excitement factor score of the patients with SCZ. Our results suggest that 20 Hz rTMS appears to be an effective treatment for improving the cognitive performance and reducing the clinical symptoms of patients with SCZ.

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Section: Discussionsupporting

confidence: 90%

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia

et al. 2020

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“…In the RESIS trial [53], the primary endpoint of negative symptoms did not improve with HF-rTMS of LDLPFC. Interestingly, an exploratory re-analysis showed improvement in non-specific factors including excitement and general psychopathology [13]. Furthermore, a subsequent sub-group analysis in clozapine-exposed patients revealed a surprising beneficial effect on positive symptoms, as well as general and total psychopathology but not negative symptoms [51].…”

Section: Discussionmentioning

confidence: 95%

“…Though individual studies reporting worsening of positive symptoms [12] have not identified if this effect is specific to certain positive symptoms, the earliest anecdotes indicated a specific but brief detrimental effect on delusions [44,56]. More recent trials indicate that some positive symptoms such as excitement may indeed improve with HF-rTMS of LDLPFC [13]. Importantly, out of 11 controlled trials investigating the effect of prefrontal HF-rTMS, worsening of positive symptoms have been reported in only some (e.g., [22]), as highlighted by Kennedy et al [20] and Marzouk et al [27].…”

Section: Introductionmentioning

confidence: 99%

Frontal–striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS

Limongi

Mackinley

Dempster

et al. 2020

Eur Arch Psychiatry Clin Neurosci

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Repetitive transcranial magnetic stimulation (rTMS), when applied to left dorsolateral prefrontal cortex (LDLPFC), reduces negative symptoms of schizophrenia, but has no effect on positive symptoms. In a small number of cases, it appears to worsen the severity of positive symptoms. It has been hypothesized that high-frequency rTMS of the LDLPFC might increase the dopaminergic neurotransmission by driving the activity of the left striatum in the basal ganglia (LSTR)-increasing striatal dopaminergic activity. This hypothesis relies on the assumption that either the frontal-striatal connection or the intrinsic frontal and/or striatal connections covary with the severity of positive symptoms. The current work aimed to evaluate this assumption by studying the association between positive and negative symptoms severity and the effective connectivity within the frontal and striatal network using dynamic causal modeling of resting state fMRI in a sample of 19 first episode psychosis subjects. We found that the total score of positive symptoms of schizophrenia is strongly associated with the frontostriatal circuitry. Stronger intrinsic inhibitory tone of LDLPFC and LSTR, as well as decreased bidirectional excitatory influence between the LDLPFC and the LSTR is related to the severity of positive symptoms, especially delusions. We interpret that an increase in striatal dopaminergic tone that underlies positive symptoms is likely associated with increased prefrontal inhibitory tone, strengthening the frontostriatal 'brake'. Furthermore, based on our model, we propose that lessening of positive symptoms could be achieved by means of continuous theta-burst or low-frequency (1 Hz) rTMS of the prefrontal area.

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“…Surprisingly, only three studies [28,53,78] out of 35 (0.9%) revealed significant reductions in anger state after the application of brain stimulation techniques. It is interesting to highlight that both studies mainly stimulated the prefrontal cortex (PFC), which has usually been associated with behavioural control [79].…”

Section: Self-reportsmentioning

confidence: 97%

“…There were also two studies that showed significant reductions in anger levels in two different populations, such as patients who had suffered a closed-head injury 6 months earlier [75] and Alzheimer patients [76]. Finally, other studies reported a lack of effects on treatment-resistant depressive patients with no pharmacological treatment [72], on anger-state in current-abstinent smokers [73], on patients with refractory partial epilepsy who received a dosage of antiepileptics [77], and on patients with schizophrenia [78]. Even a study with mentally retarded minors with language disorders reinforced the fact that non-invasive brain stimulation techniques produced an increase in irritability in approximately 40% of these patients [74].…”

Section: Pathological Conditionsmentioning

confidence: 99%

A Systematic Review of the Effectiveness of Non-Invasive Brain Stimulation Techniques to Reduce Violence Proneness by Interfering in Anger and Irritability

Romero‐Martínez

Bressanutti

Moya-Albiol

2020

JCM

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The field of neurocriminology has proposed several treatments (e.g., pharmacological, brain surgery, androgen-deprivation therapy, neurofeedback) to reduce violence proneness, but unfortunately, their effectiveness has been limited due to their side-effects. Therefore, it is necessary to explore alternative techniques to improve patients’ behavioural regulation with minimal undesirable effects. In this regard, non-invasive brain stimulation techniques, which are based on applying changing magnetic fields or electric currents to interfere with cortical excitability, have revealed their usefulness in alleviating the symptomatology of several mental disorders. However, to our knowledge, there are no reviews that assess whether these techniques are useful for reducing violence proneness. Therefore, we conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria using the following databases: PsycINFO, PubMed, Dialnet, Psicodoc, Web of Knowledge, and the Cochrane Library. We initially identified 3746 entries, and eventually included 56 publications. Most of the studies were unanimous in concluding that the application of these techniques over the prefrontal cortex (PFC) was not sufficient to promote anger and irritability reductions in euthymic individuals of both genders. Nevertheless, the application of non-invasive brain stimulation techniques, especially transcranial direct current stimulation, over the right PFC seemed to reduce violent reactions in these individuals by interfering with the interpretation of the unfavourable situations (e.g., threating signals) or inner states that evoked anger. In antisocial and pathological populations, the conclusions were provided by a few pilot studies with important methodological weaknesses. The main conclusion of these studies was that bilateral stimulation of the PFC satisfactorily reduced anger and irritability only in inmates, patients with autism spectrum disorders (ASD), people who suffered a closed-head injury, and agitated patients with Alzheimer’s disease. Moreover, combining these techniques with risperidone considerably reduced aggressiveness in these patients. Therefore, it is necessary to be cautious about the benefits of these techniques to control anger, due the methodological weaknesses of these studies. Nonetheless, they offer valuable opportunities to prevent violence by designing new treatments combining brain stimulation with current strategies, such as psychotherapy and psychopharmacology, in order to promote lasting changes.

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Efficacy of high-frequency repetitive transcranial magnetic stimulation on PANSS factors in schizophrenia with predominant negative symptoms – Results from an exploratory re-analysis

Cited by 17 publications

References 36 publications

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia

Frontal–striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS

A Systematic Review of the Effectiveness of Non-Invasive Brain Stimulation Techniques to Reduce Violence Proneness by Interfering in Anger and Irritability

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