2026 ECNP Congress

EP02-2027

Non-invasive brain stimulation to reduce negative symptoms in schizophrenia: a systematic review and network meta-analysis

Stella Schulte-Frohlinde — Y. Wei, F. Liczbinski, S. Siafis, J. Schneider-Thoma, K. Huber, S. Shi, W. Strube, U. Vogelmann, C. Li, C. Plewnia, J. Davis, R.C. Smith, F. Padberg, S. Leucht · Section Evidence-based medicine in Psychiatry and Psychotherapy EbMPP, Clinic and Polyclinic for Psychiatry and Psychotherapy Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany

2026 ECNP Congress

Background

Negative symptoms are a core and disabling dimension of schizophrenia, severely impacting patients’ functional outcomes and quality of life. Despite advances in pharmacological treatment, these symptoms remain largely refractory to antipsychotic medication and thus, strongly contribute to long-term disability. Over recent decades, non-invasive brain stimulation (NIBS) techniques - such as repetitive transcranial magnetic stimulation (rTMS), transcranial electric stimulation (tES), electroconvulsive therapy (ECT), and magnetic seizure therapy (MST) - have been increasingly explored as potential treatments for schizophrenia. These methods exert their therapeutic effect by modulating neural excitability and network connectivity. Neuroimaging evidence suggests that dysfunction of the mesocortical pathway, particularly involving the dorsolateral prefrontal cortex (DLPFC), is associated with negative symptoms, providing a neurobiological rationale for NIBS-based interventions in patients with schizophrenia. Multiple RCTs have investigated the efficacy of NIBS techniques for negative symptoms of schizophrenia, with mixed and sometimes conflicting results. A recent network meta-analysis (Tseng et al., 2022), including 48 RCTs and 2211 participants, reported that several excitatory NIBS protocols applied over the left DLPFC were associated with improvement in negative symptoms. However, that analysis was not exclusively focused on patients with predominantly negative symptoms (PNS) and did not account for sensitivity or subgroups necessary for clinical tailoring.

Aims

We are conducting a systematic review and network meta-analysis (NMA) to evaluate the comparative efficacy and safety of different NIBS techniques specifically for patients with PNS.

Methods

This study follows PRISMA-NMA guidelines and is registered on PROSPERO (CRD420261324291). We include rater-blinded RCTs comparing NIBS with sham or active control conditions in patients meeting standardized criteria for PNS (e.g., specific PANSS/SANS threshold scores). We searched Cochrane Schizophrenia Group’s specialised register until January 13th, 2026, and contacted authors to retrieve unpublished data and clarify methodological details. Two independent researchers perform data extraction and assess risk of bias using the Cochrane RoB 2.0 tool. The primary outcome is the change in negative symptom severity (e.g. PANSS-N, BPRS-N, or SANS). Secondary outcomes include depression, positive symptoms, and quality of life. Data synthesis will be conducted through pair-wise meta-analyses, followed by network meta-analysis using a random-effects model. We assess evidence certainty using the Confidence in Network Meta-Analysis (CINeMA) approach. Treatment ranking is estimated using the surface under the cumulative ranking curve (SUCRA). Subgroup-, meta-regression-, and sensitivity-analyses will be conducted to explore potential effect modifiers (e.g., sample size, baseline severity) and assess the robustness of the primary outcome.

Results

Our systematic search identified 23,710 records. Following title, abstract, and full-text screening, 42 RCTs met the inclusion criteria. Data extraction and quantitative synthesis are currently underway. Final results will be available for presentation at the congress in October.

Conclusions

This study is expected to generate the first comprehensive network meta-analytic evidence focused strictly on the efficacy and safety of NIBS for predominantly negative symptoms, with potential implications for future guidelines and treatment strategies.

References

No references