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Key lessons learned:

• Researchers analyzed 110 studies involving 4,820 participants who received noninvasive brain stimulation.
• Significant dose-response associations were found in schizophrenia, depression, OCD, and substance abuse.

Research has shown that significant dose-response associations have been found for transcranial magnetic stimulation and transcranial direct current stimulation in several mental disorders, including schizophrenia and depression.

“Evidence has steadily accumulated to support the effectiveness of noninvasive brain stimulation (NIBS) techniques, including transcranial magnetic stimulation and transcranial direct current stimulation in the treatment of mental disorders,” Michael Sawshe, doctor, from the Adult Psychiatry Department, Department of Psychiatry, Geneva University Hospitals, and colleagues wrote in JAMA Network Opened“However, despite the increased use of NIBS interventions in clinical practice, no standard dose definition is currently available.”

Results of a systematic review and meta-analysis of non-invasive brain stimulation for a range of psychiatric conditions found significant dose-response associations, but no maximum effective dose was identified for each condition. Imagician: Adobe Stock

To investigate the associations between specific NIBS dose stimulation parameters and treatment response across a range of psychiatric disorders, Sabé and colleagues conducted a systematic review and meta-analysis. This was extended to April 30, 2023, to include an earlier review of studies from PubMed, OVID, and Web of Knowledge.

Researchers reviewed 110 randomized clinical trials involving 4,820 participants (mean age, 42.3 years; 61.4% men) that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for a mental disorder in adults. The primary outcome was near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS.

According to the results, significant dose-response associations were identified with bell-shaped curves for schizophrenia, with high-frequency (HF) TMS over the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (X2=9.35; df=2) and TMS on the left temporoparietal junction for resistant hallucinations (X2=36.52; df=2); for depression, HF-DLPFC TMS (X2=14.49; df=2); for treatment-resistant depression, LDLPFC tDCS (X2=14.56; df=2); and for substance use disorder, LDLPFC tDCS (X2= 33.63; df=2).

Researchers also reported significant dose-response associations, with plateau or ascending curves, for depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (X2=25.67; df=2); for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (X2=5.86; df=2); for obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (X2=20.65; df=2) and LF TMS on the orbitofrontal cortex with a plateau curve (X2=15.19; df=2); and for PTSD, LF-RDLPFC TMS with ascending curve (X2= 54.15; df=2).

Researchers confirmed these findings through sensitivity analyses, but acknowledged that the study had several limitations, including a limited number of participants and the lack of several NIBS parameters in the included studies.

“The findings of this systematic review and dose-response meta-analysis contribute to the understanding of optimal stimulation parameters for disorders and brain regions in the field of neuromodulation,” Sabé and colleagues wrote. “Our analysis suggests that at least 150 participants are needed to establish reliable dose-response models for each stimulation type.”

Sources/Disclosures