Brain stimulation may have distinct near-maximal effective doses across mental disorders

Key takeaways:

• Researchers analyzed 110 studies with 4,820 participants receiving noninvasive brain stimulation.
• Significant dose-response associations were found in schizophrenia, depression, OCD, substance use disorders.

Significant dose-response associations were found for transcranial magnetic stimulation and transcranial direct current stimulation across several mental disorders, including schizophrenia and depression, according to research.

“Evidence providing support for the efficacy of noninvasive brain stimulation (NIBS) techniques, including transcranial magnetic stimulation and transcranial direct current stimulation in the treatment of mental disorders ... has accumulated steadily,” Michel Sabé, MD, from the division of adult psychiatry, department of psychiatry University Hospitals of Geneva, and colleagues wrote in JAMA Network Open. “However, despite the increased use of NIBS interventions in clinical practice, a standard dose definition currently is not available.”

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

Researchers reviewed 110 randomized clinical trials with 4,820 participants (mean age, 42.3 years; 61.4% men) that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any 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 results, significant dose-response associations were identified with bell-shaped curves for schizophrenia, with high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ²=9.35; df=2) and TMS on the left temporoparietal junction for resistant hallucinations (χ²=36.52; df=2); for depression, HF-DLPFC TMS (χ²=14.49; df=2); for treatment-resistant depression, LDLPFC tDCS (χ²=14.56; df=2); and for substance use disorder, LDLPFC tDCS (χ²=33.63; df=2).

Researchers also reported significant dose-response associations, with plateaued or ascending curves, for depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ²=25.67; df=2); for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ²=5.86; df=2); for obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ²=20.65; df=2) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ²=15.19; df=2); and for PTSD, LF-RDLPFC TMS with ascending curve (χ²=54.15; df=2).

Researchers confirmed these findings via sensitivity analyses, but acknowledged the study had several limitations, including a restricted number of participants and omission of various NIBS parameters in the included trials.

“The findings of this systematic review and dose-response meta-analysis contribute to the understanding of optimal stimulation parameters across disorders and brain areas in the field of neuromodulation,” Sabé and colleagues wrote. ‘Our analysis suggests a minimum of 150 participants is necessary to establish reliable dose-response models for each stimulation type.”