The Safety and Effectiveness of dTMS for Reducing Antipsychotic-induced Weight Gain

The Effects of Improving Antipsychotic-induced Weight Gain by Accelerated dTMS After Food Cue-induced Craving, A Double-Blind, Randomized, Sham-Controlled Clinical Trial.

Antipsychotic-induced metabolic disturbances, especially weight gain, are common in patients with schizophrenia. There are no hitherto effective treatments for reducing antipsychotic-induced weight gain. Recently, research suggest that Accelerated dTMS (a-dTMS) which deliver more than one daily TMS session indicates greater efficacy than other TMS treatment. Symptom provocation is believed to improve the clinical responses to TMS. In this study, the investigators, firstly, evaluate the safety and effectiveness of a-dTMS for reducing antipsychotic-induced weight gain and secondly, to establish a predictive model of therapeutic response and to explore the underlying mechanisms of dTMS for reducing antipsychotic-induced weight gain, based on multimodal radiomics and metabolomics approaches.

The underlying causes of antipsychotic-induced weight gain are still unknown. Some research point out that it has something to do with metabolic disturbances and changes in appetite and food intake, acting food-craving-like behave which some points are similar to addiction. With fMRI study, it is reported having dysfunction between prefrontal and insula cortex of its cognitive regulation, interoceptive signals and reward control. dTMS, H coil in particular, simultaneously targets prefrontal and insula cortex, approved by FDA for Smoking Addiction recently. Previous study has been deconstrued that H coil could significantly improve weight gain than figure-eight Coils. Moreover, It is reckoned that TMS has state-dependent effects on brain circuitry, suspected that symptom provocation may be made it more susceptible to modulation which may improve response. Therefore, this study is to explore the efficacy of a-dTMS on antipsychotic-induced appetite, and use multimodal radiomics and metabolomics approaches to unveil the underlying mechanisms of dTMS for reducing antipsychotic-induced weight gain.

With regard to investigate this, we will be carried out a randomized, double-blind, sham-controlled clinical trial. 60 Patients with schizophrenia will be randomly treated with active a-dTMS or sham condition for 3 sections' interventions per day last for 10 days. The follow-ups are at baseline, the 12th day and the 42th day after the end of treatment. The main outcome measures include the change in body weight, BMI, TFEQ score, FCQ-S score, FCQ-T score and the resting and task-state EEG-fMRI imaging data.

Inclusion Criteria:

• Aged between 18-60.
• Meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for schizophrenia, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5).
• Gaining body weight around 7% after intaking antipsychotics within 2 years.
• Participants were on a stable medication regimen at the time of enrollment. ●Written informed consent was obtained from both the participants and their legally authorized guardians.

Exclusion Criteria:

• Participants who switch antipsychotic drugs (APDs) or require a dose modification exceeding 25% of the baseline dosage during the study period.
• Diagnosed with other mental diseases in accordance with DSM-V.
• Comorbid with other severe physiological diseases.
• Active suicidal ideation.
• A history of alcohol or substance use disorder (or abuse).
• Presence of metal implants or any other conditions contraindicated for magnetic resonance imaging (MRI).
• Presence of intracranial metal or electronic devices, a personal or family history of epilepsy, or any other standard contraindications to deep transcranial magnetic stimulation.
• Receipt of regular transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), or weight-loss interventions within the past month.
• Pregnant or lactating women