Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation: A Randomized Clinical Trial

Abstract

Importance: Psychomotor slowing is a frequent symptom of psychosis, impairing gross and fine motor behavior. It is associated with poor outcomes and functioning, and no treatment is available.

Objective: To investigate whether 15 sessions of inhibitory repetitive transcranial magnetic stimulation (rTMS) may reduce psychomotor slowing.

Design, setting, and participants: This was a 4-arm, double-blind, randomized, sham-controlled trial at a university hospital in Switzerland. Enrollment took place from March 2019 to August 2022. Adults aged 18 to 60 years with schizophrenia spectrum disorders and severe psychomotor slowing were eligible. All patients continued existing medications, including antipsychotics and benzodiazepines. Those with substance misuse (other than nicotine), conditions associated with impaired or aberrant movement, convulsions, history of hearing problems, other conditions typically excluded from magnetic resonance imaging or TMS, any TMS treatment in the past 3 months, or those who were pregnant or breastfeeding were excluded. Of 615 patients screened for eligibility, 103 were randomized and 88 received at least 1 session of rTMS: 22 were assigned to 1-Hz rTMS, 22 to iTBS, 22 to sham, and 22 to the waiting group. Follow-up was conducted at 6 weeks and 24 weeks following the week 3 assessments including clinical, functional, and motor measures.

Interventions: Fifteen sessions of rTMS in 3 weeks over the supplementary motor area: 1-Hz rTMS, iTBS, sham, or no treatment (waiting). After 3 weeks, the waiting group received 15 sessions of 1-Hz rTMS over the supplementary motor area.

Main outcomes and measures: The main outcome was the proportion of responders at week 3 in the Salpêtrière Retardation Rating Scale (SRRS) defined as a 30% or greater reduction from baseline (last-observation-carried-forward). The SRRS has 15 items and a maximum total score of 60.

Results: Of the 88 participants analyzed, 45 were men and 43 were women. The mean (SD) age was 36.3 (12.4) years and the mean (SD) SRRS score was 24.0 (5.9). A total of 69 participants completed the study. At week 3, response rates differed between groups: 15 of 22 (68%) in the 1-Hz rTMS group, 8 of 22 (36%) in the iTBS group, 7 of 22 (32%) in the sham group, and 4 of 22 (18%) in the waiting group (χ23 = 12.1; P = .007). The 1-Hz rTMS group had more responders than sham (odds ratio [OR], 0.13; 95% CI, 0.02-0.65; P = .03), iTBS (OR, 0.12; 95% CI, 0.02-0.61; P = .02), and waiting (OR, 0.04; 95% CI, 0.01-0.22; P = .003). In the waiting group, 10 of 16 participants (63%) responded after receiving 15 sessions of 1-Hz rTMS. No serious adverse events occurred.

Conclusions and relevance: In this study, inhibitory add-on rTMS safely alleviated psychomotor slowing in psychosis compared with iTBS, sham, and no treatment. The treatment was also effective with delayed onset. Future studies need to explore the neural changes associated with supplementary motor area rTMS in psychosis.

Trial registration: ClinicalTrials.gov Identifier: NCT03921450.

Figure 1.. CONSORT Flow Diagram

Numbers for dropout reasons were summarized within groups to ensure data privacy. iTBS indicates intermittent theta burst stimulation; rTMS, repetitive transcranial magnetic stimulation. ^aIn the TMS groups, last observation carried forward analyses were conducted for all participants with at least 1 stimulation. In the waiting group, we did last observation carried forward analyses in all participants with baseline data. Thus, 22 were analyzed in this group.

Figure 2.. Responder Rates and Course of Psychomotor Slowing

Treatment arm covariates (B and D) included age and medication (baseline antipsychotics, baseline benzodiazepines, and mean dosages of antipsychotics and benzodiazepines), using last observation carried forward for missing values. The waiting sample consisted of 16 patients completing the repetitive transcranial magnetic stimulation (rTMS) treatment phase after the 3-week waiting period (C). Error bars represent SEMs. iTBS indicates intermittent theta burst stimulation. ^aSignificant at P < .05. ^bFollow-up 1 took place 6 weeks after end of treatment; follow-up 2, 24 weeks after end of treatment.