Overcoming Psychomotor Slowing in Psychosis (OCoPS-P)
Condition: Schizophrenia and Related Disorders; Schizophrenia; Schizoaffective Disorder; Brief Psychotic Disorder
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Study type: Interventional

Summary: 
      Psychomotor slowing is a major problem in psychosis. Aberrant function of the cerebral motor
      system is linked to psychomotor slowing in patients, particularly resting state hyperactivity
      in premotor cortices. A previous clinical trial indicated that inhibitory stimulation of the
      premotor cortex would reduce psychomotor slowing. The current study is further exploring this
      effect in a randomized, placebo-controlled, double-blind design with three arms of
      transcranial magnetic stimulation and measures of brain imaging and physiology prior to and
      after the intervention.
    

Detailed description: 
      As psychomotor slowing is a major problem in schizophrenia, contributing to poor functional
      outcome, and as no current treatment is effectively targeting psychomotor slowing, this study
      seeks to test noninvasive brain stimulation to overcome psychomotor slowing. Previous studies
      documented an aberrant increase of neural activity within the supplementary motor area (SMA)
      in patients with schizophrenia who had psychomotor slowing. Furthermore, a pilot study in
      major depression and schizophrenia indicated that inhibitory 1 Hz repetitive transcranial
      magnetic stimulation (rTMS) would improve psychomotor slowing in 82% of the participants.
      While this is encouraging, further evidence is needed to 1) replicate the clinical effect of
      1 Hz rTMS on the SMA in schizophrenia, 2) to test against sham stimulation, facilitatory
      stimulation and no intervention, and 3) to test the effects of rTMS on the neural circuitry.
      Therefore, OCoPS includes more patients, more treatment arms, and more outcome variables than
      the first pilot trial.

      Here we will enroll 88 patients with schizophrenia spectrum disorders and severe psychomotor
      slowing according to a standard rating scale. Subjects will be randomized to four arms, three
      of which are double blinded.

      three weeks of daily rTMS over the SMA will be delivered. The first group receives inhibitory
      1 Hz rTMS, the second group receives facilitatory intermittent theta burst stimulation
      (iTBS), and the third group receives sham stimulation with a placebo-coil. The fourth group
      will have no rTMS during the first three weeks, but will repeat the baseline measures after
      three weeks and then enter a treatment with 1Hz rTMS for three weeks. Outcome measures
      include the Salpetriere Retardation Rating Scale, observer ratings of motor behavior as well
      as measures of functioning. After the interventions, follow-up visits are planned at week 6
      and week 24.

      Finally, at baseline and after the rTMS course, patients will undergo MRI scanning for
      structural and functional alterations of the cerebral motor system.
    

Intervention name(s): 1 Hz rTMS; iTBS; Placebo
Intervention type(s): Device; Device; Drug
Intervention description(s): 1 Hz stimulation at 110% of resting motor threshold over supplementary motor area; 50 Hz theta burst stimulation at 80% of resting motor threshold over supplementary motor area; 1 Hz stimulation with the placebo TMS coil without any magnetic emission
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 3 week intervention with 15 sessions of add-on rTMS in 4 parallel arms, randomized, double-blind, placebo-controlled
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: motor behavior; psychomotor slowing; psychosis