Transcranial Magnetic Stimulation for "Voices"
Condition: Schizophrenia; Hallucinations
MeSH terms: Hallucinations; Schizophrenia
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will determine the efficacy of MRI-guided transcranial magnetic stimulation
      (TMS)in reducing "voices" and other symptoms experienced by people with schizophrenia and
      schizoaffective disorder. In addition, the study will determine duration of improvement
      obtained during the course of trial participation via on-going monthly contact with study
      participants for up to 1 year after the trial.
    

Detailed description: 
      Schizophrenia is a severely disabling brain disorder that affects about 1% of the United
      States population. Approximately 50 to 80% of people with schizophrenia experience "voices,"
      also known as auditory hallucinations. These hallucinations consist of spoken speech, which
      sometimes replicates the speaking voice of a familiar person, and sometimes reflects a
      speaking voice that is not known but becomes highly recognizable. The phrases and sentences
      expressed by "voices" are often highly disruptive, and may comment, cajole, criticize, and,
      in some cases, command the patient. They are often but not invariably distressing, and can
      disrupt one's ability to interact with others, work, study, and sleep. In about 25% of cases,
      medication treatment is either completely ineffective or only partially effective in
      relieving "voices." Effective treatment alternatives are needed to improve this troubling and
      often disabling symptom.

      Recent studies have suggested that auditory hallucinations arise from parts of the brain that
      are ordinarily involved in perceiving actual spoken speech. Low frequency repetitive
      transcranial magnetic stimulation (rTMS), a technique that uses an electromagnet to induce
      reductions in cortical brain activity, may therefore be effective in quieting auditory
      hallucinations. The potential usefulness of this approach has been demonstrated by previous
      studies conducted at our medical center. This new study uses magnetic resonance imaging (MRI)
      to locate two areas of the brain involved in speech perception. These areas are in Wernicke's
      area in the left superior temporal gyrus, and in the right hemisphere in an analogous site in
      the superior temporal gyrus. Repetitive TMS is specifically positioned to reduce cortical
      excitability or reactivity at these two brain regions.

      Participants in this double blind study will be randomly assigned to receive either real
      rTMS, or placebo stimulation, which feels similar to real rTMS but does not produce direct
      brain effects. Depending on group assignment, participation may last 4 to 8 weeks. Over the
      first 2 weeks, all participants will undergo two sequences of rTMS, each consisting of five
      16-minute sessions. One sequence is directed to left Wernicke's area and the other sequence
      is directed to the right-sided equivalent area. During the third week, participants will
      receive five additional sessions to the left or right site that appeared to produce greater
      clinical improvement. All participants will then be informed as to whether they received real
      or placebo stimulation. Participants who received real stimulation will be offered 5
      additional stimulation sessions at the brain site that achieved the best response.
      Participants who received placebo stimulation will be offered real stimulation for up to
      twenty sessions over 4 weeks using the same schedule described above. Assessments of severity
      of hallucinations and other clinical symptoms will be conducted after every fifth rTMS
      session by a clinician who does not know whether the participant is receiving real or placebo
      stimulation.

      Neuropsychological testing will also be done before, during, and after the trial. Our
      previous trial demonstrated some improvement in verbal processing with no significant
      impairments in terms of memory, language or cognitive function. However, insofar as this
      trial involves a greater total "dose" of rTMS, careful monitoring of these functions is
      conducted throughout the trial.

      In addition, the study will determine the degree to which improvement obtained during the
      course of trial is sustained over the ensuing months. This is accomplished via on-going
      monthly contact with study participants for up to 1 year after the last rTMS stimulation
      session.
    

Intervention name(s): 1-hertz Repetitive Transcranial Magnetic Stimulation; Active 1-Hertz Repetitive transcranial magnetic stimulation
Intervention type(s): Device; Device
Intervention description(s): Sham stimulation given to Wernicke's area or a right homologous area for 16 minutes per day x 5 days for week I, the same for week II with switch from right to left or left to right, and 5 more stimulation sessions (16 minutes per session) to the side producing greater benefit for week III.; Active stimulation given to Wernicke's area or a right homologous area for 16 minutes per day x 5 days for week I, the same for week II with switch from right to left or left to right, and 5 more stimulation sessions (16 minutes per session) to the side producing greater benefit for week III.
Other intervention name(s): Magstim Rapid-2; Magstim Rapid-2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Auditory Hallucinations; Schizophrenia; Schizoaffective Disorder; Repetitive Transcranial Magnetic Stimulation; Wernicke's Area; Superior Temporal Gyrus