Transcranial Magnetic Stimulation (TMS) Treatment for Patients With Persistent Auditory Hallucinations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00042159
Recruitment Status : Completed
First Posted : July 26, 2002
Last Update Posted : August 6, 2013
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Ralph Edward Hoffman, Yale University

Brief Summary:
This study will evaluate the long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with auditory hallucinations.

Condition or disease Intervention/treatment Phase
Schizophrenia Hallucinations Device: repetitive transcranial magnetic stimulation Not Applicable

Detailed Description:

Auditory hallucinations can cause distress, functional disability, and problems in controlling behavior. In addition, auditory hallucinations are often resistant to drug treatment. Brain imaging studies suggest that voices arise from parts of the brain that are ordinarily involved in perceiving spoken speech. In TMS, an electromagnet placed on the scalp produces magnetic pulses that pass through the skull and stimulate the underlying cerebral cortex (a part of the brain). Low frequency (once per second) TMS is known to reduce reactivity or excitability of the part of the brain directly stimulated without damaging brain tissue. This study will determine if low frequency rTMS directed to brain areas responsible for speech processing can be used as an alternative treatment for auditory hallucinations and other related psychotic symptoms.

Before starting rTMS, patients will undergo: (1) a medical and psychiatric evaluation, (2) neuropsychological tests to assess concentration and memory abilities, and (3) an fMRI brain scan (which takes about 1 ¼ hours and does not require any injections). After these evaluations are completed, patients will be randomly assigned (e.g., by the flip of a coin) to receive either low frequency rTMS or placebo stimulation for 16 minutes per day over a 10-day period. During this time, the patient will not know whether (s)he is receiving the real or the placebo stimulation. For 5 days, stimulation will be administered to an area of the left temporal lobe of the brain that is involved in perceiving speech. This area is called Wernicke's area. For another 5-day period, a similar area on the right side of the brain will be stimulated. After the 10-day trial is completed, the patient will be told if (s)he received real or placebo TMS. If the patient received real TMS and experienced significant improvement in "voices", (s)he can choose to receive more stimulation to that part of the brain that produced greater improvement. If the patient has received only placebo stimulation, (s)he will then be offered a trial of real rTMS.

TMS is generally not painful, but can be uncomfortable due to a tingling or knocking sensation and/or contraction of scalp and facial muscles. There is a small risk of seizure associated with TMS, but for the frequency of stimulation used in this study (1 stimulation per second), this risk is significant only for patients who have a prior history of seizures, epilepsy, or other neurological problem. We have given TMS to more than 90 persons with schizophrenia and auditory hallucinations and have not had a case of seizure. We are also concerned that TMS may cause memory or concentration problems. Therefore, we carefully monitor patients for early signs of such difficulties, using daily questionnaire assessments and weekly neuropsychological tests. If we suspect that a patient is experiencing problems with memory or concentration, the trial is stopped. A small percentage of patients in our previous studies (less than 5%) reported problems with memory that ended soon after the trial was stopped.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: TMS Intervention Development for Auditory Hallucinations
Study Start Date : July 2002
Actual Primary Completion Date : July 2003
Actual Study Completion Date : June 2004

Resource links provided by the National Library of Medicine

Intervention Details:
  • Device: repetitive transcranial magnetic stimulation
    1 Hertz stimulation for 16 minutes per day at 90% motor threshold, 5 sessions each to the two primary cortical targets

Primary Outcome Measures :
  1. Hallucination Change Score [ Time Frame: 2 weeks ]

Secondary Outcome Measures :
  1. Total AHRS score [ Time Frame: 2 weeks ]
  2. CGI [ Time Frame: 2 weeks ]
  3. Frequency subscale of AHRS [ Time Frame: 2 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Have persistent auditory hallucinations

Exclusion Criteria:

  • History of neurological disorder
  • Serious, unstable medical conditions (persons with hypertension or diabetes mellitus may enroll if these conditions are treated and stable)
  • Active drug or alcohol abuse (persons may enroll if they have a history of drug or alcohol abuse provided that they do not use these substances at least 4 weeks prior to study initiation)
  • History of seizures unrelated to drug withdrawal
  • Estimated IQ less than 80
  • Have a sibling or parent with epilepsy
  • Disorganized thought process or intellectual impairment that inhibits the ability to give an informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00042159

United States, Connecticut
Yale-New Haven Psychiatric Hospital
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
National Institute of Mental Health (NIMH)

Additional Information:
Publications of Results:
Other Publications:
Responsible Party: Ralph Edward Hoffman, Principal Investigator, Yale University Identifier: NCT00042159     History of Changes
Other Study ID Numbers: R21MH063326 ( U.S. NIH Grant/Contract )
R21MH063326 ( U.S. NIH Grant/Contract )
First Posted: July 26, 2002    Key Record Dates
Last Update Posted: August 6, 2013
Last Verified: August 2013

Keywords provided by Ralph Edward Hoffman, Yale University:
Auditory hallucinations (voices)

Additional relevant MeSH terms:
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms