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Delayed response to repetitive transcranial magnetic stimulation treatment for intractable auditory hallucinations in schizoaffective disorder

David Kelly, BM, BS, FRANZCP, FaChAM

Ramsay Health Care (SA), Mental Health Services, The Adelaide Clinic, Gilberton, South Australia, Australia

Shane Gill, BMBS, FRANZCP, Dip. Psychother

Ramsay Health Care (SA), Mental Health Services, The Adelaide Clinic, Gilberton, South Australia, Australia

Patrick Clarke, MBBS, FRANZCP

Ramsay Health Care (SA), Mental Health Services, The Adelaide Clinic, Gilberton, South Australia, Australia

Cassandra Burton, B Psych. (Hons)

Ramsay Health Care (SA), Mental Health Services, The Adelaide Clinic, Gilberton, South Australia, Australia

Cherrie Galletly, MBChB, DPM, FRANZCP, PhD

The University of Adelaide, Northern Mental Health, Adelaide Health Service, The Adelaide Clinic, Gilberton, South Australia, Australia

KEYWORDS: transcranial magnetic stimulation, delayed response, auditory hallucinations



There have been a small number of treatment trials of low frequency repetitive transcranial magnetic stimulation (rTMS) to the left temporoparietal cortex for chronic, intractable auditory hallucinations (AHs).1 We report a possible “delayed response” to rTMS.

rTMS has been demonstrated to be an effective treatment for major depressive disorder (MDD).2 The availability of rTMS varies considerably in different countries. In 2008 the FDA approved the marketing of the NeuroStar TMS therapy device for treating adults with MDD who have failed to achieve satisfactory improvement with prior antidepressant medication.3 The use of rTMS to treat other conditions or symptoms, such as AHs, generally is regarded as experimental.


Ms. O, age 52, has a 16-year history of schizoaffective disorder. Her illness began with recurrent episodes of depression. Approximately 8 years ago she had a manic episode then subsequent episodes of mania treated with hospitalization, mood stabilizers, and atypical antipsychotics. In 2000 she became more floridly psychotic and the affective component of her illness became less prominent.

She presented with intense, disabling auditory hallucinations, present for 6 months. She described up to 36 different voices. The voices were people she knew and were not negative or derogatory, but sometimes did give commands. She did not have delusions, thought disorder, or mood symptoms. She had prominent negative symptoms and spent her time listening to the voices without engagement in any activities. There had been no response to a range of atypical antipsychotics. Clozapine had been considered but she was at risk of metabolic syndrome.

When referred for rTMS Ms. O had been taking paliperidone, 4 mg/d, amisulpride, 400 mg/d, lithium, 750 mg/d, and thyroxine, 50 mg/d, for 12 weeks. Her mental and physical health had been stable during this time. Thyroxine had been prescribed for many years. Menopause had occurred some years previously and she had no menopausal symptoms.

We adopted the protocol used by Lee et al,4 applying low frequency (1 Hz) rTMS for 20 minutes per day at 100% of the resting motor threshold to the left temporoparietal cortex, at scalp site TP3—located with an EEG cap. Initially, we proposed to treat Ms. O for 10 days, however, there was no response after 10 treatments so treatment was continued for another 10 days.

The Auditory Hallucination Rating Scale (AHRS), Awareness of Change Scale (ACS), and Positive and Negative Syndrome Scale (PANSS) were completed at baseline and at weeks 1, 2, 4, and 6. At baseline, Ms. O had an AHRS score of 34, PANSS score of 42, and a Hallucination Change Score (HCS) of 10. Posttreatment, her AHRS and HCS scores were reduced by 3 and 2 points, respectively. Her PANSS score had increased by 1 point. There had been little response to rTMS. She continued on her usual medications.

A follow-up assessment was conducted 40 days after Ms. O’s final rTMS treatment because her treating psychiatrist advised that Ms. O’s AHs had ceased. Ms. O reported that her AHs ceased approximately 1 month after the rTMS course ended. Her follow-up scores were AHRS, 0; HCS, 0; and PANSS, 20, with no change in negative symptoms. This appeared to be a delayed response to rTMS.

Previous studies have undertaken assessments at the beginning and end of treatment, so other cases of delayed response may have been missed. Other possibilities are that this was a very delayed response to the medications, or remission of symptoms as part of the natural course of the disorder. It has been suggested that rTMS is associated with neuronal changes5 which may take time, but it would be expected that symptomatic improvement would begin earlier. Baumer et al6 have demonstrated that rTMS may be associated with cumulative plastic changes in intrinsic motor cortex excitability, but a delay until after treatment has been completed would be unusual.

Chronic AHs are distressing and do not always respond well to either medication or psychological treatments. Repetitive TMS provides a safe, well-tolerated treatment, although it does require a time commitment by the patient. Currently rTMS is not widely available and generally is not reimbursed by state or private funding agencies. Our results, along with those of other studies cited, suggest that rTMS does have a place in the management of chronic, intractable AHs. Greater access to this treatment could benefit patients suffering from these distressing and disabling symptoms.

DISCLOSURE: The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.


  1. Aleman A, Sommer IE, Kahn RS. Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: a meta-analysis. J Clin Psychiatry. 2007;68:416–421.
  2. Slotema CW, Blom JD, Hoek HW, et al. Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry. 2010;71:873–884.
  3.  U.S. Food and Drug Administration. Neuronetics (510K) Summary Neurostar TMS Therapy System (2008). Published December 16, 2008. Accessed March 5, 2012.
  4. Lee SH, Kim W, Chung YC, et al. A double blind study showing that two weeks of daily repetitive TMS over the left or right temporoparietal cortex reduces symptoms in patients with schizophrenia who are having treatment-refractory auditory hallucinations. Neurosci Lett. 2005;376:177–181.
  5. Lisanby SH, Gutman D, Luber B, et al. Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. Biol Psychiatry. 2001;49:460–463.
  6. Bäumer T, Lange R, Liepert J, et al. Repeared premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans. Neuroimage. 2003;20:550–560.

CORRESPONDENCE: Cherrie Galletly, MBChB, DPM, FRANZCP, PhD, The University of Adelaide, Discipline of Psychiatry, The Adelaide Clinic Consulting Suites, 33 Park Terrace, Gilberton, South Australia 5081, Australia, E-MAIL: