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J Neurol Neurosurg Psychiatry 67:129-130 doi:10.1136/jnnp.67.1.129
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Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: a pilot study

  1. E COHEN,
  2. M BERNARDO,
  3. J MASANA,
  4. F J ARRUFAT,
  5. V NAVARRO
  1. Department of Psychiatry
  2. Department of Neurophysiology
  3. Department of Psychology
  4. Department of Nuclear Medicine
  5. Institut d’ Investigacions Biomédiques August Pi i Sunyer, Hospital Clínic i Provincial. Universitat de Barcelona, Spain
  1. Dr M Bernardo, Servicio de Psiquiatría, Hospital Clínic i Provincial, Villarroel 170, 08036 Barcelona, Spain. Telephone 00343 2275400, ext 2405; fax 00 343 2275477; email bernardo{at}medicina.ub.es
  1. J VALLS-SOLÉ
  1. Department of Psychiatry
  2. Department of Neurophysiology
  3. Department of Psychology
  4. Department of Nuclear Medicine
  5. Institut d’ Investigacions Biomédiques August Pi i Sunyer, Hospital Clínic i Provincial. Universitat de Barcelona, Spain
  1. Dr M Bernardo, Servicio de Psiquiatría, Hospital Clínic i Provincial, Villarroel 170, 08036 Barcelona, Spain. Telephone 00343 2275400, ext 2405; fax 00 343 2275477; email bernardo{at}medicina.ub.es
  1. T BOGET,
  2. N BARRANTES,
  3. S CATARINEU,
  4. M FONT
  1. Department of Psychiatry
  2. Department of Neurophysiology
  3. Department of Psychology
  4. Department of Nuclear Medicine
  5. Institut d’ Investigacions Biomédiques August Pi i Sunyer, Hospital Clínic i Provincial. Universitat de Barcelona, Spain
  1. Dr M Bernardo, Servicio de Psiquiatría, Hospital Clínic i Provincial, Villarroel 170, 08036 Barcelona, Spain. Telephone 00343 2275400, ext 2405; fax 00 343 2275477; email bernardo{at}medicina.ub.es
  1. F J LOMEÑA
  1. Department of Psychiatry
  2. Department of Neurophysiology
  3. Department of Psychology
  4. Department of Nuclear Medicine
  5. Institut d’ Investigacions Biomédiques August Pi i Sunyer, Hospital Clínic i Provincial. Universitat de Barcelona, Spain
  1. Dr M Bernardo, Servicio de Psiquiatría, Hospital Clínic i Provincial, Villarroel 170, 08036 Barcelona, Spain. Telephone 00343 2275400, ext 2405; fax 00 343 2275477; email bernardo{at}medicina.ub.es

    Recently, a new technology known as repetitive transcranial magnetic stimulation (RTMS) has been developed.1 In 1994, the use of magnetic stimulation in clinical psychiatry was suggested.2 Since then, it has been used in the study or treatment of obsessive-compulsive disorder, conversion disorder, schizophrenia, and particularly, depression.3

    Our pilot study aimed to assess the possible adverse effects of this treatment in chronic schizophrenic patients with severe negative symptoms; to evaluate if direct RTMS of the prefrontal cortex might improve negative symptoms or cognitive impairments4 in patients with chronic schizophrenia; and thirdly, to note if RTMS might modify the deficit in prefrontal cortical activity, often referred to as hypofrontality, long established in schizophrenia,5specially under conditions of task activation.

    Six right handed patients with chronic schizophrenia were identified at the outpatient psychiatric service of the Hospital Clínic of Barcelona. There were two men and four women (mean age 39).

    Exclusion criteria included alcohol or substance abuse dependence disorder in the past 5 years, focal neurological findings, systemic neurological illness, taking cerebral metabolic activator or vasodilator medications, electroconvulsive therapy within 6 months, and significant abnormal findings on laboratory examination.

    All patients were taking neuroleptic drugs, but a stable dose for at least 3 months was required. All patients were studied off benzodiazepines for at least 1 week before beginning the treatment. During the RTMS, psychotropic medications were continued at the initial dosage.

    All patients were admitted to hospital. Inpatients underwent the UKU side effects scale,6 the positive and negative syndrome scale (PANSS), and a neuropsychological battery, the day before beginning the treatment and at the end of the treatment. The UKU scale was also administered after each session.

    An equivalent neuropsychological battery was used on both occasions, which consisted of the block design subtest of the Wechsler adult intelligence scale, the trail making tests A and B, the FAS verbal fluency test, and two subtests of the Wechsler memory scale (the visual memory reproduction and the verbal paired associates subtests).

    A brain SPECT study was performed using a rotating dual head gamma camera, fitted with high resolution fanbeam collimators. Two99mTc-HMPAO SPECT scans with cognitive activation, such as the Wisconsin card sorting test (WCST), were performed on each patient (24 hours before the beginning of the treatment and 24 hours after the last session).

    RTMS was given with a Mag Pro magnetic stimulator, 5 days a week, during 2 weeks, at a dosage of 20 Hz for 2 seconds, once per minute for 20 minutes at 80% motor threshold. The motor threshold was determined by visualisation of finger movement. A butterfly magnetic coil was placed tangential to the orbital area, on the C3 and C4 EEG point.

    An important finding of this study was that RTMS may be given to stable schizophrenic patients without exacerbating their psychoses. All patients tolerated the RTMS well, with minimal side effects (mild headache and tinnitus).

    Initial SPECT of one patient was reported to be normal, showing no evidence of hypofrontality. The remainder of the patients showed hypofrontality on the initial neuroimaging. The results after RTMS indicated no change in the hypofrontality.

    Negative symptoms showed a general decrease for all patients (table). Significance (p<0.02) was noted on the PANSS negative symptoms subscale. These patients seemed to be more sociable than when originally seen. Nevertheless, clinical effects of the RTMS were subtle and difficult to distinguish from those derived from the supportive environment of the psychiatric ward.

    With regard to the neuropsychological battery, we found a general improvement in all post-treatment scores (table), but only delayed visual memory achieved significance (p<0.05). This feature might be basically explained by improvement of attention, specifically of the maintenance of attention, which allows the correct function of the working memory. Thus, although there are methodological limitations regarding the power of our conclusions, it is certain that there has been an improvement in the attentional capability.

    Table  Neuropsychological tests and PANSS scores

    We found that all patients (except one, who was always within the normal range) diminished their number of perseverative answers and errors on WCST (items characteristically altered in schizophrenia) after the RTMS. However, significance was not achieved on any WCST scores.

    Two patients who initially did not perform any categories on WCST, after the treatment, achieved one category, a possible indication of improvement of their abstract thinking. This change leads us to consider a research strategy previously reported, in which the WCST is used as a screening test for selecting schizophrenic patients. Those initially achieving low category scores would be compared to higher category scorers in an effort to identify a subgroup most likely to benefit from RTMS.

    Taking into account these mild improvements together, and the lack of changes in hypofrontality after treatment, we are considering extending the treatment course to 20 sessions, each at 30 Hz for 1 second, at 90% of motor threshold. It was also suggested that other positions of the coil and other kinds of coils might give better results.

    The clinical change in our cohort after the RTMS could be attributed to both the treatment and the supportive environment of the psychiatric ward, and even to enhance compliance to medication during hospital admission. We are aware that the small sample size and lack of controls compel a very careful interpretation of the results. Nevertheless, in the light of these, we suggest further controlled studies of the efficacy of RTMS in negative symptoms of schizophrenia, not only as an add on technique but also as a sole therapeutic procedure. Research on RTMS also requires some controlled studies aimed to the complexity of the methodology (dosage, duration, and localisation), as this form of intervention may prove to be an economical and convenient therapy in treating several psychiatric disorders.

    References

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