Successful use of maintenance rTMS for 8 months in a patient with antipsychotic-refractory auditory hallucinations
Article Outline
Dear Editors,
There is evidence that 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the left temporoparietal cortex attenuates antipsychotic-resistant auditory hallucinations (Aleman et al., 2007). In many patients, hallucinations reappear within weeks of stopping treatment (Hoffman et al., 2005). The response to reinstitution of rTMS has been mixed (Fitzgerald et al., 2006, Poulet et al., 2006). Surprisingly, there are no reports of continuation of rTMS in patients who respond to treatment. We report a patient whose medication-resistant auditory hallucinations remitted with rTMS. Improvement was maintained with ‘maintenance’ rTMS.
1. Case report
Ms R, a 22-year-old student, experienced prominent and distress-provoking auditory hallucinations as part of a 3-year schizophrenic illness. The hallucinations were second- and third-person, commanding, commenting, and discussing voices. She also experienced thought echo. She had shown good response with aripiprazole (15 mg/day) and had been advised to continue it. However, she stopped medicines after a few months because she and her family considered that medicines were no longer necessary. About 5 months after stopping aripiprazole, she relapsed into psychosis. This time, she failed to respond to aripiprazole at the same dosage. Further trials of ziprasidone up to 160 mg/day, haloperidol [both oral (10 mg/day) and depot (50 mg every 3 weeks)] and olanzapine up to 15 mg/day, each for periods of 4–8 weeks failed to bring about substantial response. At this stage, clozapine was initiated and uptitrated to 250 mg/day. She responded partially but, because of sedation, the dose could not be further increased. After 11 months of clozapine monotherapy, risperidone augmentation (up to 4 mg/day) was prescribed with further benefit; however, distressing auditory hallucinations continued. The hallucinations currently lasted 5–15 min per occasion, 2–3 times per day. As 12 weeks of the clozapine-risperidone combination failed to stop hallucinations despite good compliance, rTMS was offered in August 2006.
The medications were continued, and rTMS (1 Hz, 100% motor threshold) was administered once daily, 5 times a week; the area chosen was halfway between T3 and P3 (Hoffman et al., 2005). Nine hundred pulses were delivered without interruption during each session. Hallucinations were rated on the hallucinatory behaviour item of PANSS (Kay et al., 1987) and on self-rated visual analogue scales for frequency, intensity, intrusiveness, duration and overall severity of hallucinations. There was substantial improvement after 2 weeks. With a view to reducing the known risk of relapse, and subsequent refractoriness to rTMS, treatment was continued, with her consent, once weekly for 6 weeks, once fortnightly for 6 fortnights and once monthly for 3 months. After week 4, she experienced near-total remission (Fig. 1); she heard voices for <
2 min only twice in 8 months. She maintains improvement on once monthly rTMS, has graduated, and is currently employed. She reported no adverse effects apart from mild headaches during rTMS sessions. Tapered withdrawal of risperidone midway during maintenance rTMS was uneventful; currently she continues to receive clozapine 250 mg/day.
Fig. 1.
Improvement in different characteristics of the auditory hallucinations across 8 weeks of treatment.
Neuropsychological assessments using tests of verbal, visual, and spatial learning and memory, scanning and perceptuomotor speed, and planning (Hopkins Verbal Learning Test, Digit Span, Letter-Number Sequencing, Spatial Span, Digit Symbol Substitution Test, Trail-Making Test Parts A and B, the Rey-Osterrieth test, Logical Memory test, Tower Of London test) were conducted before instituting maintenance rTMS; there was substantial improvement on almost all measures at 8 months.
2. Discussion
Reinstitution of rTMS after relapse has yielded mixed results (Fitzgerald et al., 2006, Poulet et al., 2006). We therefore prescribed maintenance rTMS for possibly the first time in literature to this clozapine-refractory patient with persistent auditory hallucinations. The hallucinations remitted with rTMS, and she has maintained improvement across 8 months of maintenance rTMS. There were no adverse effects such as cognitive impairments or seizures. This is pertinent because the cognitive safety of maintenance rTMS is unknown, and because clozapine lowers the seizure-threshold and seizures have been reported even with single-pulse TMS (Tharayil et al., 2005). We therefore suggest that 1 Hz maintenance rTMS over the left temporoparietal cortex be considered in patients whose medication-refractory auditory hallucinations attenuate with a course of rTMS.
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PII: S0920-9964(08)00050-9
doi:10.1016/j.schres.2008.01.003
© 2008 Elsevier B.V. All rights reserved.
