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Successful use of maintenance rTMS for 8 months in a patient with antipsychotic-refractory auditory hallucinations
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Schizophrenia Research 100 (2008) 351 – 352 www.elsevier.com/locate/schres
Letter to the Editors Successful use of maintenance rTMS for 8 months in a patient with antipsychotic-refractory auditory hallucinations 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, 0920-9964/$ - see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2008.01.003
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 b2 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. 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 ReyOsterrieth 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
352
Letter to the Editors
Fig. 1. Improvement in different characteristics of the auditory hallucinations across 8 weeks of treatment.
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 medicationrefractory auditory hallucinations attenuate with a course of rTMS. References Aleman, A., Sommer, I.E., Kahn, R.S., 2007. Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: a meta-analysis. J. Clin. Psychiatry 68 (3), 416–421. Fitzgerald, P.B., Benitez, J., Daskalakis, J.Z., De Castella, A., Kulkarni, J., 2006. The treatment of recurring auditory hallucinations in schizophrenia with rTMS. World J. Biol. Psychiatry 7 (2), 119–122. Hoffman, R.E., Gueorguieva, R., Hawkins, K.A., Varanko, M., Boutros, N.N., Wu, Y.T., Carroll, K., Krystal, J.H., 2005. Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol. Psychiatry 58 (2), 97–104. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13 (2), 261–276.
Poulet, E., Brunelin, J., Kallel, L., Bediou, B., Dalery, J., D'Amato, T., Saoud, M., 2006. Is rTMS efficient as a maintenance treatment for auditory verbal hallucinations? A case report. Schizophr. Res. 84 (1), 183–184. Tharayil, B.S., Gangadhar, B.N., Thirthalli, J., Anand, L., 2005. Seizure with single-pulse transcranial magnetic stimulation in a 35year-old otherwise-healthy patient with bipolar disorder. J. ECT. 21 (3), 188–189.
Jagadisha Thirthalli* Balaji Bharadwaj Sandip Kulkarni Bangalore N. Gangadhar Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore-560029, India E-mail address: [email protected] (J. Thirthalli). ⁎ Corresponding author. Tel.: +91 8026995350; fax: +91 8026564830. Saifuddin Kharawala Chittaranjan Andrade Department of Psychopharmacology, National Institute of Mental Health And Neurosciences, Hosur Road, Bangalore-560029, India
29 September 2007
Schizophrenia Research 100 (2008) 351 – 352 www.elsevier.com/locate/schres
Letter to the Editors Successful use of maintenance rTMS for 8 months in a patient with antipsychotic-refractory auditory hallucinations 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, 0920-9964/$ - see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2008.01.003
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 b2 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. 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 ReyOsterrieth 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
352
Letter to the Editors
Fig. 1. Improvement in different characteristics of the auditory hallucinations across 8 weeks of treatment.
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 medicationrefractory auditory hallucinations attenuate with a course of rTMS. References Aleman, A., Sommer, I.E., Kahn, R.S., 2007. Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: a meta-analysis. J. Clin. Psychiatry 68 (3), 416–421. Fitzgerald, P.B., Benitez, J., Daskalakis, J.Z., De Castella, A., Kulkarni, J., 2006. The treatment of recurring auditory hallucinations in schizophrenia with rTMS. World J. Biol. Psychiatry 7 (2), 119–122. Hoffman, R.E., Gueorguieva, R., Hawkins, K.A., Varanko, M., Boutros, N.N., Wu, Y.T., Carroll, K., Krystal, J.H., 2005. Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol. Psychiatry 58 (2), 97–104. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13 (2), 261–276.
Poulet, E., Brunelin, J., Kallel, L., Bediou, B., Dalery, J., D'Amato, T., Saoud, M., 2006. Is rTMS efficient as a maintenance treatment for auditory verbal hallucinations? A case report. Schizophr. Res. 84 (1), 183–184. Tharayil, B.S., Gangadhar, B.N., Thirthalli, J., Anand, L., 2005. Seizure with single-pulse transcranial magnetic stimulation in a 35year-old otherwise-healthy patient with bipolar disorder. J. ECT. 21 (3), 188–189.
Jagadisha Thirthalli* Balaji Bharadwaj Sandip Kulkarni Bangalore N. Gangadhar Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore-560029, India E-mail address: [email protected] (J. Thirthalli). ⁎ Corresponding author. Tel.: +91 8026995350; fax: +91 8026564830. Saifuddin Kharawala Chittaranjan Andrade Department of Psychopharmacology, National Institute of Mental Health And Neurosciences, Hosur Road, Bangalore-560029, India
29 September 2007