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A case report of cTBS for the treatment of auditory hallucinations in a patient with schizophrenia
Brain Stimulation (2009) 2, 118–9
www.brainstimjrnl.com
LETTER TO THE EDITOR A case report of cTBS for the treatment of auditory hallucinations in a patient with schizophrenia To the Editor: A recent meta-analysis1 concluded that 1Hz repetitive transcranial magnetic stimulation (rTMS) efficiently reduces resistant auditory hallucinations in patients with schizophrenia (effect size 5 0.76). Nevertheless, published studies have only described treatment over short periods, and little is known about the longer-term impact of TMS on hallucinations. Maintenance treatment protocols have been developed,2 but little is known about optimal parameters (for the acute treatment as well as for maintenance). Recently, Huang et al3 showed that a continuous theta burst stimulation (cTBS) protocol used to induce long-term depression in brain slices can be adapted to a TMS protocol to rapidly produce long-lasting, but reversible effects on motor cortex physiology and behavior. In this case, we tested the efficacy and the safety of cTBS for the treatment of auditory hallucinations in a patient with schizophrenia. We hypothesized that cTBS could be as effective and safe as 1 Hz rTMS stimulation with a time of stimulation 30 times shorter. ‘‘Mr. D,’’ a 40-year-old right-handed inpatient with DSMIV schizophrenia was referred for TMS treatment. He had been having from resistant auditory hallucinations for 20 years (frequent and loud) despite prescription of at least 4 optimal antipsychotic trials (more than 4 months at high dose for each). A detailed assessment did not reveal any other disease or TMS contraindications. Auditory hallucinations (AH) were assessed by using the Auditory Hallucination Rating Scale (AHRS - 4) and the patient had a score of 35 at baseline (range of the scale: 2-40). The patient gave informed consent and was included in a TMS protocol. His current dose of antipsychotic medication (risperidone, 8 mg/ d), was maintained during treatment and a twice-a-day TMS regimen (one session in the morning, the other in the afternoon), about 17 minutes of 1000 low-frequency repetitive stimulations (1 Hz) was administered to the temporoparietal cortex at 100% of motor threshold over a 5-day period (170 minutes of ‘‘on stimulation’’ per week). Stimulations were carried out to the left temporoparietal cortex with a Medtronic Mag PRO (Medtronic, Boulogne, France) stimulator system, with liquid-cooled figure-eight 1935-861X/09/$ -see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.brs.2008.09.008
70-mm coils. An appropriately sized lycra cap was placed on the head to enable marking of the TMS coil position. The location of stimulation was given halfway between the left temporal (T3) and left parietal (P3) electroencephalogram electrode sites on the basis of the international 10-20 placement system as described by Hoffman et al.4 Coil position was stabilized with a mechanical arm. The patient was instructed to be as relaxed as possible during the course. After the first course, auditory hallucinations were improved, with a 50% reduction in his AHRS score, which worsened to 70% of the initial score 3 weeks after the end of rTMS treatment. One month later a new rTMS 5-day acute course, with the same parameters, was conducted. AH were again improved with a 50% reduction in AHRS and 3 weeks later, without any maintenance TMS, AH reoccurred (70% again). Thus, as the AH seemed to reoccur about 3 weeks after the rTMS treatments, we decided to treat the patient by a once-a-week-per-month, twice-daily maintenance protocol. The patient’s AH were improved by 50% with no change over the next 4 months. We decided to reduce the number of sessions and a-week-per-month, once-daily maintenance protocol was delivered. We observed an improvement to 50% of AHRS during 5 months but the sixth month, AH worsen again to 70% of the initial score. We decided to change the stimulation parameters and to deliver twice-daily 600 stimulations over 5 days (6 minutes and 40 seconds of ‘‘on stimulation’’ per week) of cTBS at 80% of motor threshold (cTBS: 40-second train of uninterrupted 3 pulses of stimulation at 50 Hz repeated every 200 milliseconds). This protocol was well tolerated by the patient. After a week of treatment, AH were improved again with a 50% reduction in AHRS score and this effect continued during the 2 months that followed the acute response. Our case raises the question as to whether twice-daily cTBS may be useful in some patients as a possible maintenance intervention. Ten cTBS trains of 40 seconds seemed to be as effective as ten 1-Hz rTMS trains of 20 minutes with no side effects, for a total duration of stimulation 25 times shorter and with a less intensity (80 vs 100% of motor threshold). Moreover, as described by Huang et al3 this effect could remain longer than with the low frequency, although this is not yet documented or known in this patient. Certainly, further research will help
Letter to the editor us to understand whether the benefits observed in this single case report of cTBS TMS for AH might also be evident in larger studies and as an acute treatment. Emmanuel Poulet, MD, PhD Jerome Brunelin, PhD* Wissem Ben Makhlouf, MD Thierry D’Amato, MD, PhD Mohamed Saoud, MD, PhD EA 4166 Universite´ Lyon CH Le Vinatier 95 boulevard Pinel Bron 69677 France *E-mail address: [email protected]
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References 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. Poulet E, Brunelin J, Kallel L. D’Amato T, Saoud M. Maintenance treatment with transcranial magnetic stimulation in a patient with late-onset schizophrenia. Am J Psychiatry 2008;165:537-538. 3. Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwel JC. Theta burst stimulation of the human motor cortex. Neuron 2005;45: 201-206. 4. Hoffman RE, Hawkins KA, Gueorguieva R, et al. Transcranial magnetic stimulation of left temporoparietal cortex and medicationresistant auditory hallucinations. Arch Gen Psychiatry 2003;60: 49-56.
www.brainstimjrnl.com
LETTER TO THE EDITOR A case report of cTBS for the treatment of auditory hallucinations in a patient with schizophrenia To the Editor: A recent meta-analysis1 concluded that 1Hz repetitive transcranial magnetic stimulation (rTMS) efficiently reduces resistant auditory hallucinations in patients with schizophrenia (effect size 5 0.76). Nevertheless, published studies have only described treatment over short periods, and little is known about the longer-term impact of TMS on hallucinations. Maintenance treatment protocols have been developed,2 but little is known about optimal parameters (for the acute treatment as well as for maintenance). Recently, Huang et al3 showed that a continuous theta burst stimulation (cTBS) protocol used to induce long-term depression in brain slices can be adapted to a TMS protocol to rapidly produce long-lasting, but reversible effects on motor cortex physiology and behavior. In this case, we tested the efficacy and the safety of cTBS for the treatment of auditory hallucinations in a patient with schizophrenia. We hypothesized that cTBS could be as effective and safe as 1 Hz rTMS stimulation with a time of stimulation 30 times shorter. ‘‘Mr. D,’’ a 40-year-old right-handed inpatient with DSMIV schizophrenia was referred for TMS treatment. He had been having from resistant auditory hallucinations for 20 years (frequent and loud) despite prescription of at least 4 optimal antipsychotic trials (more than 4 months at high dose for each). A detailed assessment did not reveal any other disease or TMS contraindications. Auditory hallucinations (AH) were assessed by using the Auditory Hallucination Rating Scale (AHRS - 4) and the patient had a score of 35 at baseline (range of the scale: 2-40). The patient gave informed consent and was included in a TMS protocol. His current dose of antipsychotic medication (risperidone, 8 mg/ d), was maintained during treatment and a twice-a-day TMS regimen (one session in the morning, the other in the afternoon), about 17 minutes of 1000 low-frequency repetitive stimulations (1 Hz) was administered to the temporoparietal cortex at 100% of motor threshold over a 5-day period (170 minutes of ‘‘on stimulation’’ per week). Stimulations were carried out to the left temporoparietal cortex with a Medtronic Mag PRO (Medtronic, Boulogne, France) stimulator system, with liquid-cooled figure-eight 1935-861X/09/$ -see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.brs.2008.09.008
70-mm coils. An appropriately sized lycra cap was placed on the head to enable marking of the TMS coil position. The location of stimulation was given halfway between the left temporal (T3) and left parietal (P3) electroencephalogram electrode sites on the basis of the international 10-20 placement system as described by Hoffman et al.4 Coil position was stabilized with a mechanical arm. The patient was instructed to be as relaxed as possible during the course. After the first course, auditory hallucinations were improved, with a 50% reduction in his AHRS score, which worsened to 70% of the initial score 3 weeks after the end of rTMS treatment. One month later a new rTMS 5-day acute course, with the same parameters, was conducted. AH were again improved with a 50% reduction in AHRS and 3 weeks later, without any maintenance TMS, AH reoccurred (70% again). Thus, as the AH seemed to reoccur about 3 weeks after the rTMS treatments, we decided to treat the patient by a once-a-week-per-month, twice-daily maintenance protocol. The patient’s AH were improved by 50% with no change over the next 4 months. We decided to reduce the number of sessions and a-week-per-month, once-daily maintenance protocol was delivered. We observed an improvement to 50% of AHRS during 5 months but the sixth month, AH worsen again to 70% of the initial score. We decided to change the stimulation parameters and to deliver twice-daily 600 stimulations over 5 days (6 minutes and 40 seconds of ‘‘on stimulation’’ per week) of cTBS at 80% of motor threshold (cTBS: 40-second train of uninterrupted 3 pulses of stimulation at 50 Hz repeated every 200 milliseconds). This protocol was well tolerated by the patient. After a week of treatment, AH were improved again with a 50% reduction in AHRS score and this effect continued during the 2 months that followed the acute response. Our case raises the question as to whether twice-daily cTBS may be useful in some patients as a possible maintenance intervention. Ten cTBS trains of 40 seconds seemed to be as effective as ten 1-Hz rTMS trains of 20 minutes with no side effects, for a total duration of stimulation 25 times shorter and with a less intensity (80 vs 100% of motor threshold). Moreover, as described by Huang et al3 this effect could remain longer than with the low frequency, although this is not yet documented or known in this patient. Certainly, further research will help
Letter to the editor us to understand whether the benefits observed in this single case report of cTBS TMS for AH might also be evident in larger studies and as an acute treatment. Emmanuel Poulet, MD, PhD Jerome Brunelin, PhD* Wissem Ben Makhlouf, MD Thierry D’Amato, MD, PhD Mohamed Saoud, MD, PhD EA 4166 Universite´ Lyon CH Le Vinatier 95 boulevard Pinel Bron 69677 France *E-mail address: [email protected]
119
References 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. Poulet E, Brunelin J, Kallel L. D’Amato T, Saoud M. Maintenance treatment with transcranial magnetic stimulation in a patient with late-onset schizophrenia. Am J Psychiatry 2008;165:537-538. 3. Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwel JC. Theta burst stimulation of the human motor cortex. Neuron 2005;45: 201-206. 4. Hoffman RE, Hawkins KA, Gueorguieva R, et al. Transcranial magnetic stimulation of left temporoparietal cortex and medicationresistant auditory hallucinations. Arch Gen Psychiatry 2003;60: 49-56.