East Asian Arch Psychiatry 2017;27:162-4
Case Report
Feasibility and Clinical Utility of High-definition Transcranial Direct Current Stimulation in the Treatment of Persistent Hallucinations in Schizophrenia A Bose, V Shivakumar, H Chhabra, R Parlikar, VS Sreeraj, D Dinakaran, JC Narayanaswamy, G Venkatasubramanian
Abstract Persistent auditory verbal hallucination is a clinically significant problem in schizophrenia. Recent studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in treatment. An optimised version of tDCS, namely high-definition tDCS (HD-tDCS), uses smaller electrodes arranged in a 4x1 ring configuration and may offer more focal and predictable neuromodulation than conventional tDCS. This case report illustrates the feasibility and clinical utility of add-on HD-tDCS over the left temporoparietal junction in a 4x1 ring configuration to treat persistent auditory verbal hallucination in schizophrenia. Key words: Hallucinations; Schizophrenia; Transcranial direct current stimulation
Dr Anushree Bose, PhD, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Dr Venkataram Shivakumar, MBBS, PhD, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Ms Harleen Chhabra, BTech, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Dr Rujuta Parlikar, MBBS, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Dr Vanteemar S. Sreeraj, MD, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Dr Damodharan Dinakaran, MD, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Dr Janardhanan C. Narayanaswamy, MD, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Prof. Ganesan Venkatasubramanian, MD, PhD, WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Address for correspondence: Prof. Ganesan Venkatasubramanian, Professor of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore 560029, India. Email:
[email protected] Submitted: 20 February 2017; Accepted: 22 August 2017
Introduction Auditory verbal hallucination (AVH) persists in about 30% of schizophrenic patients despite adequate treatment with antipsychotics. Add-on treatment with conventional transcranial direct current stimulation (tDCS) that uses rectangular electrodes of 35 cm2 has been found to be clinically effective in ameliorating persistent AVH among schizophrenia.1 Conventional tDCS modulates cortical areas wider than intended. Moreover, the largest cortical 162
current density might not be localised directly under the target electrode. These factors may contribute to the inconsistent observations on the effect of add-on tDCS for AVH in schizophrenia.2 Contextually, it has been suggested that high-definition tDCS (HD-tDCS) that uses smaller electrodes arranged in a 4x1 ring configuration may offer more focal and predictable neuromodulation than conventional tDCS; hence, HD-tDCS might be advantageous to evaluate the contribution of specific cortical areas to cognition / behaviour as well as have clinical benefit.3 In this case report, we describe the feasibility and clinical utility of add-on HD-tDCS in a 4x1 ring configuration to the left temporoparietal junction (TPJ) to ameliorate persistent AVH in schizophrenia.
Case Report A 28-year-old right-handed male with schizophrenia (diagnosed by the DSM-5) experienced second-person AVHs in the form of instructions and command hallucinations from a well-renowned saint who had died several decades ago. Apart from hearing the saint’s voice, the patient saw the saint every day and had been communicating with him almost continuously over the last 5 years. His parents corroborated the hallucinations experienced by the patient and confirmed his hallucinatory behaviour. Since 2011, the patient had been treated with an adequate trial of olanzapine without any significant improvement. He had no other co-morbid psychiatric diagnosis including substance use disorders. The patient presented to us in December 2016 with persistent and severe AVH, command hallucinations, visual hallucinations, and violent visual imagery upon © 2017 Hong Kong College of Psychiatrists
Treatment of Persistent Hallucinations in Schizophrenia
closing of the eyes. He had been treated with a combination of risperidone (3 mg/day) and olanzapine (10 mg/day) for at least the last 3 months. His AVH score assessed by the Psychotic Symptom Rating Scales–Auditory Hallucination subscale (PSYRATS-AH)4 was 32 with a high score for items related to frequency of voice, negative content, and distress. His positive symptom score was 48 as assessed by the Scale for Assessment of Positive Symptoms (SAPS) and negative symptom score as assessed by the Scale for Assessment of Negative Symptoms (SANS) was 29. In view of the persistent AVHs, he was offered the option of add-on HD-tDCS on an outpatient basis. The patient and his primary caregivers (parents) were provided with adequate information about HD-tDCS and a video of the procedure was also shown to them; after this, the patient and his parents provided written informed consent for HD-tDCS treatment. High-definition tDCS was administered using standard equipment (Soterix Medical MxN HD system; http://soterixmedical.com/mxn.php) as per previous description (https://www.jove.com/video/50309/techniqueconsiderations-use-4x1-ring-high-definition-transcranial)5 using stringent safety measures. The MxN HD-tDCS system offers a technical enhancement with optimised electrodes and montage configurations that substantially increase the focality of stimulation. In this HD-tDCS protocol, we used a 4x1 ring electrode montage to deliver -1.5 mA of direct current for 20 minutes to the left TPJ. Five sintered Ag/AgCl ring electrodes (outer radius 12 mm, inner radius 6 mm) were arranged on the scalp with the aid of an electroencephalographic (EEG) cap (10-10 system electrode placement) and plastic casing to secure the electrode positions. The central electrode, designated as cathode, was placed at CP5 as per 10-10 montage of EEG electrode placement system, and injected with -1.5 mA. This electrode was surrounded by 4 return electrodes (C5, TP7,
Figure. Schematic depiction of HD-tDCS montage used for treating auditory verbal hallucinations. (Central cathode: CP5; return anodes: C5, CP3, P5, TP7)
Abbreviation: HD-tDCS = high-definition transcranial direct current stimulation. East Asian Arch Psychiatry 2017, Vol 27, No.4
CP3, P5) that were each injected with a current intensity of +0.38 mA (Fig). The patient was requested to relax, remain calm during the session and not to interact with the HD-tDCS administrator throughout the duration of session unless he felt any side-effects. Two sessions of 20 minutes each per day, scheduled 3 hours apart were administered for 5 consecutive days. At the end of each session, a structured questionnaire was used to assess any potential adverse effect that might have occurred either during or after the HD-tDCS session. After receiving 10 sessions of HD-tDCS, there was a significant reduction (37%) in PSYRATS-AH scores (from 32 to 20). Besides a reduction in frequency of voices, the patient also reported a decrease in amount and degree of negative content, weakening of visual hallucinations of the saint, complete absence of violent imagery on closing of his eyes, and better control over the voices. His SAPS score decreased to 38 and SANS score decreased to 15. He was also able to sleep better, relax, and engage with his environment without any distress due to reduced symptoms. This subjective improvement was corroborated by the parents in terms of a remarkable reduction in his hallucinatory behaviour. Both the patient and his caregivers acknowledged that the clinical improvement consequent to HD-tDCS was the best achieved during the entire course of the illness since the onset of symptoms in 2011. Follow-up by telephone with the patient and his parents revealed that the improvement was maintained after 4 weeks. During the course of HD-tDCS and over the next 4 weeks, no change had been made to the patient’s medications.
Discussion To the best of our knowledge, this is the first report of application of HD-tDCS in schizophrenia to describe the feasibility and clinical utility of add-on HD-tDCS over the left TPJ in a 4x1 ring configuration to treat persistent AVH in schizophrenia. In our patient, we observed rapid amelioration of distressing AVH, visual hallucinations, and visual imagery with add-on HD-tDCS. The magnitude of reduction in AVH score was in line with the reported beneficial effects of conventional tDCS studies.1 All sessions were very well tolerated by the patient and he reported no adverse effects either during or after HD-tDCS. Our observation supports add-on HD-tDCS as a promising treatment for persistent symptoms of schizophrenia that do not respond well to antipsychotic treatment. Safe add-on treatment options like HD-tDCS have potential clinical utility given the side-effects associated with medications such as clozapine (especially in patients who have poor tolerance) to treat antipsychotic-resistant symptoms in schizophrenia.6 We did not assess the cognitive function in this patient; this would have revealed potential effects of HD-tDCS on cognition. Future research is needed in this area. In addition, the efficacy of add-on HD-tDCS as well as its comparative profile with conventional tDCS needs rigorous assessment in a large sample of schizophrenic 163
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patients using a randomised, sham-controlled design. In addition, better focality of stimulation with HD-tDCS prompts for systematic studies to examine the mechanism of improvement in AVH with HD-tDCS in schizophrenia.
Acknowledgements This work was supported by the Department of Science and Technology, Government of India (DST/SJF/LSA-02/ 2014-15) to Dr Anushree Bose and Dr Rujuta Parlikar. Dr Venkataram Shivakumar was supported by the Indian Council of Medical Research (DHR/HRD/Young Scientist/ Type-VI-[2]/2015). Ms Harleen Chhabra was supported by the Department of Biotechnology, Government of India.
Declaration All authors have disclosed no conflicts of interest.
References 1. Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, SuaudChagny MF, et al. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry 2012;169:719-24. 2. Fitzgerald PB, McQueen S, Daskalakis ZJ, Hoy KE. A negative pilot study of daily bimodal transcranial direct current stimulation in schizophrenia. Brain Stimul 2014;7:813-6. 3. Kuo HI, Bikson M, Datta A, Minhas P, Paulus W, Kuo MF, et al. Comparing cortical plasticity induced by conventional and highdefinition 4 × 1 ring tDCS: a neurophysiological study. Brain Stimul 2013;6:644-8. 4. Haddock G, McCarron J, Tarrier N, Faragher EB. Scales to measure dimensions of hallucinations and delusions: the psychotic symptom rating scales (PSYRATS). Psychol Med 1999;29:879-89. 5. Villamar MF, Volz MS, Bikson M, Datta A, Dasilva AF, Fregni F. Technique and considerations in the use of 4 × 1 ring high-definition transcranial direct current stimulation (HD-tDCS). J Vis Exp 2013;(77):e50309. 6. Grover S, Hazari N, Chakrabarti S, Avasthi A. Association of clozapine with seizures: A brief report involving 222 patients prescribed clozapine. East Asian Arch Psychiatry 2015;25:73-8.
Acknowledgements The Editorial Board of East Asian Archives of Psychiatry wishes to thank the reviewers for volunteering their expertise and insight, and for their hard work and diligence in reviewing articles for the year 2017. 164
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