Novel Use of Transcranial Direct Current Stimulation (tDCS) in Adolescents with Early Recovery Stage of Neuroleptic Malignant Syndrome or Catatonia

Abstract

There are limited options to treat psychotic symptoms during early recovery stage of neuroleptic malignant syndrome (NMS) and catatonic symptoms in adolescents because of restrictions on the use of electroconvulsive therapy (ECT). Add-on transcranial direct current stimulation (tDCS) treatment twice daily for five consecutive days showed improvement in auditory–visual hallucinations and cognitive and bio-social functioning during early recovery stages of NMS in an adolescent. The use of tDCS in another adolescent diagnosed with severe depressive episode with psychotic symptoms and catatonia showed improvement in staring, mutism, rigidity, and interaction with add-on tDCS. The improvement observed lasted for a short duration and tDCS treatment was well tolerated without any severe adverse effect.

Introduction

Transcranial direct current stimulation (tDCS) is an emerging neuromodulatory technique that administers low-intensity current through scalp electrodes to desired cortical regions. It is found to be safe, tolerable, and without any serious adverse effects in adults. ¹ In adults, it is effective in treating symptoms of major depressive episode without drug resistance, addiction, and craving and in reducing symptoms of schizophrenia, such as auditory verbal hallucinations and negative symptoms.^{2, 3} The number of studies of tDCS in adults has increased exponentially in the last few years, but there is limited research data in pediatric population. tDCS till date has been studied in neurotypical children and also for a range of neuropsychiatric disorders, such as cerebral palsy, language disorders, epilepsy, autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia.^4–9 In the only study of adolescents with a diagnosis of childhood onset schizophrenia, tDCS was found to be safe and tolerable in 12 subjects between 10 and 17 years of age and the most common adverse effect reported were tingling and itching over the scalp at electrode site. ⁹ Findings from the study of tDCS in adults with schizophrenia are encouraging with improvement noted in auditory verbal hallucinations, negative symptoms, and catatonic symptoms. ³ There are limited options, especially, to treat psychotic symptoms during symptomatic stage of neuroleptic malignant syndrome (NMS) and its early recovery period. Similarly, catatonic symptoms associated with psychotic disorders in adolescents have limited treatment options, wherein the treatment of primary psychiatric disorder is considered to be of utmost importance. Keeping in mind the lacunae in the available treatment, we considered using tDCS with a hypothesis that cathodal left temporo-parietal junction (TPJ) stimulation will reduce hallucinations during the recovery period of NMS, and anodal dorsolateral prefrontal cortex (DLPFC) stimulation will be helpful for negative/catatonic symptoms; hence, a uniform protocol of anode over left DLPFC and cathode over left temporo-parietal junction is used. Here, we describe the use of tDCS in treating psychotic symptoms during early recovery period of NMS and another young person with catatonic symptoms during a severe depressive episode, both the cases being part of a larger study to assess tolerability and clinical utility of tDCS. This is the first report of using tDCS in adolescents with early recovering stage of NMS and catatonia associated with depression to the best of our knowledge.

Case 1: Adolescent with Neuroleptic Malignant Syndrome

A 15-year-old girl studying in 10th grade presented with 8-week duration of symptoms characterized by delusions of persecution, third-person auditory verbal hallucinations, thought, and behavioral disorganization. She was diagnosed with paranoid schizophrenia according to The International Classification of Diseases 10th revision diagnostic criteria and treated initially with olanzapine up to 20 mg/day (p.o.) for 4 weeks. Subsequently, because of poor clinical response, olanzapine was stopped and risperidone 3 mg/day (p.o.) was initiated. After 4 weeks of treatment with risperidone, she developed hyperpyrexia (103-104 °F), rigidity, fluctuating blood pressure, and elevated creatine phosphokinase (CPK) characteristic of NMS (1104 U/L). Risperidone was discontinued and she was treated for NMS by a team of neurologist and pediatrician. Common organic causes, such as Wilson’s disease, autoimmune encephalitis, and neuroinfection, were ruled out. Oral lorazepam 4 mg/day, bromocriptine 3.75 mg/day, and baclofen 20 mg/day was used in the treatment of NMS with complete resolution of hyperpyrexia; however, hallucinations and delusions persisted leading to severe dysfunction. She continued to have severe psychopathology consisting of delusions of persecution, delusional misidentification, third-person auditory hallucinations, visual hallucinations, and thought and behavioral disorganization even after 2 weeks of NMS resolution (CPK levels normalized and absence of clinical features of NMS). Her symptom severity scores were as follows: auditory hallucinations: 41 (Auditory Hallucinations Rating Scale [AHRS]) ¹⁰ ; positive symptoms: 46 (Scale for Assessment of Positive Symptoms [SAPS]) ¹¹ ; and negative symptoms: 80 (Scale for Assessment of Negative Symptoms [SANS]) ¹² . Based on the potential risk for recurrence of NMS with antipsychotic re-challenge, tDCS was started after informed consent and assent were obtained as per the approval of the Institute Ethics Committee.

The trial of tDCS was administered using standard equipment (Neuroconn DC Stimulator Plus, http://www.neuroconn.de/dc-stimulator_plus_en/) as per previous description^{13, 14} with stringent safety measures. ¹⁵ 1 × 1 tDCS protocol was used with anode placed over a point midway between F3 and FP1 (left DLPFC) and the cathode located over a point midway between T3 and P3 (TPJ). The electrodes size was 25 cm ² and the stimulation level was set at 2 mA for 20 min. The sessions were conducted twice a day (separated by at least 3 h) for 5 consecutive days;^{13, 14} the first and second sessions of the day were administered in the morning and afternoon, respectively. No changes in medicines were made during this period. Local examination of scalp, mental status examination, and monitoring of vital parameters were conducted every day along with monitoring of adverse effects using a questionnaire given by Brunoni and colleagues. ¹⁵ Patient tolerated tDCS well, except for complaints of tolerable and transient burning sensation in the first 2 sessions. Clinically significant improvement in symptoms was observed after 10 sessions of tDCS, which was accompanied by reduction in distress because of auditory and visual hallucinations and improvement in biological and social functioning. Her symptom scores following tDCS were as follows: AHRS: 32; SAPS: 34; and SANS: 65. Neuropsychological assessments done before and after tDCS showed improvement in attention and auditory verbal learning. On visual analogue scale there was 5-point improvement (50%) reported by patient and parent. Clinical improvement was sustained for about a month; subsequently, changes in medication were required to achieve remission of symptoms.

Case 2: Adolescent with Catatonia

15-year-old right-handed young male, studying in 10th grade belonging to lower socioeconomic status with family history of bipolar affective disorder, committed suicide in second degree relative presented with 1 year duration of symptoms characterized by low mood, anhedonia, decreased social interaction, decreased sleep and appetite, suicidal gestures, and persecutory delusions. Inpatient observation for a period of 2 weeks revealed significant negative symptoms in the form of amotivation, alogia, and anhedonia. Catatonic symptoms, such as staring, mutism, rigidity, posturing, gegenhalten, and ambitendancy, were also present. He was provisionally diagnosed to have severe depressive episode with psychotic symptoms and catatonia according to The International Classification of Diseases 10th revision diagnostic criteria and treated with a combination of risperidone 4 mg/day (p.o.) and fluoxetine 20 mg/day (p.o.) for 12 weeks without much clinical improvement. Subsequent treatment included olanzapine 20 mg/day (p.o.), fluoxetine 20 mg/day (p.o.), and intravenous lorazepam up to 10 mg/day in 3 divided doses. Even though he received this treatment for more than 6 weeks, no substantial improvement was noticed. In this context, tDCS trial was given after informed consent and assent. 1 × 1 tDCS protocol was administered for 20 min twice daily for 5 consecutive days using the same parameters and electrode positions as in the first case. 10 sessions of tDCS were given in 5 days and no changes in medicines were made during this period. Overall, patient tolerated tDCS well and had only transient tingling sensation at electrode site in first 4 sessions. No other adverse effects were noticed. At the end of tDCS trial, a reduction in Bush-Francis catatonia rating scale (BFCRS) from 22/69 to 7/69 and SANS from 86 to 73 was noticed, while there was marginal increase in SAPS from 17 to 20. Observation in the ward revealed complete disappearance of staring, mutism, and rigidity, while substantial improvement in the interest in daily activities, interaction with others, and expression of psychopathology was noted. This later point could have contributed to elevation of SAPS score. No significant changes were observed on neuropsychological assessment and measures of illness such as children’s global assessment scale (CGAS) and clinical global impression (CGI). Subsequent to tDCS treatment, even though, significant improvement was present in catatonic and negative symptoms overall improvement in affective and psychotic symptoms was limited. Therefore, pharmacological changes were made to achieve remission of symptoms.

Discussion

This is the first report of using tDCS in adolescents for psychotic symptoms during NMS and catatonia of depressive episode. Even though NMS is uncommon, it is a life-threatening condition and its presentation and course in children and adolescents is overall similar to adults. ¹⁶ Treatment strategies suggested during NMS mainly involve discontinuing the suspected drug and supportive care. Subsequently, the use of low potency antipsychotics, slow titration, antipsychotic free period, and ECT are also recommended. ¹⁷ Being said that, little attention is paid to the management of psychotic symptoms during NMS and no guidelines exist about treating psychotic symptoms while having NMS and its immediate recovery period. tDCS when used in such an ambiguous situation may help reduce psychotic symptoms and provide the time window for re-challenge with antipsychotics. With regard to catatonia, there are a few reports of tDCS that are useful in reducing negative symptoms and catatonia associated with schizophrenia when applied over bilateral prefrontal cortices. ³ tDCS was successfully used as a replacement for weekly maintenance of ECT in a 41-year-old male patient with organic catatonia and corpus callosal agenesis. In this case report, tDCS was administered with anode over left DLPFC and cathode over right, with improvement in catatonia over 13 weeks treatment. ¹⁸ In another case report, tDCS applied over DLPFC in a 14-year-old girl with autism spectrum disorder and drug-resistant catatonia resulted in improvement of catatonia. ¹⁹ With these studies in mind, wherein, stimulation of DLPFC was helpful for negative/catatonic symptoms and TPJ stimulation for hallucinations,^{9, 14} we used a uniform protocol of anode over left DLPFC and cathode left temporo-parietal junction.

In conclusion, as tDCS is rapidly emerging as a safe and tolerable neuromodulatory intervention in children and adolescents for neuropsychiatric disorders, it can be useful, especially, in treating hallucinations during early recovery period of NMS and treatment-resistant catatonia associated with depressive disorder. These findings need to be replicated in randomized controlled studies to determine the efficacy and recommendation for routine clinical practice.