Combined Use of Electroconvulsive Therapy and Amantadine in Adolescent Catatonia Precipitated by Cyber-Bullying

To the Editor:

C atatonia is a unique motor dysregulation syndrome characterized by identifiable signs such as immobility, sometimes alternating with excessive motor activity, that is apparently purposeless and not influenced by external stimuli, extreme negativism or muteness, peculiarities of voluntary movement, echolalia, or echopraxia (Fink and Taylor 2009). Catatonia accompanies a number of general medical and neurologic conditions (Dhossche and Wachtel 2010), with acute or insidious onset. In its most severe forms, catatonia may become life threatening, especially when aggravated by autonomic dysfunction and fever. Although previously considered to be rare in children and adolescents (Cohen et al. 1999), recent reports suggest that the prevalence of catatonic symptoms in these age groups is in fact similar to that reported in adults (Ghaziuddin et al. 2012). Overwhelming stress and trauma may trigger catatonia in children and adolescents (Dhossche et al. 2012). Benzodiazepines and electroconvulsive therapy (ECT) are considered first-line treatments (Weiss et al. 2012); however, the literature offers little guidance in cases that do not respond or that respond slowly to a course of these primary treatments. We present an adolescent case with close temporal relationship between onset of catatonia and cyber-bullying, a severe but common stressor nowadays for many adolescents, which resolved with daily ECT and adjunctive amantadine. We did not find any prior published accounts of these features in adolescents.

Case Report

A 14-year-old Caucasian girl was admitted to our hospital because of a rapid change in her mental status following significant stress and emotional turmoil from cyber-bullying by a male schoolmate. Pre-morbidly, the girl had been an excellent, A-grade, high school student who had excelled in sports and music. At 5 years of age, she had manifested symptoms of separation anxiety, which resolved without any therapeutic intervention. The family history was negative for psychiatric diagnoses and treatment. The parents had experienced a serious traumatic event when they lost her first son a few years before our patient was born.

The first symptoms of her current illness emerged 2 weeks before hosptal admission. Her teachers reported that she had increased energy, higher distractibility, and restlessness. In addition, her parents noted that she was often tearful, showed a decreased need for sleep, and demanded to sleep in her parents' bedroom. A few days later, her behavior became disorganzed. She wore two or more pieces of underwear, also appeared confused in a relay event and ran out of the stadium. She started to talk about death and to take photographs of tombstones, placing candles everywhere at home and drawing strange pictograms. Her parents took her to a local child psychiatrist who diagnosed acute polymorphic psychotic disorder, prescribed 0.5 mg risperidone p.o., and recommended inpatient treatment at the Department of Child and Adolescent Psychiatry.

During the initial psychiatric interview at our facility, the girl appeared confused, anxious, and tearful. She said that she was pregnant and that the baby was her deceased brother. She reported hearing vague and strange noises. She also complained that she had watched several television programs about herself.

The results of laboratory tests (blood count, biochemical analyses, magnetic resonance imaging [MRI] and electroencephalogram [EEG]) were normal. A pregnancy test and a screen for illegal substances were negative. Using a semistructured interview, the girl was diagnosed with a brief psychotic disorder and we continued with risperidone (1 mg p.o.) and clonazepam in solution (1 mg p.o. per day). Two days, later the girl appeared hyperactive, performed acrobatic exercises on the ward, and was confused. Risperidone was gradually increased to 2 mg per day. Her sleep was poor and she required constant supervision. On the 5th day, she stated that she was on the beach of “Helios Island” and that “everything is the dream, I am in the dream.” At times, she walked nude on the ward, and was found kneeling and standing without being able to explain her behavior. The girl was diagnosed with oneiroid catatonia. Clonazepam was increased to 2.5 mg per day (lorazepam is not approved in the Czech Republic). Treatment with risperidone was switched to 5 mg of olanzapine p.o., which has been used previously in patients with catatonia treated at our department (Dudova and Hrdlicka 2008). Olanzapine was gradualy increased to a daily dose of 15 mg during the next 2 days. Two days later the girl developed frank catatonia characterized by agitation, increased gesturing of the hands and the fingers, alternating with mutism, immobility, posturing, refusal to eat and drink, and incontinence. Typical waxy flexibility was registered during physical examination. She had to be restrained in bed because of agitation and aggression. Her vital functions were monitored. Olanzapine and clonazepam were withdrawn and ECT was initiated after obtaining written consent from her parents.

After manual ventilation, bitemporal electrode placement ECT with brief pulse currents was applied using a The Thymatron^® System IV, Class 1, Type BF (Somatics, INC). ECT was started at 15% of maximum energy as recommended for Thymatron System IV given the patient's age (pulse width 0.5 ms, charge 76.0 mC, stimulus duration 4.2 seconds, frequency 20 Hz). Seizure durations of 25–35 seconds and 92–105 seconds were recorded during the first two sessions. However, seizure duration on the 3rd day was inadequate, and, therefore, the energy was increased to 20% (pulse width 0.5 ms, charge 100.3 mC, stimulus duration 5.6 seconds, frequency 20Hz) resulting in a seizure duration of 15–20 seconds. There were no lucid intervals for the patient after the first five sessions. Energy was increased to 30% (pulse width 0.5 ms, charge 150.8 mC, stimulus duration 5.6 seconds, frequency 30 Hz) for the sixth ECT; however, the stimulus had to be repeated because of almost no response after the first one. There was a lucid interval following ECT that lasted only a few minutes and the patient quickly relapsed into stupor, mutism, immobilty, and negativism. Mild subfebrility was noted (37.1–376°C). Given the lack of improvement, i.v. adjunct amantadine treatment (250 mg twice daily) was initiated. The first infusion was applied after ECT, the second one in the evening. The next day, the first dose of amantadine was applied in the morning ∼90 minutes before ECT, the second dose was applied at 6 p.m. This scheme of amantadine administration was kept for the rest of the treatment trial. Seizure duration was 100 seconds following the seventh ECT with 30% of energy. There was a transient lucid period, and, overall, the patient's negativism decreased and oral intake increased. Subfebrility was noted (37.4°C). The patient still had to be restrained in bed, although she had brief intervals during which she was able to walk with assistance. Energy output in ECT sessions 8–12 was kept at 50% (pulse width 0.5 ms, charge 255.0 mC, stimulus duration 7 seconds, frequency 40 Hz) resulting in seizures varying from 35 to 60 seconds. The patient continued to improve, showed more eye contact, and was able to reply to simple questions during the lucid intervals following ECT. Oral intake was more frequent. She also started more intense physiotherapy. However, during some evenings, she showed aggression and agitation. From the tenth ECT onwards (5th day of amantadine), restraining the patient in bed was necessary only when infusions were applied. She walked freely on the ward and oral intake was regular. Impairment of speech was still present, with incoherence, frequent verbigerations, perseverations, and echolalia.

After the patient's last ECT, treatment with olanzapine p.o. (5 mg in the evening and later every other day) and solution of clonazepam p.o. (2.5 mg divided into three doses) was re-intitiated while amantadine was gradually withdrawn. During the following week, the patient communicated in a somewhat infantile way using diminutives, was moderately anxious, and had some speech delay. Impairment of short-term memory was observed. Hallucinations and delusions disappeared during the 2nd week of pharmacological treatment. The girl was still inhibited, anxious,and inactive. With ongoing treatment, her speech continuously improved, her anxiety decreased, and she expressed a wider range of emotions. Gradually, she started to read books and attend school at the hospital. She was discharged from the inpatient psychiatric unit 6 weeks after her last ECT on olanzapine (10 mg) monotherapy. Because of marked weight increase (11 kg) during the first year of outpatient treatment, the olanzapine was replaced with aripiprazole (10 mg).There have been no relapses during the 24 month follow-up, and she successfully resumed her high school studies.

Discussion

We report a case of a 14-year-old girl with severe catatonia precipitated by emotional turmoil, who was successfully treated with intensive ECT and the N-methyl-D-aspartate (NMDA) antagonist amantadine. The case is a stark reminder of the traumatic impact of cyber-bullying as a possible precipitant of catatonia in our patient. Traumatic events in childhood and adolescence represent risk factors for the later development of affective and psychotic disorders (Kelleher et al. 2008; Arseneault et al. 2011). The difficulty of escaping from it is a prominent characteristic of cyber-bullying, increasing its traumatic impact (Sourander et al. 2010). At follow-up, our patient claimed amnesia for the period of hospitalization but recalled vividly her profound feelings of despair, shame, and defenselessness while being cyber-bullied. In an epidemiologic study of 1098 adolescents, those who experienced bullying three or more times a month were 3.43 times as likely to report increasing psychotic experiences (Mackie et al. 2012). Our case extends findings that adolescent bullying increases the risk for psychotic experiences by linking cyber-bullying, an intrusive form of bullying, to onset of catatonia. This supports the concept that severe traumatic events are risk factors for catatonia and that catatonia may represent an evolutionary-based fear response (Moskowitz 2004; Dhossche et al. 2012).

Onset of psychosis in our patient was rapid, and was preceded by anxiety, restlessness, hyperactivity, insomnia, disorganized behavior, and confusion following significant stress and fear because of cyber-bullying. The first manifestation of psychosis meets the criteria for delirious mania (Fink and Taylor, 2003). Delirious mania is now subsumed under acute psychosis in International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10). Bonner and Kent (1936) view catatonia and delirious mania as overlapping syndromes. However, brief polymorphic psychosis in ICD-10 lacks a specifier for catatonia, unlike brief psychotic disorder in American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) (Bauer et al. 2012). Catatonic features are usually present in delirous mania; however, they are frequently overlooked and, erroneously, antipsychotics are selected as first choice treatment (Fink and Taylor 2003). We cannot exclude the possibility that risperidone led to a worsening of the clinical state in our patient. The risk of worsening catatonia appears greater with antipsychotics with higher dopamine D2 blockade and the potential to cause extrapyramidal side effects (Lee 2010), which is the case with risperidone. Neuroleptic malignant syndrome (NMS), considered by some to be the most severe drug-induced form of catatonia (Fink and Taylor 2006), has been reported more frequently during treatment with risperidone than with other atypical antipsychotics (Trollor et al. 2009). We diagnosed catatonia based on the patient's dream-like, oneiroid state, accompanied with perseverations and some of the typical catatonic symptoms such as stereotypic movements and negativism. Olanzapine has been reported to be effective in the treatment of catatonic schizophrenia, both in children (Ceylan et al. 2010) and adolescents (DelBello et al. 2000; Dudova and Hrdlicka 2008). However, no improvement was observed in our patient. As lorazepam is not available for clinical use in this country, we prescribed a 2.5 mg dose of clonazepam p.o. as an adjunct to olanzapine. Resolution of catatonic symptoms has been reported previously in adolescents receiving a 0.05 mg/kg daily dose of clonazepam (Askenazy et al. 2010). However, after starting olanzapine, our patient developed full-blown catatonic syndrome. A worsening of catatonia and precipitation of NMS in association with olanzapine has also been described anecdotally (Lewis et al. 2009). Severe catatonic syndrome with excitement, refusal of oral intake, and combativeness requiring permanent restraint in bed led us to withdraw the medication and start with daily bilateral ECT.

ECT is considered a highly effective, rapidly acting and safe treatment for catatonia in children (Esmaili and Malek 2007; Wachtel et al. 2010) and adolescents (Consoli et al. 2010). However, five daily ECT sessions with a bitemporal application did not improve our patient. This could be accounted for by the short treatment course and short duration of seizures (ECT3-ECT5), as severe catatonia usually requires intensive and longer treatment courses of ECT than five sessions (Fink and Taylor 2009).

In an attempt to speed up recovery, we chose to add the NMDA antagonist amantadine based on reported positive effects in previous cases of refractory catatonia (Northoff et al. 1997; Carroll et al. 2007). The response time to amantadine in catatonia ranged from 1 to 7 days (Carroll et al. 2007). Our patient started with amantadine intravenously from the 5th ECT session, with substantial improvement registered after the 8th ECT treatment and with reduction of catatonia after the 12th ECT session.

Improvement and remission in our case may be the result of continuing ECT regardless of adjunct therapy with amantadine, especially considering the longer duration of seizures (ECT6-8) after increasing the energy. Some authors consider a typical ECT course of 5–10 ECT treatments, used for depressive disorders, inadequate for catatonia and recommend 10–20 bilateral ECT treatments, with the option of daily applications or double stimulations (Fink and Taylor 2009). Therefore, it remains unclear if ECT and amantadine had additive or synergistic effects in this case, similar to the effect of ketamine, another NMDA antagonist (Kranaster et al. 2012). As there were residual psychotic symptoms after the motor symptoms resolved, we re-started treatment with olanzapine in our patient. This treatment should be monitored closely because of the risk of recurrence of catatonia. Currently, the patient has been stabilized on aripiprazole, which has been reported elsewhere to be effective in adolescent catatonia (Strawn and Delgado 2007).

Early recognition of catatonia in various acute psychotic states is crucial for proper treatment selection, that is, benzodiazepines and ECT. For treatment of residual psychotic symptoms, second generation antipsychotics with low D2 blockade (quetiapine, olanzapine) or with D2 partial agonism (aripiprazole) should be preferred (Carroll et al. 2010). Augmenting ECT with amantadine warrants further study in order to find the optimal treatment of adolescent catatonia. The role of cyber-bullying as a precipitant of catatonia and psychosis also requires further research attention.