Abstract
Lamotrigine-induced mania in adolescents
The treatment of bipolar depression is adolescents is not well researched and pharmacological strategies are supported only by case series data [1–5]. Lamotrigine is increasingly recognized as efficacious and is well tolerated as a mood stabilizer in adults with bipolar disorder [6], particularly in the depressive phase [7]. The small number of studies in youth suggest that, as in adults, adolescents with bipolar disorder appear to respond to treatment with lamotrigine, with decreases in depression, mania, and aggression [4].
Lamotrigine has recently been fully funded in New Zealand for use in bipolar disorder although its use in children and adolescents is ‘off label’. We report two cases of lamotrigine-induced mania in the first two (and only) young people we have treated with lamotrigine for bipolar depression.
Patient A was a 17-year-old school girl with a 2 year history of bipolar 1 disorder characterized by alternating mixed mood states and depressive episodes with no previous mania. She also had a previous history of comorbid substance abuse with alcohol, marijuana and stimulant drugs (methylphenidate) but for the last 6 months admitted to only abusing alcohol, which was confirmed by urine tests. She was managed on lithium and quetiapine. Following a 4 month period of pervasive low mood with significant impairment in functioning, she was commenced on a trial of lamotrigine. At 25 mg daily she described elevated mood, racing thoughts and agitated behaviour, increased sexual interest and grandiose ideation but no psychosis. On withdrawal of the lamotrigine her symptoms resolved spontaneously within 10 days.
Patient B was also a 17-year-old girl with a 3 year history of bipolar 1 disorder that presented with mania. Over the subsequent years her functioning both academically and socially was significantly impaired with long episodes of depression. She had previously had a mixed mood state induced by a selective serotonin re-uptake inhibitor and was on therapeutic doses of lithium and quetiapine. There was no history of substance abuse. Lamotrigine was commenced after a 4 month period of increasing low mood and marked suicidality and was titrated slowly over 8 weeks to 100 mg daily as recommended in this age group [4]. She began to notice an effect on mood at the 50 mg day−1 level and became more motivated and had energy and interest in previously neglected activities. After being on lamotrigine (100 mg daily) for 2 weeks, her energy levels and drive became more marked and by 4 weeks she became manic and required hospitalization.
A literature search of journals and adverse report data bases for mania induction by lamotrigine yielded few cases [5, 8–10], with only one in childhood [5]. We report these two cases to alert colleagues to this serious effect, which may be a feature of lamotrigine use in younger patients with bipolar disorder.
Trichotillomania in acute Sydenham's chorea
Trichotillomania is defined in DSM-IV as recurrent pulling out of one's own hair that results in noticeable alopecia. Many patients describe an urge or great anxiety before pulling out hair followed by relief after completion. Thus trichotillomania and obsessive–compulsive disorder (OCD) may share similar phenomenology and, probably, therapeutic response. It has been proposed that trichotillomania should be included under an obsessive–compulsive spectrum [1].
OCD is frequently seen in Sydenham's chorea, a movement disorder resulting from an autoimmune process triggered by the nasopharyngeal streptococcal infection in children [2]. There is only one case report in the literature describing a child who presented hair pulling concomitant to Sydenham's chorea [3]. In that case trichotillomania waxed and waned according to the neurological symptoms. Herein we report an additional case in which a 13-year-old girl presented trichotillomania in association with acute Sydenham's chorea.
This girl was referred to the Movement Disorders Clinic of the Federal University of Minas Gerais (UFMG) due to the presence of involuntary, rapid and non-rhythmic movements started on the right side of her body 2 weeks previously. On the following days these involuntary movements spread to her entire body, interfering in several activities of her daily living. Her parents also noticed behavioural changes paralleling motor symptoms, including irritability, emotional lability and hyperactivity. Her previous medical history was unremarkable except for the report of pharyngitis 1 month before the onset of her illness.
On examination the patient exhibited moderate choreic movements and reduced muscle tone in all limbs. Her speech was dysarthric. Laboratory work-up indicated increased serum titres of anti-streptolisin O (556 UI mL−1; reference value <200 UI mL−1) and erythrocyte sedimentation rate (35 mm h−1; reference value <20 mm h−1). Echocardiogram demonstrated mild insufficiency of mitral and tricuspid valves. Thus the diagnosis of rheumatic fever and Sydenham's chorea was established.
She was started on penicillin G benzathine 1.2×106 UI every 3 weeks and valproic acid 250 mg twice a day. One week after the onset of treatment she started complaining about an irresistible desire to pull out her scalp hair, which produced a small area of alopecia. She scored 24 (out of 28) on the Massachusetts General Hospital Hair-pulling Scale. Her choreic movements were unaltered. Then the dose of valproic acid dose was titrated to 250 mg three times a day. Within 4 weeks there was a significant improvement in motor symptoms and the hair-pulling behaviour had disappeared. On follow up the chorea had abated completely in 2 months and the patient returned to her premorbid level of functioning.
In the present case trichotillomania appeared in a patient with acute Sydenham's chorea. It is unlikely that this behaviour was caused by valproic acid because the up-titration of this drug from 500 mg to 750 mg day−1 was followed by clinical improvement. Thus we hypothesize that trichotillomania resulted from the immune-mediated basal ganglia dysfunction characteristic of Sydenham's chorea.
There is still much controversy regarding the neurobiology of trichotillomania. Based on its possible relationship to obsessive–compulsive spectrum disorders, it has been proposed that basal ganglia abnormalities and/or frontostriatal dysfunction are involved in its pathogenesis [4, 5]. Thus the present case report corroborates this view.