| | Clonazepam augmentation therapy in a male at early adolescence with rapid cycling bipolar disorderTo the Editor:
Bipolar disorder in adolescent children is not rare, and its lifetime prevalence has been reported to be about 1% [1]. Bipolar disorder in adolescent children is clinically characterized by a high percentage of rapid cyclers and refractory conditions compared with adults [2]. Recently, attention has been paid to the mood-stabilizing action of clonazepam, an antiepileptic. The effects of monotherapy with clonazepam as a mood stabilizer have been shown by previous controlled double-blind trials [3]. In addition, clonazepam augmentation therapy by its combination with conventional mood stabilizers has been reported to have some effects on bipolar in adults [4]. However, to our knowledge, there have been no reports on the effects of clonazepam augmentation therapy on bipolar disorder in children.
We describe an adolescent male with rapid cycling bipolar disorder who did not respond to conventional mood stabilizers but improved after their combination with clonazepam.
1. Case Report  The patient was a 14-year-old male without remarkable family history, who had a normal childhood development. He was gentle-natured, studied hard and had good grades. At the age of 14 years, hypomanic states mainly characterized by hyperthymia and hyperactivity alternated with depressive states mainly characterized by stupor in cycles of several days–1 week for about 3 months. At the age of 14 years and 3 months, a major depressive episode according to the DSM-IV criteria [5] persisted for about 2 weeks, which rapidly shifted to a severe manic state, and he was admitted to our department. On admission, in addition to logorrhea, hyperactivity, flight of ideas, hyperbulia and grandiosity, psychotic symptoms (mainly auditory hallucination) were observed. According to the DSM-IV criteria, a diagnosis of bipolar disorder, severe, with psychotic features, rapid-cycling specifier was made. The clinical course after admission is shown in Fig. 1. The manic state was assessed by the total score in the first 7 items in Petterson’s Rating Scale [6]. The depressive state was assessed by the Hamilton Rating Scale for Depression (HAM-D) [7]. After admission, a severe manic state continued for about 1 month, followed by alternation between depressive phases characterized by stupor and severe manic phases accompanied by auditory hallucination in 10-day cycles. The transfer to each phase was rapid. Monotherapy with mood stabilizers and their combination therapy were performed with changes in their doses to optimum doses under monitoring of serum concentrations (as shown in Fig. 1). First, carbamazepine 400 mg/day (serum level, 9.3 μg/mL) was administered alone for about 1 month, but no effects were observed. Next, valproate 800 mg/day (serum level, 73 μg/mL) was administered in combination with carbamazepine for about 1 month without any noticeable response. Subsequent monotherapy with valproate 1000 mg/day (serum level, 113 μg/mL) for about 1.5 months also had no effects. Then, lithium 600–1,000 mg (serum level, 0.6–0.9 mEq/L) administered in combination with valproate was not effective. However, after clonazepam was added to these mood stabilizers and its dose was increased to 11 mg/day (serum level, 50 μg/L), both manic and depressive phases subsided, resulting in complete remission. Subsequently, follow up was performed for more than 1 year under administration of this drug combination without changes in the dose of each drug, but relapse was not observed. No adverse effects of clonazepam such as ataxia or disinhibition were noted [8]. For marked excitement in manic phases, antipsychotics such as levomepromazine and zotepine were administered when necessary. 2. Discussion In this patient, rapid cycling bipolar disorder developed at the age of 14 years. According to the treatment guidelines of bipolar disorder proposed by James and Javaloyes [9], various monotherapies and combination therapies with mood stabilizers (carbamazepine, valproate and lithium) were performed, but no clinical effects were observed. Of children with bipolar disorder at adolescence or preadolescence, about 80% have been reported to show rapid cyclers and have refractory conditions compared with adults [2]. In children with an acute manic phase, the reported rates of the response to mood stabilizers vary but are relatively low: 30–50% for valproate [10], [11], 30–70% for lithium [11], [12], and about 40% for carbamazepine [11], while the effectiveness of the combination therapy with mood stabilizers has not been confirmed. In this patient, augmentation therapy by addition of clonazepam to mood stabilizers was effective, and complete remission was rapidly achieved. In adult patients, clonazepam has been reported to have antidepressive effects [13] and antimanic effects [8], and decrease the frequency of each manic or depressive phase in bipolar disorder [4]. The effectiveness of augmentation therapy by adding clonazepam to conventional mood stabilizers has also been reported in those patients [14]. However, there have been no studies on the effects of clonazepam augmentation therapy in children with bipolar disorder, or studies that adequately evaluated its effects in bipolar rapid cyclers. This is the first report on the effectiveness of clonazepam augmentation therapy in adolescent children with rapid cycling bipolar disorder and may provide useful findings. Further controlled studies need to be conducted to determine if clonazepam is effective in adolescents with rapid cycling bipolar disorder, whether receiving monotherapy or adjunctive therapy with conventional mood stabilizers. References [1].
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Department of Neuropsychiatry, Fukui Medical University, Fukui 910–1193, Japan PII: S0163-8343(02)00250-5 doi:10.1016/S0163-8343(02)00250-5 © 2003 Elsevier Science Inc. All rights reserved. | |
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