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Case Report: High Plasma Level Tricyclic Antidepressant Therapy in Children: A Case Report and Commentary

Case Report: High Plasma Level Tricyclic Antidepressant Therapy in Children: A Case Report and Commentary


It is well known that some adults with major depression fail to respond to tricyclic antidepressants (TCA) at typical doses and plasma levels, but do respond at higher than standard levels. The literature on high-dose TCA treatment and high plasma level treatment in adults is reviewed, along with the more limited literature in children and adolescents. A case is described of a 5-year-old girl with major depression who did not respond to treatment with nortriptyline until the dose was raised to 200 mg daily (7.2 mg/kg, plasma level = 342 ng/ml). She experienced relatively minor side effects at these levels, and showed clinical deterioration when her plasma level was lowered to 188 ng/ml (160 mg/day, 5.8 mg/kg). Her high-dose and plasma level requirement was supported in an ABABA open clinical trial. High-dose, or high plasma level, treatment with tricyclic antidepressants may be a useful therapeutic option for some severely depressed children after more conventional treatments have failed. The general use of high-dose TCA treatment does not seem warranted or safe, but may be valuable for a selected subgroup of patients. Specific treatment guidelines are offered, including criteria for patient selection and monitoring for mild delirium, neurotoxic changes, seizures, electrocardiographic changes, and cardiovascular effects.
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