Letters to the Editor
Lamotrigine-Induced Neutropenia
Dear Editor:
Lamotrigine’s popularity as a psychotropic continues to rise because of growing evidence for its efficacy and a favourable side effect profile. Although rare, hematological side effects, including neutropenia, have been reported (1).
Case Report
AP is a woman aged 23 years who was hospitalized for treatment of bipolar II disorder, depressed phase. Comorbid diagnoses included polysubstance abuse and eating disorder not otherwise specified.
Treatment with topiramate had been initiated 2 months prior to admission, to which AP had partially adhered.
Topiramate 50 mg at bedtime was initiated on admission (day 1). This was increased to 100 mg at bedtime on day 10. It was decreased to 75 mg on day 15 and further decreased to 50 mg on day 26. Lamotrigine 12.5 mg at bedtime was added on day 15. It was increased to 25 mg on day 19 and further increased to 50 mg on day 26.
A complete blood count (CBC) on day 2 was normal. Neutropenia (1.0 × 109/L) was noted in a random CBC on day 29. Topiramate 50 mg at bedtime and lamotrigine 50 mg were discontinued. The patient’s neutrophil count increased over a 2-week period to 2.0 × 109/L on day 43 and 2.4 × 109/L on day 44.
Rechallenge with lamotrigine 5 mg at bedtime was initiated on day 46. Neutrophils dropped to 1.8 × 109/L on day 48, so lamotrigine was discontinued. Neutrophils rose to 2.2 × 109/L on day 49 and to 2.4 × 109/L on day 50.
Discussion
There appears to be an association between lamotrigine and the development of neutropenia in this patient. Neutropenia appeared first on a random CBC 14 days after the addition of lamotrigine. The neutrophil count normalized 14 days after medication was stopped but dropped following lamotrigine rechallenge. A longer rechallenge period with monitoring might have been warranted. However, there was concern about exposing the patient to possible risk. The patient did not experience any clinical sequelae as a result of this adverse reaction.
Other potential causes were investigated. The Topamax® product monograph reports an incidence of leukopenia of 2.7% with 200 to 400 mg daily and 1.2% with 600 to 1000 mg daily in adults (2). When neutropenia first occurred, this patient was taking topiramate and lamotrigine concurrently. She had been taking low-dosage topiramate for about 2 months prior to admission, without significant hematological events. She was not on topiramate during lamotrigine rechallenge. During her hospitalization, AP lost 7 kg. There was concern that her poor nutritional status might have contributed to neutropenia. Eating disorders have been associated with hematological complications: anorexia nervosa has been linked to bone marrow hypoplasia and resultant hematological side effects, including neutropenia (3). During lamotrigine rechallenge, AP’s nutritional status was reasonable.
The exact pathophysiology of lamotrigine-induced neutropenia is unknown (4). A literature review produced several reports of lamotrigine-induced neutropenia that reversed upon drug discontinuation (5–7). There is limited information on rechallenge (8). In this patient, rechallenge with a minimal dosage again lowered neutrophil counts. This case further documents lamotrigine-induced neutropenia in a patient with slow up-titration, as well as the outcome of rechallenge. It highlights the need for careful monitoring of blood work.
References
1. GlaxoSmithKline Inc. Lamictal® (lamotrigine) product monograph. Missassauga (ON): GlaxoSmithKline Inc; 2001.
2. Janssen-Ortho Inc. Topamax,® (topiramate) product monograph. Toronoto ON): Janssen-Ortho Inc; 2002.
3. Devugst O, Lambert J. Rodhain J, Lefebvre C, Coche E. Hematological changes and infectious complication in anorexia nervosa. Q J Med 1993;86:791–9.
4. Fadul CE, Meyer LP, Jobst BC, Cornell CJ, Lewis LD. Agranulocytosis associated with lamotrigine in a patient with a low grade glioma. Epilepsia 2002;43:199–200.
5. De Camargo O, Bode H. Agranulocytosis associated with lamotrigine. BMJ 1999;318:11.
6. Nicholson RJ, Kelly KP, Grand IS. Leukopenia associated with lamotrigine. BMJ 1995;310:504.
7. Normann C, Hummel B, Scharer LO, Horn M, Grunze H, Walden J. Lamotrigine as an adjunct to paroxetine in acute depression. J Clin Psychiatry 2002;63:337–44.
8. Lambert O, Veyrac G, Armand C, Bourlon S, Bourin M, Jolliet P. Lamotrigine-induced neutropenia following two attempts to increase dosage above 50mg/day with recovery between episodes. Adverse Drug Reacti Toxicol Rev 2002;1:57–9.
Kellie LeDrew, MD, FRCPC
Leslie Phillips, BSc (Pharm), PharmD
Maureen Hogan, BSc, MD
Amanda MacCallum, BSc (Pharm)
Kingston, Ontario
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