Reactions 1073 - 15 Oct 2005

★ SClomipramine

First report of type III hyperlipoproteinaemia: casereport

A 48-year-old man developed type III hyperlipoproteinaemiaduring long-term treatment with clomipramine for majordepressive disorder.

Approximately 5 years after starting treatment withclomipramine 75 mg/day, the man was found to have’moderate’ elevations in his lipid levels. However, when thedosage of clomipramine was increased to 150 mg/day, hedeveloped severe dyslipidaemia [time from dosage increase toreaction onset not clearly stated]. Laboratory investigationsrevealed: triglyceride level 637.2 mg/dL; total cholesterol level694.9 mg/dL; HDL-cholesterol level 81.1 mg/dL; totalcholesterol/HDL-cholesterol ratio 8.6.

When clomipramine was discontinued, laboratoryinvestigations showed a marked improvement after 11 days:triglyceride level 210.6 mg/dL, total cholesterol level338.2 mg/dL, HDL-cholesterol level 51.0 mg/dL, LDL-cholesterol level 245.6 mg/dL, and total cholesterol/HDL-cholesterol ratio 6.6. However, the man’s depressivesymptoms recurred within weeks and clomipramine wasrestarted, leading to severe dyslipidaemia once again.

After the man had been receiving clomipramine forapproximately 20 years, he was referred for severedyslipidaemia; physical examination showed palmarxanthomas, characteristic of type III hyperlipoproteinaemia.He reported that he had first noticed orange discolouration ofhis palmar creases 4 years after starting clomipramine.Apolipoprotein-E2 homozygosity was confirmed by genetictesting.

Since previous treatment with lovastatin had beenunsuccessful, the man received fenofibrate, but his mooddeteriorated and he experienced an increased frequency ofsuicidal ideation. Although it was unclear whether this wascaused by fenofibrate, the drug was discontinued. He thenreceived atorvastatin, and his lipid levels improved:triglyceride level 460.2 mg/dL, total cholesterol level517.4 mg/dL, HDL-cholesterol level 57.9 mg/L, and totalcholesterol/HDL-cholesterol ratio 8.9. He experienceddepressed mood during atorvastatin therapy, and the drug wasdiscontinued. He started treatment with ezetimibe. [Patientoutcome not stated.]

Author comment: "We suggest that the use of tricyclicantidepressants may induce dysbetalipoproteinemia in[apolipoprotein-E2] homozygotes."Holmes DT, et al. Dysbetalipoproteinemia and clomipramine. American Journal ofPsychiatry 162: 1384-1385, No. 7, Jul 2005 - Canada 801018417

» Editorial comment: A search of AdisBase and Medline didnot reveal any previous case reports oftype III hyperlipoproteinaemia associated with clomipramine.The WHO Adverse Drug Reactions database contained10 reports of hyperlipaemia and no reports ofhyperproteinaemia associated with clomipramine.

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Reactions 15 Oct 2005 No. 10730114-9954/10/1073-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved