QJM Advance Access originally published online on December 15, 2006
QJM 2007 100(1):61-62; doi:10.1093/qjmed/hcl134
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Reboxetine treatment and pseudopheochromocytoma
Sir,A 47-year-old man with familial Mediterranean fever treated with colchicine, and chronic obstructive pulmonary disease (with no regular treatment), developed major depression. Reboxetine (Edronax, 8 mg/day), fluoxetine (Prozac, 20 mg/day), and clonazepam (2 mg/day) were started. After a year, he developed episodic dizziness and syncope, and was admitted following his fifth syncope. He denied palpitations or chest pain, and had no headache, convulsions or preceding aura. Examination was unremarkable, and basic laboratory tests, thyroid function tests, chest X-ray, ECG, echocardiography, EEG, head CT, and carotid duplex were all normal. 24-h Holter monitoring revealed asymptomatic runs of sinus tachycardia (118/min) over up to 4 min. The patient was discharged on metoprolol 50 mg qd but re-admitted after further similar spells. Recumbent blood pressure was 148/85 mmHg, with a marked drop to 100/50 after assuming the upright posture. At the same time, heart rate increased from 84 to 114 bpm. Pheochromocytoma was strongly suspected, and urinary collections for catecholamines and their metabolites were performed and examined by HPLC. Very high levels were revealed (Table 1). To rule out drug-induced catecholamine elevations (considered a remote possibility) reboxetine and fluoxetine were discontinued. Measurements of urinary catecholamines and metabolites were repeated 3 and 5 months later. A significant drop in urinary catecholamine levels was demonstrated. Abdominal CT was normal. Five months after drug withdrawal, epinephrine and norepinephrine (NE) levels demonstrated further decrease to normal values (Table 1). The patient remained free of symptoms at 2 years, and repeated urinary catecholamines were again normal. Rechallenge with the drug was deemed unethical.
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Sympathetic overactivity and abnormal urinary catecholamine assays due to drug treatment are well documented. Tricyclic antidepressants, varied sympatho-mimetic drugs or the combination of monoamine oxidase (MAO) inhibitors and tyramine-containing foods can all increase the release of catecholamines and mimic pheochromocytoma.1,2 However, we are not aware that increased adrenergic activity associated with fluoxetine and reboxetine has been previously reported. Reboxetine is the more likely culprit.2 Despite many patient-years of SSRI drugs usage, we were able to find reports of only two cases of pheochromocytoma unearthed by SSRIs: fluoxetine and paroxetine were involved.3,4 Reboxetine represents a new class of antidepressant agents with specificity for the noradrenergic system. It acts by binding to the NE transporter and blocking reuptake of extracellular NE back into terminals,5 and thus could cause the substantial increase in catecholamines found in our patient, which dropped to normal upon drug withdrawal. With the expected increasing use of reboxetine, these clinical and biochemical effects may be encountered in some patients and need to be recognized.
Kaplan Medical Center
Rehovot
Israel
email: amiMD{at}clalit.org.il
References
1. Kudva YC, Sawka AM, Young W. (2003) The laboratory diagnosis of adrenal pheochromocytoma: the Mayo clinic experience. J Clin Endocrinol Metab 88 4533–9.
2. Eisenhofer G, Goldstein DS, Walther MM, Friberg P. (2003) Biochemical Diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J Clin Endocrinol Metab 88 2656–66.
3. Seelen MA, de Meijer PH, Meinders AE. (1997) Serotonin reuptake inhibitor unmasks a pheochromocytoma. Ann Intern Med 126 33.
4. Kashyap AS. (2000) Phaeochromocytoma unearthed by fluooxetine. Postgrad Med J 76 303.
5. Hajos M, Fleishaker HM, Filipiak-Reisner JK, Brown MT, Wong EH. (2004) The selective norepinephrine reuptake inhibitor antidepressant reboxetine: pharmacological and clinical profile. CNS Drug Rev 10 23–44.[Web of Science][Medline]
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