Non-specific noradrenaline reuptake inhibition by high dose selective serotonin reuptake inhibitors, along with catecholamine release from phaeochromocytoma, may lead to a hypertensive paroxysm. This may unmask a clinically silent phaeochromocytoma. Hypertensive paroxysm induced by paroxetine leading to detection of phaeochromocytoma has been reported. The first patient in whom fluoxetine unmasked a phaeochromocytoma is reported.
- selective serotonin reuptake inhibitor
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A 29 year old man was prescribed fluoxetine (selective serotonin reuptake inhibitor) 20 mg/day for depression. In view of his poor response the fluoxetine dose was doubled to 40 mg/day. A few days later he presented with paroxysmal attacks of palpitations, nausea, headache, pallor, perspiration, and headache. His other medication was diazepam. On examination the patient was agitated, apprehensive, and had marked peripheral vasoconstriction. His blood pressure varied between 250/140 and 80/30 mm Hg. There was no postural hypotension. Phaeochromocytoma was considered in view of paroxysmal nature of symptoms and fluctuations of blood pressure. Blood pressure recorded earlier was normal. Twenty four hour excretion of noradrenaline was 10.3 nmol/day (normal range 0.06–0.47), adrenaline 32 nmol/day (normal <0.016), and vanillylmandelic acid 134 μmol/day (normal <30).
Magnetic resonance imaging of the abdomen for a suspected pheochromocytoma revealed a 3 cm diameter mass in the right adrenal gland. After surgical removal of the right adrenal gland, histological examination confirmed the presence of a phaeochromocytoma. The patient has been normotensive since then, and has no symptoms.
Tricyclic antidepressant drugs lead to increased concentrations of noradrenaline due to inhibited presynaptic reuptake of noradrenaline. Although this effect is beneficial, it can lead to haemodynamic abnormalities, particularly when used with monoamine oxidase inhibitors or in a patient with phaeochromocytoma.1 Similar haemodynamic effects are seen when selective serotonin reuptake inhibitors are used along with a monoamine oxidase inhibitor.2
A difference in selectivity has been seen in animal studies between various serotonin reuptake inhibitors, regarding dose dependent inhibition of noradrenaline uptake. In humans, such inhibition in therapeutic dosage has not been shown.3
Activity of cytochrome P-450 (CYP2D6) determines the rate of fluoxetine metabolism; this differs between poor and prolific metaboliser patients.4 Non-specific noradrenaline reuptake inhibition by high dose serotonin reuptake inhibitors, along with catecholamine release from phaeochromocytoma, may explain the haemodynamic abnormalities seen in this patient. Inhibition of serotonin reuptake by platelets may result in increased plasma serotonin concentrations. This in turn leads to higher sensitivity of noradrenaline receptor, thus providing an alternative explanation for paroxysms of haemodynamic abnormalities.5
Paroxetine has been implicated in such adverse effects in a patient with pheochromocytoma.6 There is no report of fluoxetine leading to such effects until now. Clinicians should suspect phaeochromocytoma or drug interactions when hypertension is detected during treatment with selective serotonin reuptake inhibitors.
Phaeochromocytoma or drug interactions should be suspected when hypertension is detected during treatment with fluoxetine.