Precautions in prescribing serotonin reuptake inhibitors

Dear Editor,

There are a considerable number of psychotropic drugs today that can cause endocrinological and metabolic changes which may affect both treatment adherence and the patient's quality of life and health status. Thus hyperprolactinaemia secondary to antipsychotics¹ — with its effects on gonadal function and bone metabolism —, or therapy with lithium and other antidepressants, with their effects on the thyroid function are just a few examples of this significant issue

Fluoxetine is a powerful selective serotonin reuptake inhibitor (SSRI) which is widely prescribed and indicated in the treatment of episodes of major depression, obsessive-compulsive disorder (OCD), and bulimia nerviosa.² The syndrome of inappropriate secretion of ADH (SIADH) consists of the secretion maintained by ADH failing to have its usual stimuli, in particular hypovolaemia and hyperosmolarity, and is characterised by the presence of hypoosmolar hyponatremia, urine sodium (NaU) above 40 mmol/l and urine osmolarity (OsmU) above 100 mOsm/kg, in absence of the effective reduction of volaemia (heart failure, ascities, hypovolemia,...), once thyroid and suprarrenal failure have been ruled out.³

Tumours, infections and very exceptionally drugs⁴ are the most common causes. Antidepressants and in particular the SSRI have been frequently involved. Although not totally clarified, their physiopathological mechanism may depend on an increased secretion of ADH due to the stimulus of serotoninergic receptors and alpha-adrenergic receptors by the serotonin and noradrenaline.⁵

Pedrós et al.⁶ reviewed 44 spontaneous reports of hyponatraemia and/or SIADH suspected of having been caused by SSRI between 1983 and 2003. Of these, 11 were attributed to fluoxetine. As a result, we present the case of a woman who developed hyponatraemia due to the use of this drug.

A woman aged 76 with a history of high blood pressure, Sjögren's syndrome and osteoporosis. She had been treated with 16 mg/day candesartan and 20 mg/day fluoxetine for the previous 4 months. She presented due to instability when walking, dizziness and mental torpidity of one month onset. Physical examination revealed the absence of oedema and signs of dehydration. Analysis highlighted a plasma NA of 125 mmol/l, plasma Osm 266 mOsm/l (vn: 280–300 mOsm/l), NaU 47 mmol/l and OsmU233 mOsm/l. Cortisol and thyrotophin (TSH) levels were normal.

On suspected SIADH secondary to fluoxetine, the drug was suspended and treatment was initiated with hypertonic saline solution and water deprivation. Clinical and analytical evolution was favourable, with normalisation of the natraemia.

According to its specification sheet¹ SIADH by fluoxetine is a serious and rare adverse effect (≥1/10,000 to <1/1000). Both Pedrós and Gandhi et al.⁷ found there to be a higher risk of hyponatraemia due to SSRI in women over 65 years of age, in concomitant treatment with diuretics and a history of chronic kidney disease or heart failure. One cohort study of the British population⁸ demonstrated a significant increase in the risk of hyponataemia with citalopram, fluoxetine and escitalopram compared with sertraline and paroxetine. The latter was found to be more frequently implicated in the Pedrós study.

To conclude, we believe that caution should be taken when prescribing SSRIs, especially in women over 65 years of age, where there is concomitant use of diuretics or a history of kidney or health failure. In these cases natraemia should be monitored and clinical follow-up should be performed at least in the first three months of treatment.