Reversible hyponatraemia with venlafaxine in a young patient

Abstract

A 28-year-old woman with a depressive episode developed hyponatraemia (126 mmol/l), in the absence of hypovolaemia, oedema, or diuretic use, 2 weeks after starting treatment with the antidepressant venlafaxine. Full blood count, potassium, urea, creatinine, thyroid function test, liver function test, amylase, serum cortisol, and glucose were all normal. A repeat blood test 3 days later revealed a further reduction in the sodium concentration to 123 mmol/l. The patient did not have any signs or symptoms of physical disorder secondary to hyponatraemia on this occasion. Her serum sodium reached normal values 2 weeks after stopping treatment with venlafaxine. Hyponatraemia secondary to venlafaxine has been reported in the older population but not in young people. We therefore believe this is an important finding.

Background

To our knowledge, this is the first reported case of venlafaxine induced hyponatraemia in a young patient. There was no clinical indication of other causes of low sodium values such as diarrhoea, vomiting, nephrotic syndrome, cardiac failure, cirrhosis of the liver, renal failure, hypothyroidism, glucocorticoid insufficiency or Addison disease. We believe venlafaxine caused the reduced sodium concentration. When prescribing antidepressants, physicians/psychiatrists should be alerted to the possibility of venlafaxine associated hyponatraemia, even in younger patients.

Case presentation

On 23 February 2009, a 28-year-old female patient presented to our adult psychiatric unit with a severe depressive episode. She was already being treated with a selective serotonin reuptake inhibitor (SSRI) (citalopram 40 mg), which was prescribed by her general practitioner. As the patient was not responding to citalopram, 37.5 mg of venlafaxine was initiated and citalopram gradually stopped. This dose was increased to 75 mg after a week.

On 4 April 2009, the patient was admitted to our department again after taking 14 tablets of co-codamol with the intention of ending her life. During her routine blood investigations, a serum sodium concentration of 123 mmol/l was noted. The finding of hyponatraemia appears to be unrelated to the overdose of co-codamol for the following reasons:

• There has been no report of hyponatraemia associated with codeine/paracetamol/or its combination

• On the contrary, hypernatraemia has been noted in older patients on paracetamol

• Sodium values continued to drop for 2 weeks after overdose and only returned to normal following discontinuation of venlafaxine

• Hyponatraemia is not a documented side effect of codeine/paracetamol/or its combination in the British National Formulary (2009 edition).

Her detailed history did not identify any risk factors which could account for the low serum sodium values. The patient’s physical examination revealed no abnormalities.

Investigations

• Serum sodium was 123mmol/l

• Serum osmolality was 268 mmol/kg

• Urine osmolality was 257 mmol/kg

• Urine sodium was 57mmol/l

• Serum cortisol, thyroid stimulating hormone (TSH), amylase, urea, and creatinine were all normal.

Differential diagnosis

• Syndrome of inappropriate antidiuretic hormone secretion

• Water overload

• Severe hypothyroidism

• Glucocorticoid insufficiency

Treatment

• Venlafaxine was stopped immediately

• Fluid restriction to 1.5 litres per day

• Regular monitoring of serum sodium concentrations.

Outcome and follow-up

Following treatment, the serum sodium returned to normal values. The patient improved clinically with a full resolution of her depression. The patient’s improvement was a result of the natural course of the illness and the psychological intervention provided on the ward. The patient was discharged after 3 weeks with a psychiatric diagnosis of severe depressive episode without psychotic symptoms. In addition, the patient was also referred for psychological treatment (cognitive behavioural therapy) along with follow-up by home treatment and the community mental health team.

Discussion

Euvolaemic hypo-osmolar hyponatraemia from the syndrome of inappropriate antidiuretic hormone secretion is associated with various systemic factors (for example, increased age, malignancy, pulmonary disease, and central nervous system lesions) and may be medication induced (for example, thiazide diuretics, vincristine, cyclophosphamide, and chlorpropamide).¹ Hyponatraemia secondary to psychotropic medications (for example, SSRIs, trazodone, nefazodone, reboxetine, mirtazepine, amoxapine, maprotiline, bupropion, carbamazepine, phenothiazines, tricyclic antidepressants, and monamine oxidase inhibitors) have been reported in elderly patients.¹ Although less frequently reported than with SSRIs, there have been reports of hyponatraemia with venlafaxine too. This risk may be due to venlafaxine’s SSRI-like properties.

In a retrospective study, Kirby et al found hyponatraemia in 39% of elderly psychiatric patients receiving an SSRI or venlafaxine versus 10% in comparison subjects. In their study, 10 of the 14 patients on venlafaxine developed hyponatremia.² Roxanas et al, in a prospective study, found hyponatraemia in 10 of the 58 patients within a few days of starting venlafaxine.³ Romero also reported hyponatraemia associated with syndrome of inappropriate antidiuretic hormone secretion in an 87-year-old man with depression after starting treatment with citalopram. Sodium values returned to the normal range following discontinuation of citalopram. Subsequently, due to the persistence of depression, treatment with venlafaxine was initiated. Three weeks later, hyponatraemia associated with syndrome of inappropriate antidiuretic hormone secretion was once again found and venlafaxine was discontinued.⁴ Boyd reported 15 cases of venlafaxine associated hyponatraemia to the Adverse Drug Reactions Advisory Committee in Australia.⁵ All of these studies have been completed in the elderly population.

Our findings replicate those of Boyd, Kirby and others, but in young people on venlafaxine. Our study highlights the importance of also evaluating young patients for hyponatraemia secondary to antidepressant treatment.

Learning points

• When prescribing antidepressants for young patients, physicians/psychiatrists should be alerted to the possibility of SSRI or venlafaxine associated hyponatraemia.

• Young patients on venlafaxine should also have their serum sodium values monitored.

• Although it is infrequent, it would still be useful for clinicians to be aware that antidepressants may cause hyponatraemia associated with the syndrome of inappropriate antidiuretic hormone secretion in young as well as elderly patients.