Mirtazapine-induced massive dyslipidaemia in an elderly woman

To the Editor

Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), primarily acts via alpha 2 receptor antagonism, but also blocks serotonin and histamine receptors (Stahl, 2008). While weight gain is a commonly regarded side effect of mirtazapine, its potential to cause dyslipidaemia, a well-established risk factor for cardiovascular disease, is less commonly reported. This seems in spite of its similar pharmacological action to second-generation (atypical) antipsychotics, whose propensity for causing the ‘metabolic syndrome’ is well characterized.

We report the case of a 76-year-old woman with moderately severe Alzheimer’s disease, who presented with a 6-month history of worsening depression and persecutory ideation, and with the recent development of suicidal ideation and aggression.

Psychotropic medications on admission included olanzapine, memantine and desvenlafaxine, none of which had demonstrated benefit in this patient for their prescribed indications. The patient’s co-morbid diagnoses included insulin-dependent diabetes, seronegative arthritis, hypertension, atrial fibrillation and osteoporosis. Other medications included sotalol, digoxin, methotrexate and prednisolone, none of which had been recently altered. The patient’s weight on admission was 68.0 kg, and baseline serum cholesterol and triglyceride levels were 6.2 mmol/L and 7.8 mmol/L, respectively.

Olanzapine, desvenlafaxine and memantine were withdrawn following admission, and on day 14 of the admission mirtazapine was commenced. After 3 weeks of mirtazapine therapy, fasting cholesterol and triglyceride levels had surged to 8.0 mmol/L and 27.1 mmol/L, respectively. Pravastatin, fenofibrate and fish oil were commenced to manage the dyslipidaemia.

Subsequent review of the literature revealed a small, randomised, controlled trial of healthy subjects who experienced an increase in total cholesterol and a transient elevation of triglycerides following mirtazapine exposure (Nicholas et al., 2003). Of more concern was the discovery of a case report documenting acute pancreatitis and diabetic ketoacidosis secondary to massive triglyceridaemia following the commencement of mirtazapine for depression (Chen et al., 2003). This prompted the decision to cease mirtazapine in this patient.

Within 4 weeks, lipid levels had returned to 5.3 mmol/L (cholesterol) and 6.0 mmol/L (triglycerides). Glycaemic control during the same period was very good (HbA1c 6.1%), and body weight on discharge was 69.8 kg.

Post-marketing surveillance of mirtazapine reports a resultant dyslipidaemia rate of between 1:1000 and 1:10,000 (MSD Australia, 2011). However, the massive scale of the increase, the high potential for cardiovascular sequelae, and the possible development of life-threatening pancreatitis at such levels should lead to the consideration of monitoring serum lipids, and other metabolic markers, in all patients receiving treatment with mirtazapine.

Interestingly, despite an increasing awareness of the need to monitor for metabolic syndrome in psychiatric patients with conditions other than psychosis (McIntyre et al., 2012), local clinical practice guidelines do not reflect this, and would do well to be updated.