A weight off the mind: Clozapine and profound weight loss

To the Editor

We report an unusual case of greater than 30% loss of body mass in a patient on the antipsychotic medication clozapine.

In February 2013, a 56-year-old Aboriginal Australian with treatment refractory paranoid schizophrenia was admitted for investigation of profound weight loss and dizziness. Past medical history included previous alcohol abuse (ceased around the time of clozapine commencement) and cigarette smoking but no significant chronic medical issues. There had been a measurable improvement in the patient’s mental state on clozapine 300 mg daily, his only medication.

Clozapine, the first SDA (serotonin–dopamine antagonist) to be approved, remains the treatment of choice for refractory schizophrenia. Weight gain is a frequent side effect of clozapine with between 20% and 80% of patients gaining greater than 10% baseline body weight (Iqbal et al., 2004; Young et al., 1998).

Interestingly, the patient’s weight on admission was 63 kg (BMI of 20.6 kg/m²), a loss of 30 kg of body weight over the 6 months since commencing on clozapine. At this time, he also complained of severe dizziness but no other systemic symptoms. There were no obvious delusional or affective causes for his weight loss.

There was significant concern as to the potential cause of such profound and rapid weight loss and the local medical team was engaged to assist with a thorough work-up. Physical examination revealed a postural blood pressure drop of 30 mmHg systolic and 15 mmHg diastolic but no other abnormalities. A battery of investigations was arranged. In spite of exhaustive imaging and laboratory testing, the only abnormality identified was vitamin D deficiency at 28 nmol/L. In view of the patient’s age, lifestyle and illness factors he was noted to be surprisingly healthy.

In the absence of an identified organic cause, clozapine was considered the most likely culprit to explain the patient’s weight loss and dizziness. Clozapine is known to cause orthostatic hypotension in approximately one-quarter of patients (Stroup et al., 2009); however, this effect is usually transient and associated with commencement or dosage increases. We suspect that this patient’s severe dizziness resulted in reduced mobility and therefore prolonged caloric restriction and reduced physical activity with resultant fat and muscle loss. This would also provide an explanation for the patient’s vitamin D deficiency through lack of sun exposure – quite an achievement in northern Australia.

The patient’s hypotension did not respond to the initial management of a dose reduction in clozapine. This did, however, result in a gradual deterioration in mental state. A literature search demonstrated a paucity of evidence for management of persistent hypotension in patients on clozapine. First line steps of adding salt tablets and increasing fluid intake failed to improve the hypotension: it was clear a more innovative approach was needed.

Two published case reports were found describing clozapine-related hypotension being treated with fludrocortisone (Testani, 1994). This practice appears to have developed from the use of fludrocortisone in the treatment of other causes of postural hypotension such as Parkinson’s disease.

With the addition of fludrocortisone (gradually titrated to 200 mcg mane), the patient’s clozapine was returned to the previous dose of 300 mg daily. This resulted in a gradual improvement in mental state and no ongoing hypotension or dizziness. No significant side effects were identified from the fludrocortisone and the patient was discharged back to the community team with a stable mental state. His weight increased while in hospital from 63 kg to 69 kg.

To our knowledge, this is the first published example of clozapine-induced hypotension leading to weight loss. Hypotension is not an uncommon side effect of this important psychiatric medication and we suggest that fludrocortisone may be an appropriate pharmacological agent for use in patients with persistent, troublesome orthostatic hypotension.