Metformin in Schizophrenia? Acta Psych Scandi:Oct: 2012


It is well established that individuals with serious mental illness do not live as long as others. Life expectancy is reduced by 20%. Lifestyle factors (poor nutrition, smoking, substance abuse, inactivity) contribute partly to this. Contribution of antipsychotics in this  is increasingly being recognised . In psychotic disorders,these medications are typically started in early  adult life and most often majority remains on them life long. Weight gain and its attendant insulin resistance contribute to 10%  of this group becoming diabetic and more than a third having prediabetes by the time they reach late 30s. This also limit their ability to engage in healthy activities. It can  destroy their confidence and optimism.

How do we deal with this enormous challenge? Curtis J, Newall H, Shiers D and Samaras K make a strong argument for a primary preventive strategy for this.

They clearly state that healthy eating strategies, supervised caloric restriction for those gaining weight and increasing physical activities tailored to the person as fundamental in tackling this problem. The authors argue that we need to consider routine use of Metformin in this group of patients.

 Why Metformin?

It is the first line in treating type 2 diabetes mellitus.It has established efficacy in euglycaemic disorders (eg: polycystic ovary syndrome). Three meta-analyses have shown that Metformin alone or with lifestyle intervention can attenuate weight gain in normoglycaemic patients with psychosis commencing or receiving antipsychotic medications (Newall H et al, 2012). Benefits were evident in the critical early phase following antipsychotic initiation in   drug-    naıve, first-episode psychosis patients, regardless of the antipsychotic used. The review also observed that  Metformin plus lifestyle intervention gave a net weight reduction of 7.8 kg in just  12 weeks. Metformin is successfully used in at risk obese ,non psychotic populations. At least in the short term, Metformin would augment the life style interventions in patients who are being started on antipsychotics.

The authors argue that Metformin should be considered in the severely mentally ill when antipsychotic agents are initiated or in antipsychotic recipients who are overweight, obese or have elevated cardiometabolic risk factors. This early, pro-active intervention along with lifestyle strategies would offer a primary preventative strategy in this most metabolically  vulnerable group of patients.

In the accompanying editorial comment, Prof Taylor wonders why this very sensible idea has not been put forward before now.  The mortality gap between severely mentally ill and general population is not decreasing in spite of claims of better treatments and care. Metformin has now emerged as the choice drug for attenuating and reversing antipsychotic-induced weight gain. Metformin is the most widely prescribed antidiabetic drug. It inhibit hepatic gluconeogenesis, improves insulin sensitivity and increases peripheral glucose uptake.It can reduce the time to development of diabetes in those at high risk of diabetes.It reduces complications in those with diabetes and thus mortality.

Any Adverse effects?

Common problems (>1 ⁄ 10 patients): Nausea, vomiting, abdominal pain and loss of appetite.Majority will have it, but usually resolve over time. Dividing the dose and taking after meals will help.

One serious risk is that of lactic acidosis,more in those with reduced renal function. It is very rare (9/100 000 person years) but mortality is 50% in these cases. Alcohol use along with Metformin can increase the risk of acidosis.With renal function monitoring and alcohol avoidance, Metformin can be prescribed safely. Benefits hugely outweigh this risk.

Prof Taylor  considers  the idea of co-administration of Metformin to a much wider range of patients with severe mental illness as evidently desirable.

Clinical Practice:

Consider Metformin when starting / continuing antipsychotics in patients with  obesity and or other metabolic risk factors. This should be a part of a comprehensive life style intervention.Involve patient and carers in the process. Monitor renal functions and encourage avoiding alcohol.

Summary of the articles:

Considering metformin in cardiometabolic protection in psychosis. Curtis J, Newall H, Myles N, Shiers D, Samaras K.Acta Psychiatr Scand. 2012 Oct;126(4):302-3.

Metformin for schizophrenia: an editorial comment to Curtis J, Newall H, Shiers D, Samaras K. ‘Considering metformin in cardiometabolic protection in psychosis’. Taylor D. Acta Psychiatr Scand. 2012 Oct;126(4):233-4.

One thought on “Metformin in Schizophrenia? Acta Psych Scandi:Oct: 2012

  1. A very good recommendation. It is high time physicians also come up with similar recommendations for the risk groups in general population globally ( where type II DM is reaching epidemic proportions ), to prevent serious and lasting complications.

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