Improve Glycemic Control to Extend Lifespan

FEBRUARY 12, 2017
Mental illness dramatically shortens the mean lifespan of those affected. In fact, mental illness has a greater effect on life expectancy than lifelong heavy smoking! Further, severe mental illness has an even larger impact than mental illness overall. Severe mental illness, such as psychotic disorders, particularly decreases patient life expectancy and more than doubles diabetes risk.1

Past estimates found bipolar disorder and schizophrenia can decrease life expectancy by two decades and alcohol abuse by a quarter-century. The gulf between life expectancy of those with and without severe mental illness has widened because the life span gains have lagged among the mentally ill.2 A primary driver of this gap is premature death, therefore the difference in annual death rate shrinks as individual patients survive longer. The results of long-term studies (follow-up greater than 10 years) confirm this finding. Interventions to boost life expectancy need to prevent unnatural death (such as suicide) and delay common age-related killers. Three possible approaches (most effective in combination) are expanding access to care, providing ongoing stable preventive care, and encouraging healthful behaviors.3 Pharmacists in a variety of settings can be integral in this process.

Metabolic syndrome, psychosocial barriers, drug abuse, heightened suicide risk, financial difficulties, and profoundly increased diabetes risk drive the decreased life expectancy of those with severe mental illnesses. Previous reviews of medical interventions considered glycemic outcomes in patients with severe mental illnesses as secondary outcomes only.1

British researchers identified pharmacological and behavioral interventions effective for glycemic control of patients with severe mental illness in a study published on January 5, 2017 by PLoS One.1

The authors selected randomized controlled trials enrolling patients 18 years and older with schizophrenia, bipolar disorder, psychosis, or other non-organic psychotic disorders. The researchers noted incidence of diabetes, HbA1c or fasting glucose in patients who did not have diabetes and in those patients with diabetes, the researchers noted HbA1c, fasting glucose, weight, body mass index, and diabetic complications.

Study diabetes medications included insulin, metformin, pioglitazone, and rosiglitazone (limited availability during the study period). Amantadine, orlistat, reboxetine, sibutramine, topiramate, and zonisamide were the weight loss medications. Amantadine decreases prolactin levels, orlistat prevents dietary fat absorption, reboxetine is an antidepressant improving appetite control, sibutramine is a stimulant, and the final two options are weight loss-promoting antiepileptic medications.

Patients used olanzapine, quetiapine, ziprasidone, and aripiprazole antipsychotics. Olanzapine (along with clozapine) are the most likely to cause metabolic syndrome and weight gain. Ziprasidone and aripiprazole are 2 of the lowest-risk antipsychotics. Quetiapine’s risk of these adverse outcomes is tied with risperidone and paliperidone between olanzapine and aripiprazole.4

The other glycemic control medications included fluvoxamine, memantine, phenylpropanolamine, melatonin, naltrexone, crocin, and DHEA. Fluvoxamine decreases the necessary antipsychotic dosage, memantine decreases binge eating, and phenylpropanolamine is a stimulant.  Melatonin and naltrexone impact metabolism regulation. Crocin is an active ingredient of saffron extract claimed to improve patient’s lipid profile. DHEA increases insulin sensitivity to avoid or minimize metabolic syndrome.

Both pharmacological and behavioral interventions enhanced fasting blood glucose control. Switching between antipsychotics and augmenting metformin therapy improved HbA1c. However improvement of this laboratory finding needs months to take effect (a surrogate of the mean blood glucose of the past three months) therefore every trial except one, lasting more than six months, found no effect on HbA1c. The addition of antipsychotics, especially those most associated with metabolic syndrome, counteracted all interventions (particularly pharmacological kinds). The addition of weight loss medications had little effect on HbA1c or fasting blood glucose in the included studies.

Unsurprisingly, regular exercise improved the effects of pharmacological interventions. Also diabetes and weight loss medications had a smaller effect on patients who did not have diabetes. The analysis authors could not adequately identify the precise difference in effect size because of a lack of data.

Long-term programs that select the least metabolic syndrome-inducing antipsychotic, optimize metformin use, and include physical exercise best improved glycemic control in patients with severe mental illnesses. Complicated therapies are difficult to follow for the general population and just as, if not more, difficult in the severely mentally ill. Simplifying therapy by avoiding polypharmacy, difficult-to-store medications, and changeable therapies improves adherence.

Metformin and the selection of the least metabolic syndrome-inducing antipsychotic are particularly useful pharmacologic interventions for improved glycemic control in patients with severe mental illness. Pharmacists can intervene on patients’ medications to promote glycemic control and improved life expectancy.

Works Cited
  1. Taylor J, Stubbs B, Hewitt C, Ajjan RA, Alderson SL, Gilbody S, et al. The effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in adults with severe mental illness: a systematic review and meta-analysis. PLoS ONE. 2017; 12(1): e0168549. doi:10.1371/journal.pone.0168549.
  2. Chesney E, Goodwin GM, Fazel S. Risks of all-cause and suicide mortality in mental disorders: a meta-review. World Psychiatry. 2014; 13(2): 153-160.
  3. Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry. 2015; 72(4): 334-41. doi: 10.1001/jamapsychiatry.2014.2502.
  4. Muench J, Hamer AN. Adverse effects of antipsychotic medications. Am Fam Phys. 2010; 81(5): 617-622.


Daniel Holland, PharmD
Daniel Holland, PharmD
Daniel Holland, PharmD, is a graduate and medical writer from the University of Connecticut School of Pharmacy. Connect with him on LinkedIn or at daniel.holland222@gmail.com
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