Kate Johnson

October 01, 2012

October 1, 2012 (Montreal, Canada) — Body weight should be a central consideration in the choice of psychiatric medication for patients with comorbid mood and metabolic disorders, new recommendations suggest.

The new emphasis reflects emerging evidence that excess weight — a growing problem in this patient population — has a direct negative impact on cognitive function and mood, Roger McIntyre, MD, lead author of the recommendations, told delegates attending the Canadian Psychiatric Association (CPA) 62nd Annual Conference.

"The excess weight that you're seeing in patients doesn't just have implications for cardiovascular health, it also has implications for brain health," said Dr. McIntyre, who is professor of psychiatry at the University of Toronto and head of the Mood Disorders Psychopharmacology Unit at University Health Network in Toronto.

In a recent study comparing normal weight (body mass index [BMI] of 18.5 - 24.9 kg/m2) and overweight/obese (BMI ≥ 25.0 kg/m2) patients with bipolar disorder, Dr. McIntyre and his team found that overweight patients scored significantly lower (P < .05) on a verbal fluency test.

Similarly, studies show that compared with mood disorder patients of normal weight, those who are overweight or obese exhibit greater chronicity and severity of depression, lower psychosocial functioning, and more suicide attempts, Dr. McIntyre said.

"Biggest Offenders"

"Perhaps the increased obesity that we're seeing in our population may be changing the phenotype of bipolar," he suggested. "Where are all the euphoric manic patients? Not in my office anymore. We see dysphoric patients."

Although weight monitoring is recommended in mood disorder patients, the survey conducted by Dr. McIntyre's group showed that among almost 5000 patients with schizophrenia and bipolar disorder, fewer than 30% were ever evaluated for their weight.

However, because psychiatric medications are one of the "biggest offenders" in weight gain among this population, "the clinician needs to consider both short- and long-term weight-gain potential and the psychotropic agent's effect on adipose tissue distribution," according to the recommendations.

Most atypical antipsychotics cause varying degrees of weight gain, whereas weight gain with some antidepressants, such as mirtazapine and paroxetine, "often is slow but inexorable," the authors write.

"Replacing a weight-gain offending agent with a weight-neutral/favorable medication is recommended if the index agent's overall therapeutic value is unfavorable or equivocal," they add.

"I think the days are coming to an end where we're going to strongly endorse a highly weight-gain-promoting medication if an alternative exists. Now the field is beginning to change, and some of the algorithms are beginning to change in terms of selecting medications based on this outcome," said Dr. McIntyre.

However, he emphasized that psychotropic agents associated with weight gain should not be discontinued if they are judged to provide "optimal illness control."

Targeted Weight Loss

Although cognitive-behavioral strategies and diet should be considered first-line therapy for obesity, medications specifically targeting weight loss should also be considered, said Dr. McIntyre.

Second-line considerations include metformin, topiramate, modafinil, orlistat, and zonisamide, and third-line considerations include liraglutide, nizatidine, amantadine, phentermine, and a naltrexone/buprion combination.

"If behavioral strategies or substitution for a psychotropic agent associated with less weight gain prove unsuccessful, clinicians may consider using bariatric medicine," according to the recommendations.

"When you have patients in your office who have excess weight, what they have is the largest endocrine gland in the body, and that endocrine gland, the adipocytes, are synthesizing and secreting a variety of proteins that have a depressogenic effect and are toxic to brain health," explained Dr. McIntyre, adding that the link between depression and cognitive impairment may be mediated in part by disturbances in insulin/glucose homeostasis.

"What's driving some of the cognitive impairment in persistent mental illness is insulin resistance."

"There is definitely a direct correlation between weight gain and cognitive dysfunction, I see it all the time," commented Siva Devarajan, MD, who attended the presentation.

"Big Price to Pay"

"We are partly responsible because we prescribe these medications — it's a big price to pay," said Dr. Devarajan, who is consultant psychiatrist at the Chatham-Kent Health Alliance in Chatham, Ontario, and adjunct professor of psychiatry at the University of Western Ontario in London, Ontario.

He said that although he counsels lifestyle modification, it is "easier said than done," and he also prescribes weight loss medications. "Metformin has a very nice side-effect profile, it is not metabolized by the liver, and topiramate is a good drug, but if you give more than 100 mg, it can cause cognitive dysfunction," he said.

Dr. McIntyre is on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Ortho, Lundbeck, Merck, Pfizer, and Shire; he is on speakers bureaus for AstraZeneca, Eli Lilly and Company, Janssen-Ortho, Lundbeck, Merck, Otsuka, and Pfizer; he is involved in CME activities with AstraZeneca, Bristol-Myers Squibb, CME Outfitters, Eli Lilly and Company, Lundbeck, Merck, Otsuka, Pfizer, and the Physicians' Postgraduate Press; and he receives research grants from AstraZeneca, Eli Lilly and Company, Forest, Janssen-Ortho, Lundbeck, Pfizer, Sepracor, and Shire. Dr. Devarajan did not disclose any relevant financial relationships.

Canadian Psychiatric Association (CPA) 62nd Annual Conference. Abstract S14c. Presented September 29, 2012.