NEW YORK – When prescribing second-generation antipsychotic medications, physicians should start with the agents in this class least likely to cause metabolic adverse effects and only move to prescribing psychotropics with more frequent metabolic effects when necessary, Dr. David C. Henderson said at the meeting sponsored by the American Diabetes Association.
"If we can get patients off the offending drugs and onto more neutral drugs, their risk [for cardiometabolic adverse events] would be much better," said Dr. Henderson, a psychiatrist at Harvard University and director of the schizophrenia, weight reduction, and glucose metabolism research program at Massachusetts General Hospital in Boston.
Dr. David C. Henderson
The two worst offenders of the second-generation antipsychotics are clozapine (Clozaril) and olanzapine (Zyprexa). Both drugs cause most patients to gain weight over a prolonged period of time – up to 3.5 years – and they also impair insulin sensitivity. They also pose an "extremely high risk for triggering types 2 diabetes," a risk Dr. Henderson likened to the diabetes risk faced by Pima Indians. He estimated that about a third of patients on clozapine develop type 2 diabetes. A significantly more neutral option is risperidone (Risperdal and also available in generic formulations). The drugs with the most benign profiles are ziprasidone (Geodon) followed by aripiprazole (Abilify), Dr. Henderson said in an interview. The danger that these drugs pose of causing type 2 diabetes "is not a class effect" and, in fact, their risk for this adverse effect is quite variable.
Prescribing these agents with awareness of their relative dangers for triggering weight gain and dampening insulin sensitivity has become more critical in recent years as "use of these drugs has risen dramatically," he said. As a class, second-generation antipsychotics are now prescribed for a range of psychiatric illnesses, including mood disorders and posttraumatic stress disorder. "Antipsychotics are everywhere," he noted.
In addition, patients with psychiatric illness are inherently vulnerable to the consequences of cardiometabolic derangements because cardiovascular disease is the most frequent cause of death among these patients.
"I start by prescribing the least offensive drug, the safest drug, and then work my way up the risk ladder" if patients fail to respond to less risky agents. "Psychiatrists get stuck on whether one drug works better than another, when in fact none work any better, except possibly clozapine." The more immediate and practical issue is to find the drug that will produce a favorable outcome in each psychiatric patient. "Some patients need a riskier drug, but you should work your way up the ladder" of safety, he said. Once an effective drug is found, the next step is determining what adjunctive treatments the patient needs to counter the adverse metabolic effects and stay healthy while on psychiatric medication.
"I prescribe lipid-lowering medication, and I use metformin to treat insulin resistance. I also follow the patient’s hemoglobin A1c level," and he also repeatedly promotes to patients their need to maintain a healthy diet and exercise, Dr. Henderson said.
Dr. Henderson said that he has been a consultant to Merck and Pfizer and that he has received research support from Janssen and Johnson & Johnson.