“Looking at all the data we do have,” he said, “it certainly seems like the risk is low, about one death per 100,000 per year.”
However, in what Dr. Carlson described as “the earthquake of several months ago,” a case-control study found that youths who died of sudden cardiac death were 7.4 times more likely to be taking stimulants for ADHD than were youths who died as passengers in automobile accents (Am. J. Psychiatry 2009;166:992-1001).
“The study had a bunch of flaws, pointed out in editorials and letters since,” Dr. Carlson noted. “The FDA has not changed its policy as a result.”
With a large study now underway aimed at replicating the data in that 2009 study, Dr. Carlson said, “I would surely hope that with an n of 100,000, we should get a good answer. So stay tuned.”
Another endocrine risk reviewed by Dr. Carlson was the stimulation of excess prolactin associated with antipsychotics, a condition that not only stimulates lactation but also can inhibit penile erections, decrease libido, and cause a variety of other adverse effects.
Dr. Carlson cited unpublished data from a study by Dr. Christoph U. Correll, showing that the 3-month incidence of missing at least one menstrual period in 152 female youths varied widely, from 21.7% on olanzapine, and 30% on risperidone, to 2.9% on quetiapine and 8.3% of aripiprazole. Risperidone also had the highest incidence, at 6.3%, associated with galactorrhea in 345 postpubertal youth.
“You need to ask your patients about these potential side effects,” Dr. Carlson said. “A lot of teenagers will not volunteer this information. You'll have to drag it out of them little by little. All of these things are sensitive issues in teenagers.”
If signs and symptoms of hyperprolactinemia are confirmed by a blood test, switching to a more prolactin-sparing agent, or reducing the dose, are recommended. But, he added, “If you can't stop or switch, you can combine your drug with one that is prolactin neutral or lowering, such as aripiprazole.” He cited a paper (Am. J. Psychiatry 2007;164:1404-10) that found that adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes.
Finally, Dr. Carlson noted that the incidence of polycystic ovary syndrome (PCOS) was found to be 10.5% in bipolar patients taking valproate, compared with 1.4% of those taking any other antipsychotic medication (Biol. Psychiatry 2006;59:1078-86).
With all female bipolar patients, he said, “Ask about their menstrual function,” Dr. Carlson recommended. “Ask before starting a drug and then each time you see them. Ask about acne and facial or body hair. They're not going to volunteer this very often.”
If symptoms of PCOS emerge, he said: “Arrange for them to get counseling on diet and exercise. You could set them up to see a primary care physician, gynecologist, or endocrinologist. There are treatments besides stopping the drug.”
Dr. Carlson disclosed financial relationships with pharmaceutical companies, including Eli Lilly; Janssen L.P.; Ortho-McNeil-Janssen Pharmaceuticals; Otsuka America Pharmaceutical; Bristol-Myers Squibb; Cephalon Inc.; McNeil Pediatrics, a division of McNeil-PPC; and Shire U.S.