Psychiatric pharmacotherapy traditionally has involved pills, liquids, and shots. Prescribers now can add skin patches to that list.
Earlier this year the FDA approved the transdermal delivery (i.e., through the skin) of two psychiatric drugs:
EMSAM was approved for treatment of major depressive disorder in adults. EMSAM delivers selegiline, a monoamine oxidase inhibitor (MAOI), transdermally (figure 1).
Daytrana was approved for treatment of ADHD. Daytrana is a once-a-day transdermal treatment using methylphenidate, a central nervous system stimulant (figure 2).
While these are the first approved transdermal applications of psychiatric drugs, medications have been delivered transdermally for more than two decades, including antimotion sickness and smoking-cessation drugs. According to the Institute for Safe Medication Practices, an estimated 12 million people worldwide use medicated patches for a variety of ailments, involving more than 30 different drugs.
Transdermal delivery of psychiatric medications will be useful in patients who will not or cannot swallow pills, notes Joseph Biederman, MD, chief of the clinical and research program in pediatric psychopharmacology at Massachusetts General Hospital and a professor of psychiatry at Harvard Medical School.
Commenting on Daytrana, Dr. Biederman notes that “From the time you take the patch off, the effect lasts about two hours, so if you want an eight-hour effect, you can take it off after six hours.” Thus, patients and their caregivers can decide how long they want to keep the patch on, depending on a patient's needs on a particular day. A new patch is used every day.
“Daytrana offers true all-day therapy,” asserts Noven Pharmaceuticals Vice-President Joseph Jones (Noven manufactures Daytrana for Shire, plc). “It's not the only product that provides all-day therapy, but no pill provides the same level of dosing flexibility.” Since therapy can be discontinued as early as needed by removing the patch, Jones explains, Daytrana offers an advantage that pills don't.
In addition, says Andrew Adesman, MD, chief of development and behavioral pediatrics at Schneider Children's Hospital in New Hyde Park, New York, Daytrana should appeal to some parents, who can apply the patch in the morning and remove it in the late afternoon or early evening.
With EMSAM, medication is absorbed over an extended period, which minimizes exposure to the digestive system, notes Bristol-Myers Squibb spokesman Craig Stoltz (Bristol-Myers Squibb and Somerset Pharmaceuticals developed EMSAM). This is important because MAOI antidepressants inhibit intestinal enzymes needed to break down tyramine, which is found in some foods and beverages such as tap beer and aged cheese. Large amounts of tyramine absorbed systemically can lead to a sudden increase in blood pressure and may require immediate medical attention. For those reasons, patients taking MAOIs for major depression are advised to avoid foods and beverages high in tyramine. While no tyramine dietary modifications are required at EMSAM's starting and target dose of 6 mg/24 hours, they are needed for EMSAM's 9 mg/24 hours and 12 mg/24 hours doses.
Transdermal patches do have their downsides. For example, Daytrana's onset of action is not very rapid, notes Dr. Adesman. Daytrana generally requires two hours to take effect, compared with only 30 to 45 minutes for most oral ADHD medications. It also turns out, he adds, that there is a fair amount of variability in children's absorption rates. “A significant percentage of patients may not have much response in even two hours,” explains Dr. Adesman. In such cases the patch can be applied earlier. But that, in turn, could disrupt routines for children and parents, and result in the effects not carrying the child through the afternoon.
Figure 1. Image courtesy of Bristol-Myers Squibb. Note that the photo was taken against a blue background; the patch itself is transparent.
In addition, while Daytrana has been promoted as allowing better treatment compliance monitoring since it's so easy to tell if a child is wearing the patch, that's not usually a big issue with schoolkids, according to Dr. Adesman. And children could remove the patch at any point during the day. “It's as much a liability as an asset,” he concludes.
Similar concerns about transdermal delivery have been expressed about EMSAM.
More to Come?
While other psychiatric medications have not been approved for transdermal delivery, transdermal clonidine (an antihypertensive) has been used for off-label treatment of ADHD, using a patch once a week or for five days, notes Dr. Biederman.
Noven is developing a second transdermal patch for ADHD (also to be marketed by Shire), Jones notes. The new patch, which is in preclinical development, would deliver amphetamine transdermally.