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:

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.

Concerns

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.

Another concern is skin reactions. Daytrana is associated with redness at its application site, particularly if left on longer than recommended, notes Dr. Adesman. “Anything on a child's skin may cause a reaction. Parents have to remain alert and not leave it on longer than nine hours. I can imagine some households where the parents would forget to take it off,” he comments.


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.

From Bristol-Myers Squibb's viewpoint, EMSAM was “an opportunity to make an impact in treatment of patients,” says Stoltz. But while the company's partnership with Somerset offered a way to provide a treatment option for patients with major depression, Bristol-Myers Squibb does not have any other late-stage technology at present involving transdermal delivery of psychiatric medications.

FDA spokeswoman Kimberly Rawlins declined to comment on whether other transdermal medications used to treat behavioral health conditions are under consideration.

How Will Payers React?

Since transdermal patches are just now becoming available to treat behavioral health conditions, it's not clear how managed care firms and third-party payers will react to either EMSAM or Daytrana.

Dr. Adesman says we may not know how payers will react to Daytrana for a while. “I don't think this will be a first-line choice in terms of treatment for ADHD,” he says, “so I'm not sure we'll get an immediate response from managed care firms.”

Roy Boorady, MD, assistant professor of psychiatry and clinical coordinator of the psychopharmacology service at the New York University Child Study Center, hasn't heard about any payer concerns for accepting claims for FDA-approved patches. “We have seen insurance companies pay for other patches,” he notes.

Time will tell, however, whether insurers add transdermal drugs to their formularies, given that less expensive pill forms are available. Consider that two pharmacies surveyed in two states are charging $179.99 for a 30-day supply of Daytrana (15 mg methylphenidate), but a similar drug in tablet form, Concerta extended release (18 mg methylphenidate), costs $123.99 for a 30-day supply.