Out Of The Pipeline

Transdermal selegiline

Current Psychiatry. 2006 April;5(4):79-83

References

1. Blackwell B, Mabbitt LA. Tyramine in cheese related to hypertensive crises after monoamine-oxidase inhibition. Lancet 1965;62:938-40.

2. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (2nd ed). Available at: http://www.psych.org/psych_pract/treatg/pg/Practice%20Guidelines8904/MajorDepressiveDisorder_2e.pdf. Accessed March 15, 2006.

3. IMS Health National Prescription Audit; 12/04-11/05. Available at: http://www.imshealth.com. Accessed March 15, 2006.

4. Johnston JP. Some observations on a new form of MAO in brain tissue. Biochem Pharmacol 1968;17:1285-97.

5. Youdim MB. Monoamine oxidase inhibitors as antidepressant drugs and as adjunct to L-dopa therapy of Parkinson’s disease. J Neural Transm Suppl 1980;(16):157-61.

6. Bodkin JA, Kwon AE. Selegiline and other atypical MAO inhibitors in depression. Ann Psychiatry 2001;31:385-91.

7. Sunderland T, Cohen RM, Molchan S, et al. High-dose selegiline in treatment-resistant older depressive patients. Arch Gen Psychiatry 1994;51:607-15.

8. Ziemniak JA, Kemper EM, Goodhear M, Azzaro AJ. Pharmacokinetics of selegiline administered via the patch, single oral dose, or intravenous infusion. Poster presented at: Annual Meeting, National Institute of Mental Health, New Clinical Drug Evaluation Unit, May 29, 2001, Phoenix, AZ.

9. Bodkin JA, Amsterdam JD. Transdermal selegiline in major depression: a double-blind, placebo-controlled, parallel-group study in outpatients. Am J Psychiatry 2002;159:1869-75.

10. Amsterdam JD. A double-blind, placebo-controlled trial of the safety and efficacy of selegiline transdermal system without dietary restrictions in patients with major depressive disorder. J Clin Psychiatry 2003;64:208-14.

11. Robinson DS, Moonsammy G, Azzaro AJ. Relapse prevention study shows the long-term safety and efficacy of transdermal selegiline, a new generation MAOI. Poster presented at: Annual Meeting, American College of Neuropsychopharmacology, Dec 11, 2002; San Juan, PR.

12. Robinson DS, Amsterdam JD. Safety and tolerability of selegiline transdermal system 20 mg for treatment of major depression. Poster presented at: Annual Meeting, American College of Neuropsychopharmacology, Dec. 13, 2005, Waikalo, HI.

13. Cole JO, Bodkin JA. Antidepressant drug side effects. J Clin Psychiatry 1990;51(Suppl):21-6.

14. Barrett JS, DiSanto AR, Thomford PJ, et al. Toxicokinetic evaluation of a selegiline transdermal system in the dog. Biopharm Drug Dispos 1997;18:165-84.

Side effects

Transdermal selegiline, 6 mg/d, has been well-tolerated in clinical trials. Inflammation at the application site was the most commonly reported side effect, occurring in 32% to 36% of treatment group subjects compared with 15% to 17% of the placebo groups.^9,10,12 Inflammation was usually mild, but approximately 3% of patients dropped out of one study,¹² citing this effect as the reason. Fair-skinned women are at highest risk for this reaction.

In the 1-year relapse prevention study,¹¹ 12% of treatment group patients reported insomnia compared with 7% of the placebo group. Insomnia incidence was the same in the selegiline and placebo groups during the 6- to 8-week clinical trials.^9,10

Unlike conventional oral MAOIs,¹³ the 6-mg selegiline patch has not been found to impair sexual function, alter appetite, or change body weight or blood pressure compared with placebo.^10-12 The toxicity of the 9- and 12-mg patches has not been studied in humans, but 8 mg/d and 12 mg/d of transdermal selegiline across 3 months were shown not to cause drug toxicity in dogs.¹⁴

Pediatric use

Although transdermal selegiline has not been studied in children and adolescents, the 6-mg patch could benefit some youths with depression. Before starting the drug, discuss with the child’s parents/guardians the FDA’s black box warning describing a possible association between selegiline and increased suicidal behavior in youths. This applies to all antidepressants.

Geriatric use

The patch might also help some older patients with depression. In a double-blind trial of high-dose oral selegiline (60 mg/d) involving 16 older patients (mean age 65.6), both the treatment and placebo groups remained almost free of side effects across 3 weeks.⁷ Although the sample was small, the findings suggest that older patients can tolerate selegiline at high dosages. Side effects also were minimal among treatment-group patients age ≥65 in the yearlong relapse prevention study.¹¹

Treatment adherence rates with transdermal selegiline have been high in published studies, suggesting that the patch’s visibility might reduce the risk of forgetting to take the medication. Observing whether the patch has been changed might help older patients and family members/caregivers keep track of dosing.

Contraindications

As with the oral form, do not prescribe transdermal selegiline to patients taking SSRIs, SNRIs, tricyclic antidepressants, mirtazapine, or bupropion.

When switching antidepressants, allow enough time for the previous agent to “wash out” before starting transdermal selegiline. How much time to allow for wash-out depends on the previous agent’s half-life.

The patch is also contraindicated for patients taking:

carbamazepine or oxcarbazepine
meperidine
analgesics such as tramadol, methadone, and propoxyphene
St. John’s wort
cough syrups containing dextromethorphan
amphetamines, such as mixed amphetamine salts
cyclobenzaprine
or cold remedies or weight-loss products that contain vasoconstrictors, such as pseudoephedrine, phenylephrine, phenylpropanolamine, or ephedrine.

Do not give transdermal selegiline during pregnancy, as its effect on fetal development has not been studied.

Dosing

Start transdermal selegiline at 6 mg/d. Instruct the patient to wear the patch on the upper torso, where vascularity is richer compared with the buttocks and legs. Tell the patient to change the patch daily and to apply it to a different spot each day to prevent inflammation. Consider increasing the dosage after 2 or 3 months if response is unsatisfactory.

For treating first, second, and some third depressive episodes, continue transdermal selegiline for 6 months to 1 year of sustained recovery; consider longer-term maintenance treatment for highly recurrent depression. Transdermal selegiline has not been tapered in clinical trials, and subjects have not reported withdrawal symptoms after 1 year of continuous treatment.

Related resources

Deniker P. The search for new antidepressants and related drugs. In: Tipton KF, Doster P, Benedetti M (eds). Monoamine oxidase and disease. London: Academic Press; 1984:2-8.

Drug brand names

Amphetamine salts, mixed • Adderall
Bupropion • Wellbutrin
Carbamazepine • Tegretol, Equetro, others
Cyclobenzaprine • Flexeril
Meperidine • Demerol
Mirtazapine • Remeron
Oxcarbazepine • Trileptal
Propoxyphene hydrochloride • Darvon
Propoxyphene napsylate • Darvocet
Selegiline (oral) • Eldepryl
Selegiline (transdermal) • EMSAM
Tramadol • Ultracet

Disclosure

Dr. Bodkin receives grant support from the National Institute of Mental Health, Eli Lilly & Co, Jazz Pharmaceuticals, Merck & Co., Organon, Sanofi-Aventis, and Somerset Pharmaceuticals; is a consultant to Bristol-Myers Squibb Co. and Somerset Pharmaceuticals; and is a speaker for Bristol-Myers Squibb Co. He has been principal investigator in several multicenter clinical trials of selegiline.