Selegiline

Selegiline, also known as L-deprenyl, is a substituted phenethylamine. At normal clinical doses, it is a selective irreversible MAO-B inhibitor. In larger doses it loses its specificity and also inhibits MAO-A. It is available in pill form under many brand names and is used to reduce symptoms in early-stage Parkinson's disease. A transdermal patch (brand name, Emsam) is used to treat depression. In its pill form, selegiline is used to treat symptoms of Parkinson's disease. It is most often used an adjunct to drugs such as L-DOPA, although it has been used off-label as a solo treatment. The rationale for adding selegiline to levodopa is to decrease the required dose of levodopa and thus reduce the motor complications of levodopa therapy. Selegiline delays the point when L-DOPA (levodopa) treatment becomes necessary from about 11 months to about 18 months after diagnosis. There is some evidence that selegiline acts as a neuroprotective and reduces the rate of disease progression, though this is disputed. Selegiline has also been used off-label as a palliative treatment for dementia in Alzheimer's disease. Selegiline is also delivered via a transdermal patch used as a treatment for major depressive disorder. A quantitative review published in 2015 found that for the pooled results of the pivotal trials, the number needed to treat (a sign of effect size, so a low number is better) for the patch for symptom reduction was 11, and for remission, was 9. The number needed to harm (inverse of the NNT, a high number here is better) ranged from 387 for sexual side effects to 7 for application site reaction. With regard to the likelihood to be helped or harmed (LHH), the analysis showed that the selegiline patch was 3.6 times as likely to lead to a remission vs. a discontinuation due to side effects; the LHH for remission vs. incidence of insomnia was 2.1; the LHH for remission vs. discontinuation due to insomnia was 32.7. The LHH for remission vs insomnia and sexual dysfunction were both very low. For all human uses and all forms, selegiline is pregnancy category C: studies in pregnant lab animals have shown adverse effects on the fetus but there are no adequate studies in humans. Side effects of the pill form include, in decreasing order of frequency, nausea, hallucinations, confusion, depression, loss of balance, insomnia, increased involuntary movements, agitation, slow or irregular heart rate, delusions, hypertension, new or increased angina pectoris, and syncope. Most of the side effects are due to a high dopamine activity, and can be alleviated by reducing the dose of levadopa. The main side effects of the patch form for depression included application-site reactions, insomnia, diarrhea, and sore throat. The selegiline patch carries a black box warning about a possible increased risk of suicide, especially for young people, as do all antidepressants since 2007.