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. Special populations 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 Side effects of the tablet form in conjunction with levodopa 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 signaling, and can be alleviated by reducing the dose of levodopa. The main side effects of the patch form for depression include 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. Interactions Both the oral and patch forms come with strong warnings against combining selegiline with drugs that could produce serotonin syndrome, such as SSRIs and the cough medicine dextromethorphan. Selegiline in combination with the opioid analgesic pethidine is not recommended, as it can lead to severe adverse effects. Several other synthetic opioids such as tramadol and methadone, as well as various triptans, are contraindicated due to potential for serotonin syndrome. Birth control pills containing ethinylestradiol and a progestin increase the bioavailability of selegiline by 10- to 20-fold. High levels can lead to loss of MAO-B selectivity, and selegiline may begin inhibiting MAO-A as well. This increases susceptibility to side effects of non-selective MAOIs, such as tyramine-induced hypertensive crisis and serotonin toxicity when combined with serotonergic medications. Both forms of the drug carry warnings about food restrictions to avoid hypertensive crisis that are associated with MAO inhibitors. The patch form was created in part to overcome food restrictions; clinical trials showed that it was successful. Additionally, in post-marketing surveillance from April 2006 to October 2010, only 13 self-reports of possible hypertensive events or hypertension were made out of 29,141 exposures to the drug, and none were accompanied by objective clinical data. The