Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seligiline, a monoamine oxidase inhibitor, has been previously approved by the US FDA for adjunctive treatment of Parkinson's disease. At present, it has been found to be effective in a transdermal system when administered daily in the treatment of major depressive disorder. The minimum dosage of 6 mg/24 h was effective in two trials; this dosage did not require any dietary precautions. Higher doses of 9 mg/24 h and 12 mg/24 h may also not require restrictions, however, current data is insufficient. Furthermore, a randomized 52-week prevention study found significant benefits for continuance of this treatment. There are several types of safety data available. First, there have been no reports of hypertensive crisis in any patient receiving selegiline via this transdermal system at any of the three doses. Tyramine challenge studies have found a comfortable cushion of safety at selegiline doses of 6 mg/24 h. Other side effects include a slightly higher rate of orthostatic hypotension, insomnia and, most frequently, application site reactions. There are no significant effects on weight or sexual side effects. In terms of drug interactions, carbamazepine was found to significantly increase seligiline levels (however, carbamazepine should be contraindicated). Direct sympathomimetics may be safe, but indirect ones are thought to put the patient at risk. Finally, due to risk of serotonin syndrome, other medications contraindicated include: selective serotonin re-uptake inhibitors, serotonin-noradrenaline re-uptake inhibitors and multiple analgesics - in particular meperidine. To prevent toxic drug interactions at initiation of seligiline transdermal system therapy, all mediactions that are at risk should be completely stopped a minimum of 4-5 times their respective half-lifes for full elimination. This is generally a time period of 1 week. Upon stopping treatment with selegiline, 2 weeks should pass prior to beginning any medication at risk for drug interactions.
 ...
PMID:Seligiline transdermal system in depression. 1716 7

Although older monoamine oxidase inhibitors (MAOIs) are effective in the treatment of depressive disorders, they are underutilized in clinical practice due to main concerns about interaction with tyramine-containing food, and side effects. Efforts to address these safety issues led to the development of a transdermal formulation of selegiline, called selegiline transdermal system (STS). STS has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depression. Transdermal administration of selegiline bypasses gastrointestinal absorption and first-pass metabolism. Therefore, STS permits inhibition of monoamine oxidase (MAO)-A and MAO-B enzymes in the brain while preserving the activity of MAO-A in the gastrointestinal system, thereby minimizing the risk of possible interactions with tyramine-rich foods. Tyramine challenge tests have confirmed that dietary modifications are not required with the 6 mg STS. The FDA has required dietary modifications with the 9 mg and 12 mg STS. Compared to oral administration, transdermal selegiline leads to sustained (minimal peak-trough fluctuations) plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain. The efficacy of STS has been established in several short-term and one long-term randomized controlled trials. In clinical trials, application site reactions and insomnia were observed more frequently with STS than placebo. Rates of orthostatic hypotension, sexual dysfunction and weight gain were comparable between STS and placebo. STS is a new generation of MAOI with superior safety profile to older MAOIs. It increases the pharmacological options available to treat depressive disorders and may benefit patients with major depression with atypical features and resistant depression. It is important for health-care professionals to be informed about the properties of STS.
 ...
PMID:Transdermal selegiline. 1761 8