Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selegiline HCl, 10 mg per day has been reported to improve attention and episodic memory in Parkinson's disease and early Alzheimer's disease. Selegiline also improves motor reaction times in Parkinson's and subjective feelings of increased vitality, euphoria and energy. At doses of between 10 and 40 mg a day it has also been shown to improve depression particularly when psychomotor retardation is prominent and anxiety minimal.
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PMID:Selegiline hydrochloride and cognition. 180 44

Selegiline is a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B). It also inhibits the reuptake of catecholamines into the presynaptic nerve and enhances the synthesis of dopamine by blocking the presynaptic dopamine autoreceptors. Thanks to these properties it potentiates and prolongs the duration of action of levodopa. Several clinical trials have shown its efficacy as an adjuvant to levodopa therapy. Improvement in parkinsonian disability and reduction of fluctuations in disability can be achieved by adding selegiline to the prevailing levodopa therapy. End-of-dose type fluctuations, in particular, react favourably to selegiline. Side-effects of the therapy can be managed by reducing the dose of levodopa. According to preliminary studies selegiline may also have some benefit as monotherapy in de novo parkinsonian patients. High doses of selegiline have been found to have some antidepressant efficacy, especially in patients with nonendogenous depression. It may also have an effect on bradyphrenia and some symptoms of cognitive dysfunction and dementia. In animal models selegiline has been shown to prevent parkinsonism caused by MPTP and also to increase the life span of rats. Whether selegiline slows down the progression of Parkinson's disease needs further examination.
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PMID:Selegiline in the treatment of Parkinson's disease. 251 15

The goal of this study was to determine whether selegiline (L-deprenyl), a selective monoamine oxidase B inhibitor and antioxidant, would improve neuroleptic-induced tardive dyskinesia (TD). Thirty-three patients with TD were randomly assigned to selegiline 10 mg/day or placebo for 6 weeks and were assessed at baseline and at weeks 1, 2, 4, and 6 for TD, parkinsonism, akathisia, depression, and positive and negative symptoms. Examinations for TD were videotaped and scored by a rater unaware of the temporal sequence of examination. Twenty-eight subjects completed at least 1 week of treatment; all five dropouts were receiving selegiline. When baseline score and gender were controlled, the group receiving selegiline displayed significantly less improvement of TD compared with the placebo group. The two treatment groups did not differ in any other outcome measure. Selegiline was less effective than placebo in reducing symptoms of TD over a 6-week trial. This may be the result of the dopamine agonist effects associated with selegiline.
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PMID:A placebo-controlled trial of selegiline (L-deprenyl) in the treatment of tardive dyskinesia. 810 52

The French Selegiline Multicenter Trial was carried out in 1990 to investigate whether the disability of de novo patients with parkinsonism could be improved during the first 3 months by monotherapy with selegiline (10 mg/day). A double-blind, randomized, placebo-controlled clinical trial was conducted over 3 months with 93 patients from 13 centers. Symptomatology was assessed on various disease rating scales, including Hoehn and Yahr, Hamilton Depression Rating Scale, Unified Parkinson's Disease rating scale, and Schwab and England scores, as well as self-assessment. Biological and clinical parameters were measured for tolerability, and efficacy was investigated with special reference to the point at which therapy with L-dopa had to be started. Selegiline was significantly superior to placebo on the various motor rating scores, and depressive scores were significantly improved at the end of 3 months. Adverse effects were rare and minor. Therefore, selegiline could be the therapy of choice for the treatment of de novo parkinsonian patients.
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PMID:Symptomatic effect of selegiline in de novo Parkinsonian patients. The French Selegiline Multicenter Trial. 830 6

Selegiline is a selective monoamine oxidase inhibitor used in the treatment of Parkinson's disease. It is estimated that approximately one-half of Parkinsonian patients will develop depression requiring antidepressant drug treatment. Recently, selegiline's package insert was revised to reflect the potential risk of adverse effects when it is used in combination with selective serotonin reuptake inhibitors and tricyclic antidepressants. The objective of our study is to assess the safety of combining selegiline with antidepressants. A retrospective chart review was performed on all 28 patients with Parkinson's disease receiving selegiline and antidepressants concurrently to identify possible drug interactions. Compliance was assessed according to prescription refill records. Suspected adverse reactions with combination therapy were documented. There was a total of 40 selegiline-antidepressant drug combinations involving tricyclic antidepressants (n = 25), selective serotonin reuptake inhibitors (n = 7), trazodone (n = 5), and bupropion (n = 3). One patient receiving fluoxetine developed a reaction consistent with the serotonin syndrome; however, it was never documented as such. No other selegiline drug interactions were found. Adverse effects noted were typical of antidepressant monotherapy. Although no selegiline drug interactions were documented in our study, the concurrent administration of selegiline and selective serotonin reuptake inhibitors should be avoided because of literature-reported interactions. We believe that bupropion, tricyclic antidepressants, and trazodone are reasonable choices in combination with selegiline, although tricyclic antidepressants and trazodone may be reserved as second-line treatments.
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PMID:Retrospective study of selegiline-antidepressant drug interactions and a review of the literature. 916 31

Monoamine oxidase inhibitors (MAOIs) are mainly used in psychiatry for the treatment of depressive disorders and in neurology for the treatment of Parkinson's disease. While the classical, nonselective and nonreversible MAOIs, such as phenelzine and tranylcypromine, are characterised by the risk of inducing a hypertensive crisis when dietary tyramine is ingested, the selective monoamine oxidase-B (MAO-B) inhibitor selegiline (deprenyl) and, even more so, the selective and reversible monoamine oxidase-A (MAO-A) inhibitor moclobemide, are free from this potential interaction. Drug tolerability data for the elderly show that moclobemide is one of the most well tolerated compounds. Selegiline, especially when used in combination with levodopa, can cause anorexia, dry mouth, dyskinesia and, most problematic, orthostatic hypotension. For the traditional MAOIs, phenelzine and tranylcypromine, published data are insufficient to be able to give a conclusive tolerability statement regarding the use of these compounds in elderly people. Although orthostatic hypotension occurs in most patients treated with traditional MAOIs, the incidence in elderly patients with depression does not appear to be greater than that reported with tricyclic antidepressants.
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PMID:Monoamine oxidase inhibitors. A perspective on their use in the elderly. 982 63

Somerset is developing a selegiline transdermal system (STS) for potential use in the treatment of depression. It has also been developed for Alzheimer's disease (AD), Parkinson's disease and attention-deficit hyperactivity disorder (ADHD) [182121], although no development has been reported for AD or ADHD in recent years. Somerset claims the transdermal system could be more effective than the oral formulation of selegiline already marketed [250573]. In May 2001, Somerset filed an NDA with the US FDA for STS for the treatment of depression [410848], however, in March 2002, the company received a 'non-approvable' letter from the FDA requesting additional efficacy data. At this time, Somerset had scheduled a meeting with the FDA to review and clarify their comments [456735]. Selegiline will be co-promoted in the US by Watson, under the terms of a previous agreement [275389].
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PMID:Selegiline transdermal system Somerset. 1221 21

Monoamine oxidase inhibitors (MAOIs), which ushered in the modern era of psychopharmacology in the 1950s, have remained useful in the treatment of depression despite important safety concerns, such as acute hypertensive episodes brought on by ingestion of foods with high-tyramine content. Experience has shown that MAOIs are broadly effective in the treatment of depressive disorders, including atypical, chronic, and double depressions. Newer selective and reversible inhibitors of the two forms of mitochondrial monoamine oxidase (MAO) enzymes, MAO-A and MAO-B, have been developed in an effort to improve the safety and tolerability of MAOIs. Selegiline, a selective inhibitor of MAO-B has been shown to be effective in the treatment of depression at higher oral doses where selectivity for MAO-B is lost. Transdermal delivery of selegiline bypasses first-pass metabolism and avoids impairment of the gastrointestinal barrier provided by MAO-A of the gastrointestinal mucosa. Studies have shown that the selegiline transdermal system (STS) does not significantly affect sensitivity to ingested tyramine, unlike tranylcypromine, which markedly increases sensitivity. STS has been found to be efficacious in the treatment of patients with major depression in placebo-controlled trials, without the need for dietary precautions. The favorable safety profile of STS should allow this MAOI to be a broadly used antidepressant drug.
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PMID:Monoamine oxidase inhibitors: a new generation. 1247 70

Monoamine oxidase inhibitors (MAO-I) have been useful in the treatment of both psychiatric and neurological disorders over centuries. Here we focus on the development of this drug treatment. Focus is given on the use of irreversible MAO-I's as well as on reversible ones. Benefit and side effects are reported for Parkinson's disease, Alzheimer's dementia, depression syndrome and panic disorders. The preclinical and clinical effects of selegiline with regard to neuroprotection are highlightened and the conclusion is drawn that there is good evidence for a clinical neuroprotective capacity based on the assumption that the 50 percent recovery of MAO-B is obtained already after a 10 days withdrawal of selegiline. There is also a focus on selegilines metabolism to amphetamine and metamphetamine. In order to avoid any such effects of metabolic compounds on the cardiovascular system Zydis Selegiline, a melt-tablet avoid of major metabolism to amphetamine and metamphetamine is described in detail. Developments in MAO-I research are discussed in detail as there are moclobemide, lacabemide, rasagiline. Interactions of MAO-I' with tricyclics and serotonin selective reuptake inhibitors (SSRI's) are described as there is mentioning of interactions of MAO-I's with other compounds in general. Tables and figures report on clinical studies and on pharmacological properties of MAO-I's.
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PMID:Clinical applications of MAO-inhibitors. 1527 66

The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to concerns about food and drug interactions and waning physician experience. Evidence indicates that MAOIs are effective in depressive disorders, in particular depression with atypical features. Efforts to address safety issues have led to the development of more selective and reversible MAOIs, such as moclobemide. Selegiline, a selective monoamine oxidase B inhibitor, has been approved for the adjunctive treatment of Parkinson's disease at low doses. At higher doses, oral selegiline is also effective in major depressive disorder (MDD) but loses its selectivity and has the potential for tyramine interactions. To overcome these problems, a transdermal formulation of selegiline, the selegiline transdermal system (STS), was developed with novel pharmacokinetic and pharmacodynamic properties. Compared with oral administration, transdermal selegiline leads to sustained plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain and decreasing metabolite production. In addition, STS allows targeted inhibition of central nervous system monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in the gastrointestinal and hepatic systems, thereby reducing the risk of interactions with tyramine-rich foods (the "cheese-reaction"). Clinical trials have found 6 mg/24 hours of STS to be effective in MDD without the need for dietary restrictions. The efficacy and safety profile of STS supports its use in MDD. It is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants. However, more research is needed. Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs.
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PMID:Transdermal selegiline: the new generation of monoamine oxidase inhibitors. 1664 41


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