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Re: Deprenyl/Selegiline! :) » Jacob

Posted by wingedcat on February 3, 2003, at 14:04:21

In reply to Re: Deprenyl/Selegiline! :), posted by Jacob on February 3, 2003, at 12:03:09

1mg Selegiline is a very low dose. I am not a doctor so when I say you shouldn't have problems I might not be right. It is an MAOI, at that level it probably only inhibits MAO-B so you should be okay. It has caused serious problems combined with SSRI's, though. I presume this was with a MAO-A dose (over 10mg) but since they don't say I can't be sure.


[Serotonin syndrome: report of a fatal case and review of the literature]
Bilbao Garay J, Mesa Plaza N, Castilla Castellano V, Dhimes Tejada P.
Servicio de Medicina Interna, Fundacion Hospital Alcorcon, Madrid, Spain.

We report here the case of a patient with fluoxetine and selegiline induced serotonin syndrome, which presented as encephalopathy, generalized myoclonias, fever, stiffness and sweating, complicated with acute renal failure, rhabdomyolysis and disseminated intravascular coagulation findings. The patient died 6 days after admission. This syndrome is discussed, with an analysis of its causes, pathophysiology and therapy. A special emphasis is placed on the clinical issues and differential diagnosis with the malignant neuroleptic syndrome and other clinical entities with which it could be mistaken. General recommendations are provided to avoid this poorly characterized syndrome that, as in our patient, may have a fatal outcome.

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Possible serotonin syndrome arising from an interaction between nortriptyline and selegiline in a lady with parkinsonism.

Hinds NP, Hillier CE, Wiles CM.
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Drug interactions of clinical significance with selective serotonin reuptake inhibitors.
Mitchell PB.
School of Psychiatry, University of New South Wales, Sydney, Australia. phil.mitchell@unsw.edu.au

The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) have internationally become the accepted 'benchmark' class of antidepressants. It has become clear, however, that there are a number of clinically significant interactions between SSRIs and other medications. The most frequently described interactions are pharmacokinetic, which are far more prevalent than pharmacodynamic interactions. This article details those medications that may interact significantly with the SSRIs, and provides clinical guidelines for minimising the likelihood of such complications. The most common pharmacokinetic interactions are caused by an inhibitory effect of the SSRIs on the hepatic cytochrome P450 (CYP) metabolic system. The SSRIs differ in their potency in inhibiting a number of important CYP isoenzymes (CYP1A2, CYP2C9/10, CYP2C19, CYP2D6 and CYP3A3/4). The major outcome of concern in relation to pharmacodynamic interactions is the development of the 'serotonin syndrome'. While combination of the SSRIs with the irreversible monoamine oxidase inhibitors is the most recognised cause of this syndrome, concurrent administration with moclobemide, tryptophan or selegiline (deprenyl) may also lead to a similar outcome.
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Safety of selegiline (deprenyl) in the treatment of Parkinson's disease.

Heinonen EH, Myllyla V.

Orion Pharma, CNS Drugs, Turku, Finland.

Selegiline (deprenyl), a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) is widely used in the treatment of Parkinson's disease. As the first MAO-B inhibitor approved for the treatment of Parkinson's disease, concerns were raised about the safety of the drug based on the adverse effect profiles of older, nonselective MAO inhibitors. Unlike the nonselective MAO inhibitors, selegiline does not significantly potentiate tyramine-induced hypertension (the 'cheese effect') at the dosages (5 to 10 mg daily) used for the treatment of Parkinson's disease. Selegiline has been well tolerated when given alone. The most frequent adverse events seen during monotherapy have been insomnia, nausea, benign cardiac arrhythmias, dizziness and headache. When combined with levodopa, selegiline can potentiate the typical adverse effects of levodopa, if the dose of levodopa is not reduced sufficiently. Thus, the most common adverse effects associated with this combination are nausea, dizziness, fatigue, constipation and insomnia. At the later stages of Parkinson's disease when fluctuations in disability occur, peak dose dyskinesias, psychiatric complications like hallucinations and insomnia, and orthostatic hypotension are further potentiated by selegiline. Mortality was recently reported to be increased when selegiline and levodopa were given together in comparison with treatment with levodopa alone, but a large meta-analysis of 5 long term studies and 4 separate studies did not support this conclusion. Selegiline seems to be generally well tolerated in combination with other drugs. However, when pethidine (meperidine) has been given to patients who are receiving selegiline therapy, severe adverse effects have been reported. Thus, the concomitant use of these drugs is not recommended. A low tyramine diet is recommended if selegiline is used together with nonselective MAO inhibitors or the selective, reversible MAO-A inhibitor, moclobemide. Several adverse effects have been reported when fluoxetine and selegiline have been used together. A recent survey revealed that the incidence of a true serotonin syndrome is, however, very low with this combination. Concomitant use of selegiline and other selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) like citalopram, which have generally less interactions than fluoxetine, seems to be well tolerated. Nevertheless, caution is advised when combining a SSRI or a tricyclic antidepressant and selegiline.
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Retrospective study of selegiline-antidepressant drug interactions and a review of the literature.
Ritter JL, Alexander B.
University of Washington Medical Center, Seattle 98105, USA.

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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Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group.
Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, Waters C.
University of Rochester Medical Center, Department of Neurology, NY 14642-8673, USA.

The manufacturer of deprenyl (selegeline; Eldepryl) (Somerset Pharmaceuticals, Tampa, FL) recently advised physicians to avoid prescribing the drug in combination with an antidepressant because of potentially serious CNS toxicity that may represent the serotonin syndrome. Manifestations of the serotonin syndrome vary but may include changes in mental status and motor and autonomic function. To better estimate the frequency of the serotonin syndrome in patients with Parkinson's disease (PD) treated with deprenyl and an antidepressant, we surveyed all investigators in the Parkinson Study Group. Based on estimates provided by the 47 investigators (75%) who responded, 4,568 patients were treated with the combination of deprenyl and an antidepressant medication. Eleven patients (0.24%) were reported to have experienced symptoms possibly consistent with the serotonin syndrome. Only two patients (0.04%) experienced symptoms considered to be serious. No deaths were reported. We also reviewed all published case reports and adverse experiences reported to the U.S. Food and Drug Administration and the manufacturer of Eldepryl. Available information indicates that serious adverse experiences resulting from the combined use of deprenyl and an antidepressant medication in patients with PD are quite rare and that the frequency of the true "serotonin syndrome" is even rarer.


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poster:wingedcat thread:138787
URL: http://www.dr-bob.org/babble/20030130/msgs/139133.html