Guest guest Posted January 23, 2000 Report Share Posted January 23, 2000 I have been following the discussion of possible drug-drug interactions of simultaneous administration of Selegline (Deprenyl) and fluoxetine (Prozac)with some interest and would like to contribute my $0.02 worth to this thread. I added Prozac to my present regimen of polypharmacy about 2 months ago (doctor's prescription)and as part of that same regimen I use approximately 1.25-2.5 mg Selegline (no prescription) every 1-2 days. (As an aside, I occassionally at bedtime use L-Dopa/(Carbidopa) (250mg(25mg)-500mg(50mg) for GH release and more frequently GHB (4g. at bedtime)no prescriptions here either). This discussion drove me to consult one of my favourite texts, PRINCIPLES OF PHARMOCOLOGY,Ed. P.L.Munson, Chapman & Hall, 1995. From Chapt. 18, p.333, I quote: " Because Deprenyl is selective for MAO-B, it inhibits the oxidation of dopamine and phenylethylamine (PEA) but not that of serotonin or norepinepherine. " Unless there is some substantial hard evidence to the contrary, I presume that 'Serotonin Syndrome'is probably not a consideration. However, what other polypharmacists (and devil-may-care characters such as myself) might want to consider is the posibility of unusually high levels of dopamine created by self-administration of similiar regimens to that above. I would be very interested on other people's views here. Regards, A. Re: deprenyl Serotonin syndrome is an unpleasant and sometimes dangerous condition that arises from having too much serotonin in the brain. It can cause dizziness, panic, and hyperthermia. Serotonin is a neurotransmitter and a hormone. Drugs like fluoxetine (Prozac) are SSRI's (Selective Serotonin Reuptake Inhibitors). SSRI's fight depression by preventing the brain cells from reuptaking serotonin. St 's Wort seems to work by increasing serotonin and/or inhibiting MAO, though not much is known yet about St 's Wort. I don't understand the mechanism by which selegiline (Deprenyl) might also increase serotonin, but in theory the combination of any serotonin-increasing drug or herb with deprenyl could result in serotonin syndrome. There could be some risk to taking 5-HTP with deprenyl as well, I think, because 5-HTP is the direct precursor to serotonin. I've also seen that one researcher has proposed that deprenyl should be okay to use with citalopram (Celexa), which is another SSRI. I have no idea why one SSRI might be okay but another not okay. Here is a page of links to research abstracts at my website: http://www.optexinc.com/deprenyl.htm -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 23, 2000 Report Share Posted January 23, 2000 Hi , > Unless there is some substantial hard evidence to the contrary, I presume > that 'Serotonin Syndrome'is probably not a consideration. I agree that selegiline and fluoxetine (Deprenyl and Prozac) should be safe in theory but apparently there have been a few problems with the combination. I have included two research abstracts below. The first one that states " selegiline (deprenyl) is free of the 'cheese-effect' when employed in recommended dosages. However potentially life-threatening drug interactions, with both pethidine (meperidine) and with fluoxetine [Prozac] and other antidepressant medications, have been described, presumably occurring via serotonergic mechanisms " . However the second research abstract states that no significant interations were found in a population of patients that took both fluoxetine and selegiline. -gts --- Title Antiparkinsonian agents. Drug interactions of clinical significance. Author Pfeiffer RF Address Division of Neurodegenerative Diseases, University of Tennessee, Memphis, USA. Source Drug Saf, 14(5):343-54 1996 May Abstract Within the past 3 decades revolutionary changes have taken place in the pharmacological management of Parkinson's disease. Used alone, or often in combination, antiparkinsonian agents can dramatically and meaningfully ameliorate the symptoms of Parkinson's disease. However, with the development of effective therapeutic agents has come the potential for drug interactions; these interactions can produce consequences that range from the inconsequential to incapacitating and even life-threatening. Drug-drug interactions are not a major problem with either the anticholinergic medications or amantadine. However, cumulative anticholinergic toxicity may occur when multiple drugs with anticholinergic properties are utilised concomitantly, and amantadine toxicity can be triggered by drugs that impair its renal clearance. Gastric emptying and levodopa absorption can be significantly altered by medications and dietary contents. A rather extensive array of medications can interfere with dopaminergic function and thus produce clinical parkinsonism or impair the effectiveness of levodopa. The effectiveness of direct dopamine agonists can also be affected by a small group of agents. As a selective monoamine oxidase type B (MAO- inhibitor, selegiline (deprenyl) is free of the 'cheese-effect' when employed in recommended dosages. However, potentially life-threatening drug interactions, with both pethidine (meperidine) and with fluoxetine and other antidepressant medications, have been described, presumably occurring via serotonergic mechanisms. Awareness of the potential for drug interactions with antiparkinsonian agents, and prompt recognition of them when they do occur, is vital for the optimum clinical management of Parkinson's disease. Language Eng Unique Identifier 96393965 Title Fluoxetine and selegiline--lack of significant interaction. Author Waters CH Address Department of Neurology, University of Southern California, Los Angeles 90033. Source Can J Neurol Sci, 21(3):259-61 1994 Aug Abstract The use of the combination of fluoxetine, an anti-depressant serotonin uptake inhibitor, and selegiline, a monoamine oxidase -B inhibitor, was reviewed in a large population of patients with Parkinson's disease. All records were reviewed from a Parkinson's disease clinic to determine how many patients were treated simultaneously with selegiline and fluoxetine. Patient characteristics, duration and dose of treatment, side effects and reasons for discontinuation were noted. Twenty-three patients received both medications at the same time. No additional side effects were noted with the combination therapy that had not already been reported with each medication alone. No serious side effects were found. In this clinic population, fluoxetine and selegiline were used in combination without major side effects, but further observation is warranted. Language Eng Unique Identifier 95094107 Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 24, 2000 Report Share Posted January 24, 2000 Hello Gordon: Thank you for these two article summaries. Hmmm, sounds a bit worrisome...however, from the first abstract we can't tell what the dosage levels were in the 'described' cases...but I suspect that if the groups under consideration were only taking standard therapeutic doses (ie 20-30mg Prozac and 10mg. or less of Deprenyl) there may be something to worry about. But, from this particular article abstract...I wouldn't 'presume' so. As a matter of fact, whether or not the cheese-effect is exhibited with Deprenyl is directly relational to dosage. Above 10mg, you may actually get the cheese-effect...above 20mg you certainly will. Best, A. Re: (gts) deprenyl Hi , > Unless there is some substantial hard evidence to the contrary, I presume > that 'Serotonin Syndrome'is probably not a consideration. I agree that selegiline and fluoxetine (Deprenyl and Prozac) should be safe in theory but apparently there have been a few problems with the combination. I have included two research abstracts below. The first one that states " selegiline (deprenyl) is free of the 'cheese-effect' when employed in recommended dosages. However potentially life-threatening drug interactions, with both pethidine (meperidine) and with fluoxetine [Prozac] and other antidepressant medications, have been described, presumably occurring via serotonergic mechanisms " . However the second research abstract states that no significant interations were found in a population of patients that took both fluoxetine and selegiline. -gts --- Title Antiparkinsonian agents. Drug interactions of clinical significance. Author Pfeiffer RF Address Division of Neurodegenerative Diseases, University of Tennessee, Memphis, USA. Source Drug Saf, 14(5):343-54 1996 May Abstract Within the past 3 decades revolutionary changes have taken place in the pharmacological management of Parkinson's disease. Used alone, or often in combination, antiparkinsonian agents can dramatically and meaningfully ameliorate the symptoms of Parkinson's disease. However, with the development of effective therapeutic agents has come the potential for drug interactions; these interactions can produce consequences that range from the inconsequential to incapacitating and even life-threatening. Drug-drug interactions are not a major problem with either the anticholinergic medications or amantadine. However, cumulative anticholinergic toxicity may occur when multiple drugs with anticholinergic properties are utilised concomitantly, and amantadine toxicity can be triggered by drugs that impair its renal clearance. Gastric emptying and levodopa absorption can be significantly altered by medications and dietary contents. A rather extensive array of medications can interfere with dopaminergic function and thus produce clinical parkinsonism or impair the effectiveness of levodopa. The effectiveness of direct dopamine agonists can also be affected by a small group of agents. As a selective monoamine oxidase type B (MAO- inhibitor, selegiline (deprenyl) is free of the 'cheese-effect' when employed in recommended dosages. However, potentially life-threatening drug interactions, with both pethidine (meperidine) and with fluoxetine and other antidepressant medications, have been described, presumably occurring via serotonergic mechanisms. Awareness of the potential for drug interactions with antiparkinsonian agents, and prompt recognition of them when they do occur, is vital for the optimum clinical management of Parkinson's disease. Language Eng Unique Identifier 96393965 Title Fluoxetine and selegiline--lack of significant interaction. Author Waters CH Address Department of Neurology, University of Southern California, Los Angeles 90033. Source Can J Neurol Sci, 21(3):259-61 1994 Aug Abstract The use of the combination of fluoxetine, an anti-depressant serotonin uptake inhibitor, and selegiline, a monoamine oxidase -B inhibitor, was reviewed in a large population of patients with Parkinson's disease. All records were reviewed from a Parkinson's disease clinic to determine how many patients were treated simultaneously with selegiline and fluoxetine. Patient characteristics, duration and dose of treatment, side effects and reasons for discontinuation were noted. Twenty-three patients received both medications at the same time. No additional side effects were noted with the combination therapy that had not already been reported with each medication alone. No serious side effects were found. In this clinic population, fluoxetine and selegiline were used in combination without major side effects, but further observation is warranted. Language Eng Unique Identifier 95094107 ------------------------------------------------------------------------ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 26, 2000 Report Share Posted January 26, 2000 As I understand it, the cheese effect is typical only in high doses of Deprenyl. Is this correct? If 5 mg was taken once or twice a week, one would not need to worry about this effect; true? Thanks for the clarification (in advance). ______________________________________________________ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 26, 2000 Report Share Posted January 26, 2000 Dear , I missed it what is the 'cheese effect'? --Glenn Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 26, 2000 Report Share Posted January 26, 2000 Hi Glenn, The term 'cheese effect' describes a potentially fatal interaction of MAOs with certain tyramine containing foods (most notably cheese, beer,nuts, etc.)resulting in a rather lethal rise in blood pressure. Regards, A. Dear , I missed it what is the 'cheese effect'? --Glenn ------------------------------------------------------------------------ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 26, 2000 Report Share Posted January 26, 2000 > As I understand it, the cheese effect is typical only in high doses of > Deprenyl. Is this correct? If 5 mg was taken once or twice a week, one would > not need to worry about this effect; true? Thanks for the clarification (in > advance). Yes that is my understanding also. I believe the cheese effect is a problem only with MAO-A inhibitors. At low doses selegiline (deprenyl) is only a MAO-B inhibitor. At high doses, of approximately 10 mg/day and higher, selegiline becomes a MAO-A inhibitor as well. The question that concerns me and is that of serotonin syndrome, which is separate and distinct from the cheese effect. Apparently MAO inhibitors slow the metabolism of serotonin, and so combining them with serotonin reuptake inhibitors like Prozac can result in an excess of serotonin in the synapses, which can be dangerous. I'm not certain at what doses the problem becomes significant. Here is a link to an excellent article about serotonin syndrome. It mentions deprenyl. http://www.uspharmacist.com/NewLook/DisplayArticle.cfm?item_num=94 -gts Quote Link to comment Share on other sites More sharing options...
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