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selegiline and SSRIs


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#1 ~ prometheus ~

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Posted 04 October 2006 - 01:23 AM


if selegiline is a selective MAO-B inhibitor, and serotonin is preferentially deaminated by MAO-A, one would assume that concomitant usage of SSRIs and selegiline wouldn't cause serotonin syndrome.

i'm on 20 mg paroxetine. last night i took 5 mg of liquid selegiline. after taking my dose, i decided to read up more on selegiline, only to find that this combination can cause serotonin syndrome. i contacted the poisons information centre and they told me to go to hospital. i stayed overnight for observation but nothing eventful happened. no nasty serotonin syndrome, though the doctors told me a reaction would be highly probable. i felt quite foolish for fucking up like that, but i'm glad i swallowed my pride and stayed overnight.

does anyone have any experience combining selegiline with SSRIs? i'd prefer to take the two, but may have to ditch the paroxetine if i want to give selegiline a go.

mental note: read up on contraindications BEFORE taking a new drug... :)

#2 dopamine

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Posted 04 October 2006 - 03:41 AM

SSRI + MAOI is a textbook interaction, but low dose Selegiline (5-10 mg) isn't like Parnate or Phenelzine, which are unselective for A and B type substrates. There has been some research into the area:

   
Eur J Pharmacol. 2006 Feb 27;532(3):258-64.

Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo 060-8638, Japan. psyizumi@med.hokudai.ac.jp

5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.

PMID: 16488409


This would appear to suggest that, at least in rats, Selegiline is not conducive to serotonin syndrome, within the context of this particular experimental paradigm.

There is a case report of death associated with serotonin syndrome, caused by the combination of selegiline and fluoxetine, though the doses are not given in the abstract:

Rev Clin Esp. 2002 Apr;202(4):209-11.Click here to read

[Serotonin syndrome: report of a fatal case and review of the literature]

[Article in Spanish]

Servicio de Medicina Interna, Fundacion Hospital Alcorcon, Madrid, Spain. jbilbao@fhalcorcon.es

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.

PMID: 12003730


A review of Parkinson's patients who take Selegiline with antidepressants was also published, an important reference for inquiry concerning the combination:

Neurology. 1997 Apr;48(4):1070-7.

Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group.

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.

PMID: 9109902


The abstract doesnt say what type of antidepressants were used (e.g. tricyclics, 5HT agonists, NRI's) but SSRI's are the most popular and most likely to be chosen by clinicians as "first line" treatment.

Finally, there was a study done looking at the safety of combining selegiline with citalopram (more commonly referred to as "Celexa"), a popular SSRI, showing no serious interaction:

Clin Neuropharmacol. 1997 Oct;20(5):419-33.

Lack of adverse interactions between concomitantly administered selegiline and citalopram.

Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.

We have evaluated the risk for pharmacokinetic and/or pharmacodynamic interactions of concomitantly administered selegiline, a selective monoamine oxidase type B inhibitor, and citalopram, a widely used selective serotonin uptake inhibitor antidepressant. Two parallel groups of healthy volunteers received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 days in a randomized, double-blind fashion, followed by concomitant selegiline 10 mg once daily for 4 days. The safety of this drug combination was assessed by measurements of blood pressure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of both study drugs and their metabolites and plasma prolactin, adrenaline, noradrenaline, and 3,4-dihydroxyphenylglycol (DHPG); urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were assessed. After a 5-week washout, the 12 subjects who took citalopram in the first part of the study received 10 mg of selegiline once daily for 4 days to compare the pharmacokinetics of selegiline with and without concomitant citalopram. The safety analysis showed no significant differences in vital signs or the frequency of adverse events between the study groups. Plasma prolactin concentrations were increased by 40% after 10 days' treatment with citalopram (p = 0.03); this was not potentiated by concomitantly administered selegiline. The comparison of plasma concentrations of noradrenaline, adrenaline, and DHPG and the amount of serotonin and 5-HIAA excreted into urine between the study groups indicated no signs of subclinical pharmacodynamic interaction between selegiline and citalopram. The relative bioavailability of selegiline was slightly reduced (by 29%; p = 0.008) when citalopram was coadministered compared with selegiline alone. However, no indication of a pharmacokinetic interaction was found in the analysis of serum concentrations of the three main metabolites of selegiline. The pharmacokinetics of citalopram remained unaffected by concomitant selegiline. The present results indicate lack of clinically relevant pharmacodynamic or pharmacokinetic interactions between selegiline and citalopram.

PMID: 9331518


This study was conducted only over a 10 day period, and mainly looked at pharmacodynamic interactions, but is instructive nonetheless.

The combination is probably not a good idea in general, but the majority of the data seem to indicate that MAO-B selective doses of selegiline is safe when combined with most SSRI's.

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#3 ~ prometheus ~

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Posted 04 October 2006 - 09:10 AM

thanks for the response dopamine. i had a read of that study on serotonin syndrome in parkinson's patients. seems like there's little evidence of a negative interaction, though obviously one should maintain dosing at levels below 10 mg/day.

just a note though, selegiline seems to lose its MAO-B selectivity after prolonged use:


Deprenil: loss of selectivity for inhibition of B-type MAO after repeated treatment.
PC Waldmeier, AE Felner - Biochem Pharmacol, 1978


...These results demonstrate that in the rat, the selectivity
for inhibition of MAO B (PEA deamination) observed after
acute treatment with the irreversible MAO, inhibitor
deprenil diminishes progressively in the course of repeated
treatment, as MAO A (5-HT deamination) becomes more
and more effectively inhibited compared to MAO B, which
is initially much more strongly inhibited. This effect seems
to be more pronounced in the brain than in the liver, probably
owing to the lower rate of enzyme resynthesis in cerebral
tissue.

#4 dopamine

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Posted 04 October 2006 - 05:10 PM

That is one thing to worry about with selegiline, i.e. that over extended periods of time, inhibiting MAO-B irreversibly will cause a "spill over" effect to the other substrate.

As for personal experiences, I have combined different SSRI's with selegiline short term, including paroxetine, sertraline and escitalopram. The doses have never been over 5 mg. The only time I can think that I may have a serotonin-syndrome type reaction was when I ignorantly combined 30 mg of paroxetine with 100 mg of 5-HTP. So your not alone, we all make stupid mistakes. All we can do is learn from them and (hopefully) survive.

#5 zoolander

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Posted 04 October 2006 - 08:25 PM

From what I have read, taking 100mg of 5-HTP per night before bed and low dose deprenyl (i.e 1mg x 4-5 days /wk) should not result in serotonin syndrome.

agreed or disagreed people?

Who is taking both at the moment? Put up your hands

o/

#6 ~ prometheus ~

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Posted 05 October 2006 - 04:12 AM

zoolander, 1 mg is a pretty low dose. in rats given 0.2 mg/kg s.c., MAO-A is inhibited by only 6% to MAO-B's 85%. in theory you'd be fine, in practise... well, just remember murphy's law :)

combining selegiline with serotoninergic drugs seems ok. i'm now taking selegiline with my paroxetine with no side-effects. though granted, i haven't had the guts to take my paroxetine for 2 days, though i can rationally tell myself that it is most likely safe to do so.

#7 Guest_da_sense_*

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Posted 08 October 2006 - 09:35 PM

Don't play with MAOIs!
I've taken 5 mg Selegiline for one year. One day I've added some other drugs (tramadol, ephedrine...) and experienced worst day in my life. I though i was going to die. Luckily i was sober enough to search for the info on the web (though my vision was blurry) and found that there is no cure, but lorazepam is often given in such state to help in recovery. Lorazepam is the only benzodiazepine i ever had, so i took 1mg and went to sleep. 2 hours later i woke up good as new.
Point is, while low doses of selegiline (5mg daily) are usually not dangerous in combination with some other drugs can lead to serotonin syndrome.

#8 evodude

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Posted 15 September 2011 - 03:35 AM

zoolander, 1 mg is a pretty low dose. in rats given 0.2 mg/kg s.c., MAO-A is inhibited by only 6% to MAO-B's 85%. in theory you'd be fine, in practise... well, just remember murphy's law :)

combining selegiline with serotoninergic drugs seems ok. i'm now taking selegiline with my paroxetine with no side-effects. though granted, i haven't had the guts to take my paroxetine for 2 days, though i can rationally tell myself that it is most likely safe to do so.



Interesting, what was the dose?

#9 Dirk_Diggler

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Posted 15 September 2011 - 04:10 AM

Well it's been 5 years...OLD thread...

#10 Boolean

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Posted 15 September 2011 - 07:30 PM

The bane of the search function. It's still a VALID question... I take 5-htp and tryptophan before bed, but have forgone this while on Selegiline. I'm about to go get myself some, and lower my dosage of Selegiline to 3mg 2x daily. Let's see what happens! WEEE!

#11 evodude

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Posted 03 October 2011 - 07:41 PM

I found this on a medical paper. They did a research of 4500 people with this combination. 11 patients (0.24%) had symptons that might fit with serotoninesyndrome. Two patients(0,04%) experienced serious symptoms. From the 57 notifications at the FDA about interactions as result of combining selegiline and a anti depressant 27 where treated with a TCA , 27 with an SSRI, one with venlafaxine and two with trazodon. 3 fatal complications where reported: with 2 of these amitriptyline was used and with one protriptyline. But also the combination of SSRI with selegiline are serotoninesyndrom with fatal ending. serotoninesyndromen are described with combinations as selegiline and fluoxetine, selegiline and nortriptyline, and levodopa and a SSRI
  • Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Neurology 1997; 48: 1070-1077.
  • Bilbao Garay J, Mesa Plaza N, Castilla Castellano V, Dhimes Tejada P. Serotonin syndrome: report of a fatal case and review of the literature. Rev Clin Esp 2002; 202: 209-211.
  • Hinds NP, Hillier CE, Wiles CM. Possible serotonin syndrome arising from an interaction between nortriptyline and selegiline in a lady with parkinsonism. J Neurol 2000; 247: 811.
  • Ritter JL, Alexander B. Retrospective study of selegiline-antidepressant drug interactions and a review of the literature. Ann Clin Psychiatry 1997; 9: 7-13.

Edited by evodude, 03 October 2011 - 07:45 PM.


#12 parsons

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Posted 06 April 2012 - 06:39 PM

The bane of the search function. It's still a VALID question... I take 5-htp and tryptophan before bed, but have forgone this while on Selegiline. I'm about to go get myself some, and lower my dosage of Selegiline to 3mg 2x daily. Let's see what happens! WEEE!

so what happened? I've just order some selegiline and am a user of 5-htp. I take 200-400 mgs of 5-htp so i'm interested

#13 parsons

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Posted 06 April 2012 - 09:23 PM

The bane of the search function. It's still a VALID question... I take 5-htp and tryptophan before bed, but have forgone this while on Selegiline. I'm about to go get myself some, and lower my dosage of Selegiline to 3mg 2x daily. Let's see what happens! WEEE!

so what happened? I've just order some selegiline and am a user of 5-htp. I take 200-400 mgs of 5-htp so i'm interested

perhaps with 5-htp, it could be good news
http://www.antiaging...rticle_4_1.html
"In 1978, Mendelwicz and Youdim treated 14 depressed patients with 5 mg deprenyl plus 300 mg 5-HTP three times daily for 32 days. Deprenyl potentiated the antidepressant effect of 5-HTP in 10 of the 14 patients. 5-HTP enhances brain serotonin metabolism, which is frequently a problem in depression, while deprenyl enhances the dopamine/ noradrenaline activity. Under-activity of brain dopamine, noradrenaline and serotonin neural systems are the most frequently cited biochemical causes of depression, so deprenyl plus 5-HTP would seem a natural antidepressant combination."

#14 Boolean

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Posted 17 April 2012 - 03:50 PM

The bane of the search function. It's still a VALID question... I take 5-htp and tryptophan before bed, but have forgone this while on Selegiline. I'm about to go get myself some, and lower my dosage of Selegiline to 3mg 2x daily. Let's see what happens! WEEE!

so what happened? I've just order some selegiline and am a user of 5-htp. I take 200-400 mgs of 5-htp so i'm interested


What happened? I ran out of Selegeline before I started my course of 5-htp and l-tryptophan. I've failed you all. =(

#15 FreeMind

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Posted 01 October 2013 - 06:33 AM

Daily 5mg selegiline and an SSRI is safe and very effective from my experience. I experienced this many times.

Just do not mix selegiline with something else (PEA,Ephedrine, etc..).

#16 jaiho

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Posted 16 July 2014 - 07:54 AM

what about 5mg Selegiline with 20-40mg Fluoxetine? There's a death mentioned there..



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#17 crazepharmacist

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Posted 18 May 2015 - 01:55 PM

Is 5 or 2.5 mg of selegiline per week a safe combination with daily Prozac use? 


Edited by crazepharmacist, 18 May 2015 - 01:55 PM.





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