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.
