!

MENU

Search

SEROTONIN TOXICITY MENU !

Monoamine Oxidase Inhibitors, Opiate

Analgesics and Serotonin Toxicity
by Dr Ken Gillman | Last updated Mar 24, 2019 | Published on Nov 13, 0204 |

Serotonin Toxicity, Anti-Depressants

Summary
The serotonin reuptake inhibitor potency of most of the
commonly used opioid analgesics is now known from quality in
vitro data. This data is entirely consonant with my previous
interpretation concerning which of these drugs were, or were
not, capable of precipitating serotonin toxicity. The most
important substantiation of my predictions made from the
spectrum concept of serotonin toxicity concerns the widely used
drug fentanyl, and its congeners. Fentanyl is now established to
have no significant serotonin reuptake inhibitor potency and it
can be concluded that it poses no risk of serotonin toxicity when
mixed with MAO inhibitors (or any other ‘serotonergic’ drugs).
:
 Introduction
Note: Much of the data in the old commentary, which is retained
here below this update, was published in my review in the
British J. Anaesthesia (1).

The situation with opioid analgesics is now clear and this March
2015 updating of this commentary has been precipitated by
recent research (2, 3) which contains useful new data concerning
the in vitro SRI potency of opioids, including fentanyl*. This
data allows a considerable contraction of some of the detailed
interpretation in my previous summary of this subject. I have
inserted this new more concise note in front of the old
commentary which I have preserved for historical interest, and
for the interest of that proportion of researchers who may wish
to have access to it.

It is useful to begin by noting that the spectrum concept of

serotonin toxicity has yet again yielded reliable predictions of
which drugs do and do not have significant serotonin reuptake
inhibition actions from their propensity to provoke ST when
combined with MAOIs. This is especially relevant and
important in view of the epidemic of unnecessary warnings
issued by various government agencies in the Western world
concerning a whole raft of drugs including triptans, 5-HT3
antagonists and many others. These erroneous warnings are
based on case reports and even less satisfactory reports to drug
monitoring agencies. My universal experience in assessing such
data (in the context of serotonin toxicity) is that it is almost
always of negligible value and has repeatedly lead to mistaken
conclusions and actions.

It is therefore especially gratifying to report another successful

prediction of the spectrum concept of serotonin toxicity
concerning fentanyl and its congeners.
:
 The Current Situation

Members of the phenylpiperidine series of opioids have long

been known or suspected to posses SRI potency of possibly
sufficient degree to give risk of ST (viz. pethidine (meperidine),
methadone and fentanyl, and d-propoxyphene) and also
tramadol.

My previous commentary and published comments explained

that the phenanthrene series (morphine etc.) were known to be
safe (i.e. they have no SRI activity) whereas tramadol and
pethidine (meperidine) appeared to carry a significant ST risk,
but fentanil was probably safe.

The classes of opioids are; phenanthrenes: Morphine,

Hydromorphone, Oxymorphone, Levorphanol, Codeine,
Hydrocodone, Oxycodone, Buprenorphine, Butorphanol,
Nalbuphine, Pentazocine, Dezocine;

phenylheptylamines: Methadone, Propoxyphene,

Levomethadyl;

phenylpiperidines: Fentanyl, sufentanyl, Meperidine aka

pethidine.

Tramadol is a weak atypical opioid (4-phenyl-piperidine

analogue of codeine and structurally very similar to venlafaxine
and with a similar toxicity profile).

We now have a good indication from in vitro data produced by

Barann, Stamer et al. (2) of the relative SRI potency of
tramadol,pethidine (meperidine), fentanyl, alfentanil, morphine
and hydromorphone. Tramadol is the most potent SRI which is
in keeping with its seemingly greater potential to induce ST,
followed by pethidine (meperidine). The others fentanyl,
:
 alfentanil, morphine and hydromorphone have no SRI potency.

Until now the main drug of clinical relevance about which there
was significant uncertainty was fentanyl. I have previously
argued that it is almost certainly not associated with reports of
serotonin toxicity and has frequently been used in conjunction
with MAOIs without any signs of toxicity (see discussion of this
in relation to MB), thereby proving it has negligible SRI potency
(4, 5). That view is firmly supported by this new data.

This new data and analysis enables clinicians to be even more

confident when making decisions about patient management.
The degree of risk with known serotonergic opioids like
meperidine is relatively low (see details in old commentary
below), but it is not precisely predictable and the potentially
fatal outcome of ST suggests that in usual circumstances it
would be prudent to avoid serotonergic opioids in patients who
have been taking MAOIs (like tranylcypromine and phenelzine
etc see link) and to use the drugs known not to be SRIs where
possible.

*Reminder: quite a lot of drugs have alternative spellings,

usually for no good reason. In this particular instance fentanyl is
usually spelt with a ‘y’ whereas sufentanyl is usually spelt with
an ‘i’, but one encounters variations of both.

References

1.Gillman, PK, Monoamine oxidase inhibitors, opioid analgesics

and serotonin toxicity. Br. J. Anaesth., 2005. 95: p. 434-441.

2.Barann, M, Stamer, UM, Lyutenska, M, Stuber, F, et al.,

Effects of opioids on human serotonin transporters. Naunyn.
Schmiedebergs Arch. Pharmacol., 2015. 388(1): p. 43-9.

3.Barann, M, Urban, B, Stamer, U, Dorner, Z, et al., Effects of

:
 tramadol and O-demethyl-tramadol on human 5-HT reuptake
carriers and human 5-HT3A receptors: a possible mechanism for
tramadol-induced early emesis. Eur J Pharmacol, 2006. 531(1-
3): p. 54-8.

4.Gillman, PK, Fentanyl and serotonin toxicity. Br. J.

Anaesth., 2009:
p. http://bja.oxfordjournals.org/cgi/eletters/95/4/434#4135.

5.Gillman, PK, Meperidine (pethidine) and toxicity. Br. J.

Anaesth., 2010:
p. http://bja.oxfordjournals.org/content/103/3/369.abstract/reply.

Previous Commentary

Note: Much of the data below has now been published in my

review in the BJA (1).

The very first cases of serotonin toxicity occurred when patients

were given the early anti-tuberculous drugs. Mitchells report,
which is the first ever case in a human, was an interaction
between iproniazid and pethidine. Some of the other early cases
referenced below were precipitated by the use of pethidine in
patients being treated with iproniazid for angina. The physicians
looking after these patients were aware of, and cited, the earlier
reports, documented herein, where chlorpromazine had been
successfully employed to lessen such reactions, and the earliest
reports of successful use of chlorpromazine in humans were in
these patients. Some of these were reported by anaesthetists and
occurred in patients having operative procedures like
leucotomies. As a result of the uncertainty in this area Churchill-
Davidson (2) developed a testing procedure for checking
whether patients on MAOIs were likely to exhibit a reaction to
:
 analgesics. Evans-Prosser (3) modified this procedure in 1968
and described an experiment in which they gave 15 patients
injections of pethidine or morphine or water, in graduated doses,
under controlled conditions in hospital. The total dose of
pethidine was 75 mg and of morphine 7.5 mg. Each of the 15
patients received in blind order each of these three treatments.
No reactions suggestive of serotonin toxicity were observed. It
may be noted that although the patients were observed carefully
these experimenters clearly did not know what symptoms of
serotonin toxicity to look for and only measured the blood
pressure and heart rate. No significant changes were noted.
However, they were carefully observed, and the expected
reaction of shivering, agitation, clonus and hyperreflexia would
have been very obvious, and may reliably be presumed not to
have occurred. This group of patients represents the only case
series of this sort, and even now it is valuable data. It
demonstrates clearly what the spectrum concept of serotonin
toxicity predicts, which is that weak serotonergic opioids like
pethidine are capable of precipitating serotonin toxicity, but this
is only likely with susceptible individuals, or with particularly
large doses.

All the references I have located, through a search of the listed

papers and standard databases, are listed under the relevant
headings below. Pethidine has undoubtedly caused a number of
reactions which have been severe, with some fatalities; the other
serotonergic opioids should be expected to precipitate fatalities
in similar circumstances. The more recent fatalities are: (4-8).
See also Gillman (9) for further comment on older cases.

Especially when taken in conjunction with the Evans Prosser

paper above, this is a clear illustration of how a small case series
using limited doses may lead to a false sense of security, because
the dose-effect relationship is not sufficiently appreciated. This
:
 is especially important when phamacokinetic and
pharmacodynamic interactions coincide (cf moclobemide and
Dingemanses papers).

The limited available clinical and experimental data agree that

morphine analogues are not serotonin reuptake inhibitors (or
releasers), nor do any of them precipitate serotonin toxicity with
monoamine oxidase inhibitors (viz.: Morphine, Codeine,
oxycodone, buprenorphine). There are no reliable reports of
serotonin toxicity with those drugs (see table 7).

The phenylpiperidine series opioids, pethidine (meperidine),

tramadol, methadone and fentanyl, and d-propoxyphene, are all
borderline, being very weak serotonin and re-uptake inhibitors
(table 7). These drugs have been involved in multiple reports
which are almost certainly serotonin toxicity, as judged by a
subjective interpretation of the old case reports, informed by
more accurate recent data concerning the characteristic features
of serotonin toxicity. More precise data from human cloned
receptor assays would be valuable because we can reliably
predict that only those drugs that are significant serotonin
reuptake inhibitors (or releasers) will precipitate serotonin
toxicity.

We can reliably predict that only those opiates that are

significant serotonin reuptake inhibitors (or releasers) will
precipitate serotonin toxicity with MAOIs. Human cloned
receptor data 5-HT transporter affinity of narcotic analgesics
(antidepressants for comparison) from (10).

ST reports
DRUG Ki nM with
MAOIs

Other refs Codd

:
 Definite,
0.13 – 2.2 and
All SSRIs
potent frequent
fatalities

Definite,
and
Clomipramine 0.14 potent
frequent
fatalities

Definite,
Imipramine 1.3 and some
fatalities

None, no
Amitriptyline 2.8-36 weak
fatalities

Definite,
and
7.5-102
Venlafaxine fatalities
anomalous*
(>
SSRIs?)

Morphine 500,000 >100,000 None

Codeine – >100,000 None

Buprenorphine – >100,000 None

Oxycodone – >100,000 None

Definite,
and
Tramadol 760-1820*** 528
possible
fatalities

Dextromethorphan – 23 Definite

d-propoxyphene 30,000 ??? see

:
 refs

Definite,
413 weak,
Pethidine – and some
anomalous**
fatalities

No
Pentazocine – – reports
known

Uncertain.
One case
of ST, and
Fentanil – – one
possible
death
reported

No case
Remifentanil – – or death
reported

No
reports
Methadone 270 14.1 known,
but
possible

Table notes:– In vitro receptor assays give an estimate of the

drugs potency as an SRI; a lower Ki indicates higher potency.
Until replicated human cloned receptor data is available for all
of these drugs no precise comparisons will be possible. It is
important to note that this data can only give a guide as to
potency. The results from Codd are presented separately because
this is the only paper that has screened a group of drugs using
the same methodology.
:
 *venlafaxine, may have other serotonergic action as well as
serotonin reuptake inhibitor potency: this might be related to the
anomalous toxicity, it is weaker as an SRI than at any other
antidepressant that is capable of inducing ST. There is also
evidence that tramadol, like the close structural homologue
venlafaxine, may have some other serotonergic action as well as
weak serotonin reuptake inhibitor potency (11-14).

** More recent data (15).

*** More recent SRI data re tramadol (16,17). As a single 100

mg dose of tramadol produces peak plasma concentrations of
300 ng/ml, equivalent to about 1 µM conc. that suggests
tramadol might have some effect on serotonin transporter
(SERT).

Codd​s paper
Codds paper is the only one (that I know of) that examines the
serotonin reuptake inhibitor potency of a range of narcotic
analgesics. It indicates that Phenanthrene opioids (with an
oxygen bridge between C4 and C5), such as morphine (group I,
see original paper), did not act as serotonin reuptake inhibitors at
all. Phenanthrene and nonphenanthrene opioids such as
levorphanol and levomethorphan (group II), and d-
propoxyphene and methadone (group III) did act as serotonin
reuptake inhibitors. I have made enquiries of many researchers,
including Toll and Codd but no-one seems to know of any other
data on the serotonin reuptake inhibitor potency of narcotic
analgesics (12,18), except recent additions above i.e.(16,17). See
also PDSP for possible recent additions of
data http://pdsp.med.unc.edu/

References to cases involving tramadol: (19-29)

References to cases involving pethidine: (3, 6, 30-50)

:
 References to cases involving dextromethorphan and
propoxyphene: (5, 8, 51, 52)

References to cases involving fentanyl: (53-60)

In my opinion the Noble case report of a fatality was probably

serotonin toxicity; so as predicted from Codds data there is a
question mark over fentanyl: however its potency as an
serotonin reuptake inhibitor is low, so as expected (and like
pethidine) it has been reported to have been used with impunity.
The more recent Roy case is another peculiar example of
reactions with venlafaxine; this is a drug that seems to produce
unexpected interactions with a variety of other classes of drugs
not adequately explained by its serotonin reuptake inhibitor
action.

Uncertain: (61).

In summary: Morphine, codeine, oxycodone, buprenorphine do

not precipitate serotonin toxicity with monoamine oxidase
inhibitors. Pethidine (meperidine), tramadol, methadone and
fentanyl, propoxyphene, dextromethorphan, are borderline. They
are weakly serotonergic and some may precipitate serotonin
toxicity which must be assumed to be dose dependant.

My conclusion in the BJA paper was: In summary, morphine,

codeine, oxycodone and buprenorphine are now known not to be
SRIs and they do not precipitate serotonin toxicity with MAOIs.
Pethidine, tramadol, dextromethorphan and methadone
definitely are weak SRIs (see Table 2), and may infrequently
precipitate dose-dependant serotonin toxicity (when
administered in conjunction with any type of MAOI), but
perhaps only in large doses or susceptible individuals. Our
ability to estimate the risk with particular drugs with any
precision is compromised by a lack of systematically recorded
:
 data on the clinical toxicity of these drugs, and also by the lack
of pharmacological data concerning their precise potency, as
SRIs or releasers, using the latest assay techniques. For some
drugs (propoxyphene, pentazocine, fentanyl, remifentanil and
congeners) there is no SRI affinity data at all, and we have to
rely on interpolations and the presence or absence of clinical
reports (Table 2). It is to be hoped that increasing understanding
and awareness of this situation will stimulate further research
that will answer these remaining questions.

However, the clinical situation and the risks are now more
clearly defined and understood and the information herein will
enable many clinicians to be more confident when making
decisions about patient management. Choices involving the
known serotonergic opioids can now be made in particular
clinical situations by balancing the advantages and
disadvantages that there may be for individual patients with
respect to particular drugs. The level of risk with known
serotonergic opioids is probably low, but its unpredictable and
serious nature makes it difficult to form judgments. All other
factors being equal, it would seem prudent to use the drugs
known not to be SRIs where possible. These judgments may be
tempered by the knowledge that any reaction is dose-dependent
and that we are now confident that reactions can be successfully
treated, if severe, with 5-HT2A antagonists.
References
1. Gillman, PK, Monoamine oxidase inhibitors, opioid
analgesics and serotonin toxicity. British Journal of
Anaesthesia, 2005. 95: p. 434-441.

2. Churchill-Davidson, HC, Anesthesia and Monoamine-

Oxidase Inhibitors. Br Med J, 1965. 5433: p. 520.

3. Evans-Prosser, A, The use of pethidine and morphine in the

:
 presence of monoamine oxidase inhibitors. British Journal of
Anaesthesia, 1968. 40: p. 279.

4. Peeters-Asdourian, C, [Fatal drug interactions]. Rev Med

Brux, 1986. 7(9): p. 570.

5. Shamsie, SJ and Barriga, C, The hazards of monoamine

oxidase inhibitors in disturbed adolescents. Canadian Medical
Association Journal, 1971. 104: p. 715.

6. Pollock, RA and Watson, RL, Malignant hyperthermia

associated with hypocalcaemia. Anesthesiology, 1971. 34: p.
188.

7. Gong, SN and Rogers, KJ, Role of brain monoamines in the

fatal hyperthermia induced by pethidine or imipramine in rabbits
pretreated with pargyline. Br J Pharmacol, 1971. 42(4): p. 646P.

8. Rivers, N and Horner, B, Possible lethal interaction between

Nardil and dextromethorphan. Canadian Medical Association
Journal, 1970. 103: p. 85.

9. Gillman, PK, Serotonin syndrome: history and risk.

Fundamental and Clinical Pharmacology, 1998. 12(5): p. 482-
491.

10. Gillman, PK, Serotonin toxicity, serotonin syndrome: 2006

update, overview and
analysis. www.psychotropical.com/SerotoninToxicity, 2006: p.
Epub 1-125.

11. Giusti, P, et al., Effect of acute and chronic tramadol on

[3H]-5-HT uptake in rat cortical synaptosomes. British Journal
of Pharmacology, 1997. 122(2): p. 302-6.

12. Codd, EE, et al., Serotonin and norepinephrine uptake

:
 inhibiting activity of centrally acting analgesics: structural
determinants and role in antinociception. Journal of
Pharmacology and Experimental Therapeutics, 1995. 274(3): p.
1263-70.

13. Bamigbade, TA, et al., Actions of tramadol, its enantiomers

and principal metabolite, O-desmethyltramadol, on serotonin (5-
HT) efflux and uptake in the rat dorsal raphe nucleus. British
Journal of Anaesthesia, 1997. 79(3): p. 352-6.

14. Frink, MC, et al., Influence of tramadol on neurotransmitter

systems of the rat brain. Arzneimittelforschung, 1996. 46(11): p.
1029-36.

15. Lomenzo, SA, et al., Synthesis and Biological Evaluation of

Meperidine Analogues at Monoamine Transporters. J Med
Chem, 2005. 48(5): p. 1336-1343.

16. Barann, M, et al., Effects of tramadol and O-demethyl-

tramadol on human 5-HT reuptake carriers and human 5-HT3A
receptors: a possible mechanism for tramadol-induced early
emesis. Eur J Pharmacol, 2006. 531(1-3): p. 54-8.

17. Rothman, RB and Baumann, MH, Therapeutic Potential of

Monoamine Transporter Substrates. Current Topics in Medicinal
Chemistry, 2006. 6: p. 1845-1859.

18. Toll, L, et al., Standard binding and functional assays related

to medications development division testing for potential
cocaine and opiate narcotic treatment medications. NIDA
Research Monograph, 1998. 178: p. 440-66.

19. Lange-Asschenfeldt, C, et al., Serotonin syndrome as a result

of fluoxetine in a patient with tramadol abuse: plasma level-
correlated symptomatology. Journal of Clinical
Psychopharmacology, 2002. 22(4): p. 440-1.
:
 20. Reus, VI and Rawitscher, L, Possible interaction of tramadol
and antidepressants. American Journal of Psychiatry, 2000.
157(5): p. 839.

21. Kesavan, S and Sobala, GM, Serotonin syndrome with

fluoxetine plus tramadol. Journal of the Royal Society of
Medicine, 1999. 92(9): p. 474-5.

22. de Larquier, A, et al., [Serotoninergic syndrome after

combining tramadol and iproniazid]. Therapie, 1999. 54(6): p.
767-8.

23. Calvisi, V and Ansseau, M, Clinical case of the month.

Mental confusion due to the administration of tramadol in a
patient treated with MAOI. Rev Med Liege, 1999. 54(12): p.
912-3.

24. Lantz, MS, Buchalter, EN, and Giambanco, V, Serotonin

syndrome following the administration of tramadol with
paroxetine. International Journal of Geriatric Psychiatry, 1998.
13(5): p. 343-345.

25. Mason, BJ and Blackburn, KH, Possible serotonin syndrome

associated with tramadol and sertraline coadministration. Annals
of Pharmacotherapy, 1997. 31: p. 175-177.

26. Egberts, ACG, ter Borgh, J, and Brodie-Meijer, CCE,

Serotonin syndrome attributed to tramadol addition to
paroxetine therapy. International Clinical
Psychopharmacology, 1997. 12(3): p. 181-182.

27. Hernandez, AF, et al., Fatal moclobemide overdose or death

caused by serotonin syndrome? Journal of Forensic
Sciences, 1995. 40: p. 128-130.

28. Raffa, RB, Reimann, W, and Shank, RP, Opiod and

:
 nonopiod components independently contribute to the
mechanism of action of tramadol, an atypical opiod analgesic.
Journal of Pharmacology and Experimental Therapeutics, 1992.
260: p. 275-285.

29. Driessen, B and Reimann, W, Interaction of the central

analgesic tramadol, with the uptake and release of 5-
hydroxytryptamine in the rat brain in vitro. British Journal of
Pharmacology, 1992. 105: p. 147-151.

30. Mitchell, RS, Fatal toxic encephalitis occurring during

iproniazid therapy in pulmonary tuberculosis. Annals of Internal
Medicine, 1955. 42: p. 417-424.

31. Papp, C and Benaim, S, Toxic effects of iproniazid in a

patient with angina. British Medical Journal, 1958. 2: p. 1070-
1072.

32. Palmer, H, Potentiation of pethidine. British Medical

Journal, 1960. 2: p. 944.

33. Shee, JC, Dangerous potentiation of pethidine by iproniazid

and its treatment. British Medical Journal, 1960. 2: p. 507-509.

34. Brownlee, G and Williams, GW, Potentiation of

amphetamine and pethidine by monoamine oxidase inhibitors.
Lancet, 1961. 1([letter]): p. 669.

35. Clement, AJ and Benazon, D, Reactions to other drugs in

patients taking monoamine oxidase inhibitors. Lancet, 1962.
2([letter]): p. 197-198.

36. Cocks, DP and Passmore-Rowe, AH, Dangers of

monoamine oxidase inhibitors. British Medical Journal, 1962.
2([letter]): p. 1545-1546.
:
 37. Denton, PH, Borrelli, VM, and Edwards, NV, Dangers of
monoamine oxidase inhibitors. British Medical Journal, 1962. 2:
p. 1752-1753.

38. London, DR and Milne, MD, Dangers of monoamine

oxidase inhibitors. British Medical Journal, 1962. 2: p. 1752.

39. Pells Cocks, D and Passmore-Rowe, A, Dangers of

monoamine oxidase inhibitors. British Medical Journal, 1962. 2:
p. 1545-6.

40. Reid, NCRW and Jones, D, Pethidine and phenelzine. British

Medical Journal, 1962. 1: p. 408.

41. Taylor, DC, Alarming reaction to pethidine in patients on

phenelzine. Lancet, 1962. 2: p. 401-402.

42. Nymark, M and Møller Nielsen, I, Reactions due to the

combination of monoamineoxidase inhibitors with thymoleptics,
Pethidine or methylamphetamine. Lancet, 1963. 2([letter]): p.
524-525.

43. Vigran, IM, Dangerous potentiation of meperidine

hydrochloride by pargyline hydrochloride. Journal of the
American Medical Association, 1964. 187([letter]): p. 953-954.

44. Jounela, AJ, Mattila, MJ, and Knoll, J, Interaction of

selective inhibitors of monoamine oxidase with pethidine in the
rabbit. Biochemical Pharmacology, 1977. 26: p. 806-808.

45. Leander, JD, Batten, J, and Hargis, GW, Pethidine

interaction with clorgyline, pargyline, or 5- hydroxytryptophan:
lack of enhanced pethidine lethality or hyperpyrexia in mice. J
Pharm Pharmacol, 1978. 30(6): p. 396-8.

46. Rawlins, MD, Drug interactions and anaesthesia. Br J

:
 Anaesth, 1978. 50(7): p. 689-93.

47. Meyer, D and Halfin, V, Toxicity secondary to meperidine in

patients on monoamine oxidase inhibitors: a case report and
critical review. Journal of Clinical Psychopharmacology, 1981.
1: p. 319-321.

48. Starr, C, Interaction between pethidine and selegiline.

Lancet, 1991. 337(8740): p. 554.

49. Zornberg, GL, Bodkin, JA, and Cohen, BM, Severe adverse
interaction between pethidine and selegiline. Lancet, 1991. 337:
p. 246.

50. Gillman, PK, Possible serotonin syndrome with

moclobemide and pethidine. Medical Journal of Australia, 1995.
162([letter]): p. 554.

51. Garbutt, JC, Potentiation of propoxyphene by phenelzine.

American Journal of Psychiatry, 1987. 144(2): p. 251-2.

52. Zornberg, GL, Adverse interaction between propoxyphene

and phenelzine. American Journal of Psychiatry, 1993. 150(8):
p. 1269-1270.

53. Noble, WH and Baker, A, MAO inhibitors and coronary

artery surgery: a patient death. Canadian Journal of
Anaesthesia, 1992. 39(10): p. 1061-1066.

54. Insler, SR, et al., Cardiac surgery in a patient taking

monoamine oxidase inhibitors: an adverse fentanyl reaction.
Anesth Analg, 1994. 78(3): p. 593-7.

55. Wells, DG and Bjorksten, AR, Monoamine oxidase

inhibitors revisited. Can J Anaesth, 1989. 36(1): p. 64-74.

56. Fobe, F, et al., Heart-transplant and mono-amine oxidase

:
 inhibitors. Acta Anaesthesiol Belg, 1989. 40(2): p. 131-8.

57. Stack, CG, Rogers, P, and Linter, SPK, Monoamine oxidase

inhibitors and anaesthesia. British Journal of Anaesthesia, 1988.
60: p. 222-227.

58. el-Ganzouri, AR, et al., Monoamine oxidase inhibitors:

should they be discontinued preoperatively? Anesth
Analg, 1985. 64(6): p. 592-6.

59. Michaels, I, et al., Anesthesia for cardiac surgery in patients

receiving monoamine oxidase inhibitors. Anesth Analg, 1984.
63(11): p. 1041-4.

60. Roy, S and Fortier, LP, Fentanyl-induced rigidity during

emergence from general anesthesia potentiated by venlafexine.
Can J Anaesth, 2003. 50(1): p. 32-5.

61. Brown, DD and Waldron, DH, An unusual reaction to

tranylcypromine. Practitioner, 1962. 189: p. 83-86.

" #
PsychoTropical Research | Dr Ken Gillman
: