Swapping from one MAOI to another MAOI

by | Last updated Nov 22, 2020 | Published on Sep 13, 2019 | Anti-Depressants, MAOIs

The requirement or desire to swap from one MAOI to another MAOI is something that will be an uncommon occurrence. Furthermore, it will be an urgent need even more rarely. It may be indicated, for instance, because of the excessive weight gain, sexual dysfunction, or oedema, that occur with phenelzine. Because opinion exists in the literature suggesting dovetailing, or a direct swap, is a potentially risky thing to do, some discussion about this is educative.

Insofar as I have been able to trace the original texts which postulate these sorts of dangers, I have one particular comment to make: case reports are notoriously unreliable. Also, they may be written by clinicians with little experience and who have an incomplete understanding of pharmacology, or toxicology, and they often contain errors of fact (they are poorly refereed). If such texts are books, they may not be peer-reviewed at all.


First, there is no known, or even hypothesized, mechanism of interaction that would predict or cause a problem.

Second, neither is there a basis for postulating a pharmaco-kinetic interaction.

Third, nor is there a basis for a major pharmaco-dynamic interaction.

That leaves a mystery, or possibly a phantom? This is because, without any scientific basis for proposing an interaction, case reports are really more like ghost-hunting.

My extensive experience of analysing hundreds of case reports of ST indicates clearly that the overwhelming majority of case reports are misleading*, and they often involve supposed interactions that have no known basis, in fact or theory [1]. To make decisions based on such reports has repeatedly proved to be inappropriate and the resultant actions have in some cases had serious negative consequences.

*This is why many reputable journals decline to publish case reports [1].

The literature is replete with inappropriate and groundless injunctions against a host of perfectly safe drug combinations (see my other papers for a detailed analysis of this topic in relation to ST) and various ‘official’ bodies like the WHO and the FDA have been repeatedly guilty of issuing such scientifically groundless injunctions: recent examples are warnings about ‘serotonergic’ drugs precipitating ST if combined with the anti-emetic 5-HT3 antagonists, and about ST with Triptans. Such ‘cry-wolf’ warnings are time-wasting and confuse and misdirect practicing clinicians. So, adopting the careful conservative approach is not the ‘win-win’ scenario that such cautious analysts suppose it to be.

In routine clinical practice the maxim ‘start low and go slow’ is wisely adhered to (and only change one drug or dose at a time). When a changeover is being considered, or is indicated, in a patient who is severely ill, and in danger because of that, a degree of risk, imagined or real, is acceptable. In less urgent circumstances the patient and clinician may be well-advised to opt for a cautious approach.

The history, as of 2020, of accumulated references

In 60 years of MAOI use there are only a handful of uncertain and disparate reports of supposed difficulties: these are of a variety of different clinical presentations that are not indicative of a cause-effect relationship involving an MAOI-MAOI interaction.

Supposed adverse events

The following are the relevant contributions that I am aware of, in the published literature, relating to direct MAOI to MAOI change-overs: [2-13]. Concerning Torre et al. see ‘case 2’. As with so many case-reports, most of these contain insufficient information to draw reliable conclusions.

None of them are much help, nor do they provide a rational or substantive basis for prohibition of a direct swap-over of one MAOI to another MAOI.

It is notable that of these incomplete and unconvincing reports, one suggests subarachnoid haemorrhage, one a stroke, and another serotonin toxicity.

One might also observe that these reports include all possible combinations of switch drug and switch sequence; hydrazine to hydrazine, hydrazine to TCP (non-hydrazine) and vice versa.

It is highly improbable that all of these represent a cause-effect interaction, because the required mechanism would be different for each of them.

The most parsimonious explanation is that none of them represent a cause-effect relationship between the changing drug regime and the outcome reported.

An additional comment I would make from my extensive experience of analyzing case reports of serotonin toxicity (ST) is that surprising and anomalous case reports often have an alternative explanation that has not been considered. ST has a categoric and predictable nature which provides examples of this; e.g. when people are supposed to have developed severe ST following a particular ingestion of drugs (which pharmacology predicts cannot cause serious ST). In several instances I have gone back to those who have reported these cases and suggested to them that further inquiry will reveal that a drug of type X must also have been ingested. Toxicology, or more penetrating questioning of the patient, has revealed exactly that to be the case. Indeed, such a chain of reasoning was what led to the discovery of the MAOI property of methylene blue.

Lack of adverse events

One paper reported a small series of 8 cases where it was accomplished without a problem [14], and another a couple of safe transitions [6]. I have personally done it without any problem, but only on a couple of occasions, as have associates, and various people who have been in contact via my web site. Indeed, I now estimate that about a dozen patients who have done so of their own accord have reported safe results to me via the website: one man has reported changing from TCP>PLZ>TCP several times with quite high doses without any problems.

A possible mechanism for hypertension

It is well recognised that abrupt cessation of antihypertensive treatment can cause rebound hypertension; indeed, this is a not uncommon presentation in emergency departments. It is forgotten that MAOIs are anti-hypertensive drugs, and, as I have reviewed elsewhere, were indeed used for the treatment of hypertension in the 1960s and 1970s. I have seen patients who have developed high blood pressure when well-meaning primary-care physicians have stopped the ‘dangerous-old-antidepressants-we-don’t-use-anymore’ that the (doddery old) specialist has been giving because he does not know about the wonderful new drugs we now have (that the young lady drug rep in the short skirt who took me to lunch told me all about). I encountered some primary care physicians who exhibited extraordinary hubris and careless arrogance, usually for the purpose of ‘big-noting’ themselves to their private patients.

Here is an incidental tip for patients: beware of primary care physicians who repeatedly recommend the latest drug to come on the market, especially when they are changing the treatment previously instituted by a specialist. They may also have a clock, leather folder, blotting pad, box of pens etc. with the trade name of the drug in question emblazoned on it!

I have seen patients on long-term MAOI treatment who have developed idiopathic hypertension during the course of that treatment, which was ‘disguised’ by the MAOI. These patients then had substantial rises in blood pressure on cessation of the MAOI. Indeed, one of them actually had a small CVA whilst waiting for an appointment to see me, to decide on future treatment. The primary care doctor had already (unilaterally) instructed her to cease the tablets prior to the appointment with me. If that patient had already restarted the other MAOI, where then would the blame for her CVA have been laid? The case reported by Gelenberg fits this possibity {Gelenberg, 1984 #19716}.

Such observations add yet more weight my recommendation that one should monitor sitting and standing BP regularly in everyone taking MAOIs, especially when changing treatment.

Opinion and conclusion

If there is ever good reason to swap rapidly, it is reasonable to do it, because there is:

No theoretical basis to suggest it might be contra-indicated

It has clearly been done many times without any problem

Existing reports do not constitute substantive evidence to the contrary.

Also, monitor sitting and standing BP especially carefully and frequently when changing treatment (three times daily? and more frequently for hospital patients?).

There are some simple principles of pharmacology relating to mixing medications which suggest that it is best to make changes slowly, and to only make one change at a time. Because the period for ongoing pharmacological effects from MAOIs is long, like weeks rather than days, I would suggest that the following regime has a theoretical basis which recommends it. Add a small dose of the new drug (TCP 5 mg, PLZ 7.5 mg), without changing the previous regime, and then build up the dose to the minimum therapeutic level slowly, i.e. over a couple of weeks, and then begin to taper off the previous treatment. If that can be achieved with adequate monitoring and supervision that would be my preferred approach.


1. Gillman, P.K., Extracting value from case reports: lessons from serotonin toxicity. Anaesthesia, 2006. 61: p. 419-422.

2. Bazire, S.R., Sudden death associated with switching monoamine oxidase inhibitors. Drug Intell Clin Pharm, 1986. 20(12): p. 954-6.

3. Gelenberg, A., Switching MAOIs—-the sequel. Biological Therapies in Psychiatry, 1985. 8: p. 41.

4. Jefferson, J.W., Problems with switching rapidly from one MAOI to another. J Clin Psychiatry, 1998. 59(2): p. 87.

5. Mattes, J.A., Stroke resulting from a rapid switch from phenelzine to tranylcypromine. J Clin Psychiatry, 1998. 59(7): p. 382.

6. Polnak, J.F., et al., Monoamine Oxidase Inhibitor Switching Strategies: No Adverse Events Associated With Outpatient Cross-taper or Inpatient Rapid Switch. J Clin Psychopharmacol, 2018. 38(1): p. 92-94.

7. Safferman, A.Z. and S.J. Masiar, Central nervous system toxicity after abrupt Monoamine inhibitor switch: a case report. Pharmacotherapy, 1992. 26: p. 337-338.

8. Schrire, I., Collapse after Parstelin. Brit Med J, 1963. Collapse after Parstelin(ii): p. 748.

9. Torre, L.E., R. Menon, and B.M. Power, Prolonged serotonin toxicity with proserotonergic drugs in the intensive care unit. Crit Care Resusc, 2009. 11(4): p. 272-5.

10. True, B.L., B. Alexander, and B. Carter, Switching monoamine oxidase inhibitors. Drug Intell Clin Pharm, 1985. 19(11): p. 825-7.

11. True, B.L., B. Alexander, and B.L. Carter, Comment: Switching MAO inhibitors. Drug Intell Clin Pharm, 1986. 20(5): p. 384-5.

12. Chandler, J.D., Switching MAOIs. J Clin Psychopharmacol, 1987. 7: p. 438 https://journals.lww.com/psychopharmacology/Citation/1987/12000/Switching_MAOIs.24.aspx.

13. Gelenberg, A., Switching MAOIs. Biological Therapies in Psychiatry, 1984. 7(9): p. 33-36.

14. Szuba, M.P., M. Hornig-Rohan, and J.D. Amsterdam, Rapid conversion from one monoamine oxidase inhibitor to another [see comments]. Journal of Clinical Psychiatry, 1997. 58(7): p. 307-10.

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