MAOIs (Parnate, Nardil): Misconceptions and Questions No. 1

This section will be added to as and when additional relevant questions and issues arise.

Any readers who are not familiar with my website may like to look for themselves at my scientific publications and credibility in this field. There are few practising psychiatrists who have the publications, experience and knowledge that is summarised in this website.

It is, unfortunately, necessary to state clearly from the beginning that much of what is published by doctors in books and journals about MAOIs is either poorly informed, or just plain wrong. As an example, much of the information that comes with MAOIs (the PI, or product information sheet) contains inaccurate material concerning, among other things: serotonin toxicity, drug interactions generally, and dietary tyramine.

As always with the Internet there is a little information that is good, but sadly it is usually drowned by the mass of misinformation. My scientific publications concerning MAOIs and other material on my website should be consulted for detailed information. This series of notes will simply deal with errors and misconceptions briefly, without always going into detailed explanations of why they are incorrect, especially since these can be usually be found elsewhere in my writings.

I will deal with points and misconceptions that seem common amongst my colleagues and with patients, and from what I see on the Internet: e.g.

http://www.askapatient.com/viewrating.asp?drug=12342&name=PARNATE

One Q was (not at askapatient):

“Is it true that treatment with parnate is contraindicated for patients with hypertension? ... I have treatment resistant depression but also suffer from hypertension …”

Their Answer: Hello, I am a psychiatrist. Yes, that is a very real concern. Using Parnate could result in a life-threatening elevation of your blood pressure, if it is already high. … (followed by more incorrect info).

My comment: this answer, by someone who states they are a psychiatrist, exemplifies one of the commonest errors and misconceptions that even specialists seem to have about MAOI drugs. The psychiatrist’s answer is quite wrong: MAOIs actually lower blood pressure, and were indeed used for treatment of hypertension back in the 1960s before better drugs became available (1-3). Many hypertensive patients who take MAOIs for depression are able to reduce their other anti-hypertensive medication, and sometimes even stop it completely, whilst they are on MAOIs. They will of course have to restart anti-hypertensive medication if and when they cease MAOIs.

It is also important to recognise that hypertension can (re-)emerge after cessation of MAOIs even in people who did not have apparent essential hypertension prior to taking MAOIs. One presumes the explanation for this is that whilst on treatment with MAOIs the person has developed underlying essential hypertension which has been effectively treated by the MAOI and therefore is only revealed when the drug is ceased. I have certainly seen this happen several times.

From askapatient.com

Comment: …[BP] freaked me out so I bought a BP monitor and sure enough every morning my BP was around 115/75 which is normal but after taking my first dose of Parnate (2x10mg) it would shoot up to at least 160/90. This wasn't diet related as I checked it for 4 days and made sure I wasn't taking anything even remotely risky for MAOI takers.

My Answer: It is important to get this issue about blood pressure into perspective. Healthy vigorous exercise will increase systolic blood pressure to 200 mmHg (or more) within about five minutes, where it will remain throughout the duration of the exercise: think about the craze for marathon running! All such participants must be supposed to be at higher risk of stroke etc. than the few people who get a little occasional hypertension with MAOIs. This recent Finnish study (4) involved >1,000 normal participants on whom blood pressure data was gathered during exercise and the average BP was 200 mmHg, obviously many people were higher than that. Weight lifting, for instance, raises the blood pressure levels as high as 450 mmHg (5). Has weightlifting been banned? I will not even mention BP driving (6) or sexual intercourse (7).

There are millions of Americans walking round with blood pressures in excess of 160 much of the time, often unrecognised & untreated.

With MAOIs some people do get a short-lived rise in BP for approx. 30-90 minutes post-dose (my estimate is 2-5% of people on doses of up to 50 mg per day), perhaps more so with larger doses. There is no suggestion or evidence that this is severe or dangerous. In my experience that response tends to lessen as you get used to the drug. If it causes subjective symptoms which require action then spreading the dose out will help. In order to understand the how and why of dosing it is useful to understand that the half life of Parnate is very short. It varies in different people but it is generally less than 2 hours (8-10). This is relevant for its possible (non-therapeutic) effects not related to MAO inhibition (e.g. via TAA receptors, see other notes). However because it is an irreversible inhibitor its half life is not relevant to what we think is the main therapeutic effect, which is MAO inhibition.

So, what this almost certainly means is that for MAOI therapeutic effect it does not matter at all whether you take one single dose or split it up. Indeed it is probably possible to take it on alternate days. Is all that matters is whether the total dose taken is sufficient to inhibit any new enzyme which has been synthesised by the body since the last dose. However, to the extent that other effects may be mediated in other ways, those are likely to be dependent on the concentration of the drug in the blood and tissues, then the half life is relevant. Therefore, if the objective is to minimise side effects by spreading the effect as evenly as possible in the first part of the day it is logical to take a dose every couple of hours.

For many people Parnate has less side effects than most other drugs, but insomnia is one of the commoner undesirable effects. It seems clear that, in the majority of people, the earlier in the day that the dose is taken the less insomnia is experienced. If it is possible to take the whole daily dose first thing in the morning (on waking) that is the ultimate way of minimising insomnia. If that does not work then splitting the dose up into smaller bits taken at intervals of about two hours or so is the next best solution. It is usually best not to take any of the doses after the middle of the day. However, there are no absolute rules and experimenting to find out what is best for each individual usually gives a satisfactory resolution for any problems.

References

1.    Datey, KK, Namda, NC, and Dalvi, CP, Management of hypertension with pargyline hydrochloride (Eutonyl). J. Postgrad. Med., 1965. 11(3): p. 126-32.
2.    Kavanaugh, GJ, Sheps, SG, Fairbairn, JF, 2nd, Osmundson, PJ, et al., Experience with Pargyline Hydrochloride (Nonhydrazine Monoamine Oxidase Inhibitor) as an Antihypertensive Agent: Preliminary Observations in 32 Patients. Minn. Med., 1965. 48: p. 731-5.
3.    Oates, JA, Seligmann, AW, Clark, MA, Rousseau, P, et al., The relative efficacy of guanethidine, methyldopa and pargyline as antihypertensive agents. N. Engl. J. Med., 1965. 273(14): p. 729-34.
4.    Kurl, S, Laukkanen, JA, Rauramaa, R, Lakka, TA, et al., Systolic blood pressure response to exercise stress test and risk of stroke. Stroke, 2001. 32(9): p. 2036-41.
5.    Haykowsky, MJ, Findlay, JM, and Ignaszewski, AP, Aneurysmal subarachnoid hemorrhage associated with weight training: three case reports. Clin J Sport Med, 1996. 6(1): p. 52-5.
6.    Simonson, E, Baker, C, Burns, N, Keiper, C, et al., Cardiovascular stress (electrocaridographic changes) produced by driving an automobile. Am. Heart J., 1968. 75(1): p. 125-35.
7.    Xue-Rui, T, Ying, L, Da-Zhong, Y, and Xiao-Jun, C, Changes of blood pressure and heart rate during sexual activity in healthy adults. Blood Press. Monit., 2008. 13(4): p. 211-7.
8.    Baker, GB, Urichuk, LJ, McKenna, KF, and Kennedy, SH, Metabolism of monoamine oxidase inhibitors. Cell Mol Neurobiol, 1999. 19(3): p. 411-26.
9.    Lang, A, Geissler, HE, and Mutschler, E, [Determination and comparison of the plasma and urine concentrations in men given tranylcypromine stereoisomers]. Arzneimittelforschung., 1979. 29(1): p. 154-7.
10.    Baselt, RC and Stewart, CB, Determination of serum and urine concentrations of tranylcypromine by electron-capture gas-liquid chromatography. J Anal Toxicol (September-October 1977) 1(5): 215-217 1977. 1(2): p. 215-217.