This brief commentary summarises the published research concerning MAOIs, platelet MAO inhibition, and blood pressure changes viz. hypotension. These papers do not have adequate data to make them comparable and useful. I have measured the sitting and standing blood pressure of hundreds of patients myself on MAOIs (and TCAs). Because that was done mostly on an outpatient basis I performed sitting vs. standing measurements rather than lying vs. standing measurements. From the early days of computer databases I recorded these measurements and used them to plot graphs on-screen to illustrate to patients the typical patterns of change in blood pressure with increasing MAOI dose.
I was taught that lowering of blood pressure was an inevitable therapeutic effect of MAOIs (which it most certainly is, see below) and that therefore one should increase the dose progressively until definite postural hypotension was observed. That is not to say that improvement, sometimes even maximal response, cannot occur in the absence of hypotension. Rather it suggests that one cannot be confident one is giving a maximally effective dose unless hypotension is occurring. There are exceptions to this and in my experience a small percentage of patients (<5%) do not appear to experience significant hypotension even at doses (of tranylcypromine TCP) between 80 and 120 mg daily. I do not recall using doses above 120 mg daily).
The starting dose, and the rapidity with which the dose is increased, has a crucial effect on the degree of postural hypotension manifested, because adaption to postural hypotension occurs over a period of 7 to 10 days. This is probably due to the change in sensitivity of receptors, rather analogous to beta adrenergic receptor down-regulation with antidepressant treatment.
The bar graph in this link illustrates the typical pattern of blood pressure change with MAOIs. Because the degree of postural hypotension varies with the length of time for which a constant dose has been taken it is self-evident that any reports which do not give full information regarding baseline blood pressure and exact time relationship between the blood pressure measurements and initiation of changes in dose will be of limited value and be difficult to interpret.
* direct Link to bar graph and spreadsheet (these links are in the MAOI section sub-menu under ‘antidepressants’ main menu, the pdf selection menu is located at the bottom L of the page, so scroll down to see it):
Furthermore, when blood pressure changes are small in the early phase of treatment, the blood pressure only drops a little bit for a short time after standing, then recovers to a higher level (as illustrated in the bar graph).
This leads us to the second problem with all of the reports below which is that serial measurements on standing have not been performed. For research purposes in cases of idiopathic orthostatic hypotension measurements would be done with the body tilting procedure and measurements would be continued for three minutes. In routine office practice I found that was not practical and that measurements done immediately on standing and after standing for one minute were a good practical compromise. Papers that do not properly describe the method of blood pressure measurement are subject to uncertainties of interpretation.
Whilst this may sound complicated, once the system is established it is straightforward and there is a spreadsheet that can be downloaded on which to enter values. The spreadsheet will produce a graph similar to the one illustrated in my PDF. It is difficult to interpret tabulated blood pressure measurements but much easier to see the pattern and understand what is going on with a graph.
Lowering of Blood Pressure: a Therapeutic Effect of MAOIs
On reading this you may understand why it is frustrating to read much of what is written about MAOIs. Many doctors still believe that MAOIs raise blood pressure. Back in the 1960s they were more widely used as anti-hypertensive drugs than they were as antidepressants: the following references attest to that (1-10).
Many patients on MAOIs will be able to lower, or cease, previously necessary anti-hypertensive drugs.
It is therefore imprecise to describe hypotension as a ‘side-effect’, it is one of their therapeutic actions. Even now we do not understand the exact mechanism of this action, but it is reasonable to continue to suppose that inhibition of an MAO, lowering of blood pressure and mood elevation are closely linked via the same pharmacologically induced changes in the brain. This brings us to the next bit of evidence which is the relationship between MAO inhibition and blood pressure.
MAO Inhibition in Platelets and Lowering of Blood Pressure
Measurement of platelet MAO inhibition is now only of academic interest for two reasons: first, no laboratories are capable of routinely measuring it in blood samples; second, there is not a substantive and reliable body of data relating MAO inhibition to blood pressure changes.
Furthermore, only MAO-B is present in platelets and the relationship between inhibition of MAO-B in platelets and inhibition of MAO-A & B in the brain is not established. For these and other reasons it plays no part in clinical management and has not been the subject of any research for some considerable time.
MAOs and Blood Pressure: Clinical Data
In a 1983 paper Kronig et al (11) stated "it is striking that there are no studies of MAOIs that actually report BP data".
The most recent paper reporting data that I am aware of(12) illustrates that the problems described above continue. They state “both drugs [TCP & PLZ] induced orthostatic hypotension in a similar manner, in correspondence to previous reports (11, 13, 14)at similar dose levels, and that both drugs had no effect on HR or supine BP”. Their data concerns only 16 subjects.
Even now I find myself shaking my head in disbelief when I read such material. These are drugs which were used as anti-hypertensives over 50 years ago! and even now psychiatrists are congratulating themselves for discovering hypotension as a ‘side effect’!
About all one can conclude from such crude data is that a substantial percentage of patients on the typical doses that most people have used have developed measurable and probably significant postural hypotension. That is news! It is very difficult to look at such observations without commenting that psychiatric fraternity have been persistently dilatory and unscientific in their clinical observations.
Other papers reporting data that I am aware of include:(13-20).
Compared to the large number of patients (hundreds) on which my data and statements are based the quality and quantity of the published literature (tens) is of little extra use.
1. Gessa, GL, Cuenca, E, and Costa, E, On the mechanism of hypotensive effects of MAO inhibitors. Ann. N. Y. Acad. Sci., 1963. 107: p. 935-44.
2. Onesti, G, Novack, P, Ramirez, O, Brest, AN, et al., Hemodynamic Effects of Pargyline in Hypertensive Patients. Circulation, 1964. 30: p. 830-5.
3. Brest, AN, Hemodynamic Response to Antihypertensive Drug Therapy. JAMA, 1965. 192: p. 41-4.
4. Datey, KK, Namda, NC, and Dalvi, CP, Management of hypertension with pargyline hydrochloride (Eutonyl). J. Postgrad. Med., 1965. 11(3): p. 126-32.
5. 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.
6. 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.
7. Rangle, RV, The Antihypertensive and Hypoglycemic Effects of Pargyline Hydrochloride. Angiology, 1965. 16: p. 351-4.
8. Van Dyne, JR, Pargyline Hydrochloride in Treatment of Resistant Hypertension. N. Y. State J. Med., 1965. 65: p. 1672-5.
9. Campione, KM, Effect of antihypertensive (pargyline hydrochloride-methyclothiazide) therapy in three types of hypertension: preliminary report after one year of observation. J. Am. Geriatr. Soc., 1966. 14(5): p. 490-6.
10. Lewis, RG and Young, AY, A long-term study with pargyline in the treatment of hypertension. Med. J. Aust., 1967. 1(7): p. 339-41.
11. Kronig, MH, Roose, SP, Walsh, BT, Woodring, S, et al., Blood pressure effects of phenelzine. J Clin Psychopharmacol, 1983. 3(5): p. 307-10.
12. Tulen, JH, Volkers, AC, van den Broek, WW, and Bruijn, JA, Sustained effects of phenelzine and tranylcypromine on orthostatic challenge in antidepressant-refractory depression. J Clin Psychopharmacol, 2006. 26(5): p. 542-4.
13. Georgotas, A, McCue, RE, Friedman, E, and Cooper, TB, A placebo-controlled comparison of the effect of nortriptyline and phenelzine on orthostatic hypotension in elderly depressed patients. J Clin Psychopharmacol, 1987. 7(6): p. 413-6.
14. O'Brien, S, McKeon, P, O'Regan, M, O'Flaherty, A, et al., Blood pressure effects of tranylcypromine when prescribed singly and in combination with amitriptyline. J Clin Psychopharmacol, 1992. 12(2): p. 104-9.
15. Robinson, DS, Nies, A, Ravaris, CL, Ives, JO, et al., Clinical pharmacology of phenelzine. Arch. Gen. Psychiatry, 1978. 35(5): p. 629-35.
16. Andreu, N, Damase-Michel, C, Senard, JM, Rascol, O, et al., A dose-ranging study of selegiline in patients with Parkinson's disease: effect of platelet monoamine oxidase activity. Mov. Disord., 1997. 12(3): p. 293-6.
17. Rabkin, J, Quitkin, F, Harrison, W, Tricamo, E, et al., Adverse reactions to monoamine oxidase inhibitors. Part I. A comparative study. J Clin Psychopharmacol, 1984. 4(5): p. 270-8.
18. Rabkin, JG, Quitkin, FM, McGrath, P, Harrison, W, et al., Adverse Reactions to Monoamine Oxidase Inhibitors. Part II Treatment Correlates and Clinical Management. J Clin Psychopharmacol, 1985. 5: p. 2-9.
19. Lin, SC, Hsu, T, Fredrickson, PA, and Richelson, E, Yohimbine- and tranylcypromine-induced postural hypotension. Am J Psychiatry, 1987. 144(1): p. 119.
20. Cockhill, LA and Remick, RA, Blood pressure effects of monoamine oxidase inhibitors--the highs and lows. Canadian Journal of Psychiatry, 1987. 32(9): p. 803-8.