I am still sometimes asked if nifedipine should be given to patients for them to take as a ‘rescue medication’ if it is thought they may be having a hypertensive episode resulting from consuming tyramine, whilst taking MAOIs.

No, no and no. Do not give nifedipine, to anyone, ever.

This commentary is supplementary to the comments I have already made in the full version of the MAOI monograph which states clearly that ‘immediate-release’ or ‘short-acting’ nifedipne should not be given to patients. Indeed, it would never be used by a hypertension expert, even under close observation in hospital.

Pain and anxiety exacerbate hypertension, so remaining calm and using a benzodiazepine, which will lower BP safely and to a significant and sufficient extent (1-4), is the most useful and safe initial step. It is most unlikely that urgent hospital and specialist assessment will be required, unless a very large ingestion of tyramine is suspected (nowadays that would almost have to be ‘deliberate’), and observation and BP monitoring shows BP increasing beyond 220 mm/Hg or so over a prolonged time (2 hours).

A great majority of BP elevations nowadays are going to be mild, from relatively small amounts of tyramine, and will last only an hour or two and require no intervention.

Evidently, and a little surprisingly, it is still not uncommon practice for doctors, including psychiatrists, to give such medication, usually nifedipine, to patients to self-administer. At least one published article I recall seeing quite recently suggested that strategy, and doubtless many websites do.

Right away, let me advise that for some years it has been possible to state, confidently and emphatically, that using nifedipine (or any other BP ‘rescue’ drug) to rapidly lower BP during a hypertensive urgency is absolutely contra-indicated (hypertensive urgency is BP > 180/120, three measurements, taken whilst calm and at rest!).

The evidence is sufficiently clear that a doctor who advised nifedipine might well lose any resulting damages claim.

I hear a chorus: ‘But surely that risk is worth it to prevent a ‘stroke’ … .’ No, it is not.

The first mistaken assumption to tackle is this: the idea that a tyramine reaction will raise someone’s BP, higher and higher, until their head explodes. That simply is not a plausible scenario. There are two good reasons for that: first, even people with elevated risk, who have known A-V malformations, survive years of episodes of high BP, then might get a sub-arachnoid haemorrhage while just sitting on the toilet.

Second, the degree of elevation of BP caused by ingestion of tyramine is generally no greater than elevations produced by a host of other factors. These include, exercise, sex, stress, driving, anxiety, lifting weights, taking amphetamines (speed, ice) – in fact just living.

Foods have much lower levels of tyramine now, than in past decades. To ingest sufficient tyramine to raise BP high enough, for long enough, to precipitate encephalopathy, heart failure or renal damage would now be nigh on impossible (that is what some of the old cases reports from the 1960s involved, hypertensive encephalopathy and heart failure – not acute sub-arachnoid haemorrhage).

The relatively short duration of BP elevation precipitated by excess tyramine will rarely be more than an hour or two, and the risk of such elevation ‘causing’ sub-arachnoid haemorrhage is minuscule. Again, I hear people say, ‘but I had a case …’. Yes, cases like that do occur, but a myriad of episodes of BP elevation, that are an inevitable part of life, pass without consequence. If you have a defective boat which sinks when it encounters a decent-sized wave, it makes no sense to blame that particular wave. Like waves, BP goes up and down all the time. The ‘fight and flight’ response raises BP as high as tyramine (the mechanism is, after all, the same, viz. sudden release of adrenaline). If evolution had equipped us with such weak blood vessels that they popped regularly when our BP went high, our species would not have survived.


A review twenty years ago (in 1996) stated ‘Not surprisingly, sublingual nifedipine was pulled from the antihypertensive arsenal for hypertensive emergencies after its dismal risk/benefit ratio was publicized, and its widespread use came to a screeching halt (5, 6). It was too good and acted too fast (hence the slow release formulations!).

The product labelling, twenty years ago, for short-acting nifedipine included specific warnings against using the agent for acute blood pressure reduction and for controlling essential hypertension and the FDA declined to approve it for the use of acute hypertension because of its unpredictability and unproven effect and the documented risks. The National Heart Lung and Blood Institute issued a statement saying, in part, that “short-acting nifedipine should be used with great caution (if at all), especially at higher doses, in the treatment of hypertension, angina, and MI.” (7) and it was suggested that the practice should be prohibited (5).

Well, the ‘screeching halt’ bit did not quite happen, despite all the above. Not all doctors are aware of the dangers, it would seem. Another recent review bemoans that ‘old habits die hard’ even when the evidence against them has been substantial and existed for many years. The nifedipine story is certainly an example of that (8), its use has undoubtedly been the cause of many strokes – this is still happening, two decades after the initial warning from the FDA.

When I first prepared the MAOI monograph years ago, I spoke to several physicians with experience in this area and they are all related cases they knew of cerebral injury e.g. cortical blindness, precipitated by nifedipine-induced hypotension.

Thus, for two decades, the overwhelming weight of opinion amongst hypertension experts is that oral nifedipine is not only strongly contraindicated in acute hypertension, but should probably never be used at all.

Powerful BP lowering drugs must only be used under expert supervision in hospital because of the risk of catastrophic consequences from hypoperfusion caused by sudden reduction in blood pressure. This can cause cerebral infarction (9, 10), cortical blindness (11, 12), cardiac insufficiency, angina and renal damage.

If excessive tyramine is ingested the blood pressure starts to increase from about half an hour after ingestion (sooner for liquids on an empty stomach), and remains elevated for 1 – 2 hours: the magnitude and duration of that elevation is dose related, so unless a large amount of tyramine has been ingested (50 – 100 mg) the reaction will be short-lived (about one hour).

An SBP of 180 mmHg or more, sustained over 3 measurements in 10 minutes or so, performed in a calm setting with an accurate sphygmomanometer is now referred to as a ‘hypertensive urgency’. Only if ‘end organ’ dysfunction is present it is called a ‘hypertensive emergency’. End organ dysfunction is uncommon unless DBP is greater than 130 mmHg (13).

In hypertensive urgencies the treatment aim is to reduce BP slowly over 24 – 48 hrs. Since tyramine reactions are self-limiting over 2 – 4 hrs., or rather less with present, typically smaller, tyramine ingestions, it is clear they will very rarely require intervention. The exception to this might be when a large (> 100 mg) ‘deliberate’ tyramine ingestion has occurred and SBP is in excess of 220/130 mm/Hg.

Rapid reduction of hypertension (i.e. within 2 – 4 hours) carries a serious risk of catastrophic adverse effects (13-16) and such treatment is probably inadvisable, even if initiated in a specialist hospital setting.

Several of these recent reviews about hypertensive urgencies make very strong statements about premature treatment and about excessively rapid reductions of blood pressure.

  1. Flanigan: “Often the urgency is more in the mind of the treating physician than in the body of the patient … The compulsive need to treat reaches the pathological in some physicians, especially during the early years in their careers”.
  2. Marik: “Rapid reduction of BP may be associated with significant morbidity … causing ischemia and infarction. it must be lowered in a slow and controlled fashion [over 24 – 48 hrs.] to prevent organ hypoperfusion.”
  3. *Sub-lingual nifedipine is very strongly contra-indicated (11, 16-18). It can result in uncontrollable hypotension and hypo-perfusion which may cause stroke or sudden permanent blindness. Indeed some experts have suggested instant/rapid-release formulations of nifedipine should be prohibited(5, 19) and that it should never be given to patients to self-administer.


1.         McCormack, D and Buckley, N, Psychostimulant poisoning. Australian Prescriber, 2006. 29: p. 109–11.


2.         Murray, L, Daly, F, Little, M, and Cadogan, M, Toxicology handbook. 2011: Elsevier Australia.

3.         Grossman, E, Nadler, M, Sharabi, Y, Thaler, M, et al., Antianxiety treatment in patients with excessive hypertension. Am. J. Hypertens., 2005. 18(9 Pt 1): p. 1174-7.


4.         Yilmaz, S, Pekdemir, M, Tural, U, and Uygun, M, Comparison of alprazolam versus captopril in high blood pressure: a randomized controlled trial. Blood Press., 2011. 20(4): p. 239-43.


5.         Grossman, E, Messerli, FH, Grodzicki, T, and Kowey, P, Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA, 1996. 276(16): p. 1328-1331.

6.         Messerli, FH and Eslava, DJ, Treatment of hypertensive emergencies: blood pressure cosmetics or outcome evidence? J. Hum. Hypertens., 2008. 22(9): p. 585-6.


7.         Chobanian, AV, Bakris, GL, Black, HR, Cushman, WC, et al., Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension, 2003. 42(6): p. 1206-52.


8.         Chou, C-L, Chou, C-Y, Hsu, C-C, Chou, Y-C, et al., Old Habits Die Hard: A Nationwide Utilization Study of Short-Acting Nifedipine in Taiwan. PloS one, 2014. 9(3): p. e91858 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091858.

9.         Gemici, K, Baran, I, Bakar, M, Demircan, C, et al., Evaluation of the effect of the sublingually administered nifedipine and captopril via transcranial doppler ultrasonography during hypertensive crisis. Blood Press., 2003. 12(1): p. 46-8.


10.       Ishibashi, Y, Shimada, T, Yoshitomi, H, Sano, K, et al., Sublingual nifedipine in elderly patients: even a low dose induces myocardial ischaemia. Clin. Exp. Pharmacol. Physiol., 1999. 26(5-6): p. 404-10.


11.       Bulling, M and Burns, R, Occipital cortical "angina" induced by nifedipine. Med. J. Aust., 1988. 148(5): p. 266.


12.       Morton, C and Hickey-Dwyer, M, Cortical blindness after nifedipine treatment. BMJ, 1992. 305(6855): p. 693.


13.       Marik, PE and Rivera, R, Hypertensive emergencies: an update. Curr Opin Crit Care, 2011. 17(6): p. 569-80.


14.       Flanigan, JS and Vitberg, D, Hypertensive emergency and severe hypertension: what to treat, who to treat, and how to treat. Med. Clin. North Am., 2006. 90(3): p. 439-51.


15.       Migneco, A, Ojetti, V, De Lorenzo, A, Silveri, NG, et al., Hypertensive crises: diagnosis and management in the emergency room. Eur. Rev. Med. Pharmacol. Sci., 2004. 8(4): p. 143-52.


16.       Feldstein, C, Management of hypertensive crises. Am. J. Ther., 2007. 14(2): p. 135-9.


17.       Marik, PE and Varon, J, Hypertensive crises: challenges and management. Chest, 2007. 131(6): p. 1949-62.


18.       Schwartz, M, Naschitz, JE, Yeshurun, D, and Sharf, B, Oral nifedipine in the treatment of hypertensive urgency: cerebrovascular accident following a single dose. Arch Intern Med, 1990. 150(3): p. 686-7.


19.       Burton, TJ and Wilkinson, IB, The dangers of immediate-release nifedipine in the emergency treatment of hypertension. J. Hum. Hypertens., 2008. 22(4): p. 301-2.