Adverse Effects of Suddenly Stopping a Medicine
By Marcus M. Reidenberg, MD, FACP
Weill Cornell CERT
Summary by Kathleen Mazor, EdD
HMO Research Network CERT
People with chronic illnesses often have to take medicines for a long time. Most people occasionally skip doses. For example, 50% of patients treated for high blood pressure in a long term study delayed one or more doses a month of a once-a-day medicine for over 30 hours. In fact, 10% of the patients delayed 2 or more doses per month for over 2 ½ days (1). Other studies show that medicines that effectively treat cardiovascular disease are frequently just stopped by the patient (2).
Unfortunately, this abrupt discontinuation of a medicine can have adverse consequences. The reason is that medicine withdrawal effects are common for medicines taken over a period of time. Some of these effects are rebound high blood pressure when antihypertensive medicines are suddenly stopped, heart attacks when daily low doses of aspirin are stopped, and unstable angina when calcium channel blockers like verapamil or beta adrenergic blockers like propranolol or atenolol are stopped (3). Sometimes these withdrawal effects can be fatal.
Many medicines in other therapeutic classes have withdrawal effects if abruptly stopped after continuous use. These include adrenal steroid medications like prednisone and estrogens (4) and all of the antidepressants medications (5, 6). Even some babies born of mothers taking some antidepressants toward the end of pregnancy can have a withdrawal effect during their first week of life (7). Abrupt cessation of long-term tamoxifen can cause mood changes (8).
Thus, abrupt cessation of many medicines in addition to those that are subject to abuse can have withdrawal effects.
The reason can be explained in broad terms. When a medicine is taken in adequate dose for a period of time, the body adapts or adjusts to it. Some part of the body changes. When the medicine is discontinued, it leaves the body before this change goes back to the way it was before the medicine was started. This persistent change in the body in the absence of medicine is what causes the withdrawal effects.
In time, and in the absence of the medicine, the change in the body subsides and with its disappearance, the withdrawal effects also subside. The time all this takes varies with the medicine and the person.
Much more research is needed into the details of medicine withdrawal reactions and how best to manage them. This is a subject that has been neglected in much of medical research.
One should realize that symptoms which occur within a few days of abruptly stopping a medicine that has been taken for a while may be due to an effect of abruptly discontinuing the medicine. For some medicines used to treat heart disease, this effect can be a heart attack. These cardiovascular medicines should really be taken continuously and not skipped for several days at a time. If these medicines are to be discontinued, it should be done as advised by a doctor.
- Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories BMJ. 2008 May 17;336(7653):1114-7.
- Andrade SE, Walker AM, Gottlieb LK, Hollenberg NK, Testa MA, Saperia GM, Platt R. Discontinuation of antihyperlipidemic drugs--do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med. 1995 Apr 27;332(17):1125-31.
- Reidenberg, MM. Drug discontinuation effects are part of the pharmacology of a drug: Cardiovascular drug discontinuation syndromes. J Pharmacology Exp Ther. submitted.
- Hochberg Z, Pacak K, Chrousos GP. Endocrine withdrawal syndromes. Endocr Rev. 2003 Aug;24(4):523-38.
- Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998 Jul 15;44(2):77-87
- Garner EM, Kelly MW, Thompson DF. Tricyclic antidepressant withdrawal syndrome. Ann Pharmacother. 1993 Sep;27(9):1068-72.
- Laine K, Heikkinen T, Ekblad U, Kero P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry. 2003 Jul;60(7):720-6.
- Kerr B, Myers P. Withdrawal syndrome following long-term administration of tamoxifen. J Psychopharmacol. 1999 Dec;13(4):419
This note can be found online at http://www.weill.cornell.edu/cert/patients/suddenly_stopping_medicine.html
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