Over-the-Counter Ibuprofen: A Reversible Cause of Hypertension and Headache

The patient is a 47-year-old man who began to experience frequent headaches about 6 years before he presented to a neurology clinic. The headaches rapidly progressed to become daily and almost constant. He described a sensation of dull pressure in both temples that was present on or within a few hours of awakening and that persisted for the remainder of the day. He experienced a more intense, disabling, throbbing pain in the same location once or twice a week, with photophobia and nausea, that might last 2 to 3 days. The patient took 2 to 6 over-thecounter (OTC) analgesic tablets each day—usually 200 mg of ibuprofen. These would dull but not terminate the pain.
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Six months after the onset of these headaches, the patient sought care from a primary physician, who diagnosed mild hypertension (blood pressure, 140/102 mm Hg). Results of a 24-hour urinalysis for catecholamines and an MRI scan of the head were normal. The patient was referred to a neurologist, who reported that the neurologic examination was normal and that the diagnosis was tension-type headache; that doctor prescribed amitriptyline, 10 mg hs. The patient stopped taking the medication after a few weeks because of side effects, however. The primary physician thought that the hypertension was causing the headaches, and prescribed 50 mg/d of atenolol. Despite this therapy, the patient continued to experience daily headaches for the following 5¹/₂ years.

During that 5¹/₂-year interval, the patient returned periodically to the primary care physician; he also checked his blood pressure frequently at home. Most blood pressure recordings were normal, but elevations as high as 160/ 110 mm Hg occurred whenever he omitted the antihypertensive medication for a day or two. There was no change in the pattern of the almost constant headaches with these elevations of blood pressure. His daily consumption of analgesics continued. Five years later, nifedipine, 30 mg/d, was added to the regimen. This agent did not change the headaches, but it did reduce the blood pressure. In previous years, the patient had infrequently experienced typical episodic tension-type headaches that might start in the afternoon; these could be quickly terminated with 1 or 2 tablets of an OTC analgesic. He also experienced an occasional isolated migraine without aura. The medical history was otherwise noncontributory. The patient was unaware of any elevations of blood pressure before his initial visit to the primary physician.

He was referred to the Vanderbilt Headache Clinic with this 6-year history of almost constant headaches with superimposed migrainelike attacks for which he had used 4 to 6 analgesic tablets daily. The history was reviewed; results of his neurologic examination were normal. Blood pressure was 90/62 mm Hg in the right arm and 90/ 68 mm Hg in the left. Rebound headache was suspected.

The phenomenon of rebound headache was carefully explained to the patient. He was told that until proved otherwise, the headaches of 6 years’ duration were the result of the almost daily use of pain relief medications. He was given a list of analgesics (aspirin, acetaminophen, NSAIDs, opiates, ergotamine, triptans, and caffeine) to avoid completely. He was also told to stop the antihypertensive agents and to monitor his blood pressure frequently at home. Finally, he was asked to keep a headache calendar and to return to the clinic in 4 weeks.

After the forbidden pain relief medications were totally omitted, the patient’s headaches gradually subsided. After 3 weeks, he had the onset of 12 consecutive days of total freedom from pain. At that time, he was told to limit analgesics to 2 days per week in the future. More frequent use of analgesics might result in recurrence of the chronic daily headache and the hypertension.

During the following 5 years, the patient’s blood pressure remained normal without the antihypertensive agents, except for a single recording of 148/94 mm Hg during the fifth month. He had infrequent, brief, tension-type headaches, but no daily headaches and no migraines. He seldom used an analgesic during this 5-year interval.

When encountering a patient with new-onset hypertension, the physician needs to obtain a complete history, perform a thorough examination, and order appropriate laboratory studies to try to determine the cause. Often, a specific cause for the blood pressure elevation cannot be found and the patient is labeled as having essential, or primary,hypertension. He or she is then given long-term antihypertensive therapy with the hope that the pressure will become lower and its complications will be reduced or delayed.

Many physicians do not realize that daily OTC analgesics—especially NSAIDs—can cause secondary hypertension.^1-3 If the analgesics are not stopped, the blood pressure may remain elevated for months or years. Likewise, many physicians are not aware that the most common cause of chronic daily or almost daily headaches is the daily or almost daily use of medications for symptomatic relief of headache pain.⁴ The case history presented here documents how the failure to recognize these possibilities resulted in a patient having 5¹⁄₂ years of daily prolonged headaches and taking unnecessary antihypertensive medications.

REBOUND HEADACHE

Rebound headache—also called chronic refractory headache, chronic migraine, transformed migraine, and a host of other names—typically presents as a constant, dull, tension-type headache with frequent superimposed more intense migrainelike attacks.⁵ The patient uses pain relief medications daily or almost daily that only dull or briefly stop the pain.

Medications to prevent headache are ineffective when a patient is in the rebound state. Some patients can recall a specific illness, operation, or injury for which they initiated the daily medications. Many, however—especially those with a prolonged history of headache—cannot recall a specific precipitating event: these patients might describe a sudden or gradual development of daily headache.

This patient’s story was typical for rebound headaches— a condition that can be suspected from the history and proved only by the delayed termination of the daily headaches after total omission of all pain relief medications that might cause this problem (namely, aspirin, acetaminophen, NSAIDs, opiates, ergotamine, triptans, and caffeine). No laboratory test points to this diagnosis. The offending medications must be avoided until the goal of 6 consecutive pain-free days is reached. Although some patients note cessation of daily headache in 1 week, the mean time for patients to experience 6 consecutive painfree days is 3 months.⁵ A few patients might not reach this goal until the 12th month or later.

This patient’s hypertension was not identified until after he had used OTC analgesics for 6 months. There have been many other patients seen in our tertiary headache clinic in whom hypertension developed after the use of NSAIDs and in whom blood pressure returned to normal after daily analgesics were discontinued.

WHICH CAME FIRST: HYPERTENSION OR HEADACHE?

Physicians often fail to inquire or consider which came first, the blood pressure elevation or the frequent headaches. In 1953, Stewart6 documented that hypertension alone rarely causes headaches unless the systolic pressure is over 200 mm Hg and the diastolic pressure exceeds 120 mm Hg.

In the past 15 years, numerous articles have stressed that analgesics—especially NSAIDs—can cause mild elevations of blood pressure^3,7-11 or affect the control of preexisting hypertension.^3,8 The mean elevation of systolic pressure is often only 5 mm Hg⁹ and varies between the nonselective NSAIDs. Ibuprofen is less likely to cause elevations of pressure than piroxicam, indomethacin, naproxen, celecoxib, or rofecoxib.³ The Nurses Health Study reported that the risk of hypertension was slightly greater in women who were using acetaminophen 22 or more days per month than in those using NSAIDs 22 or more days per month.¹⁰ Aspirin is occasionally cited as a cause of minimal elevations of blood pressure. One article describes the case of an elderly patient using salsalate in whom hypertension developed.¹¹

In short: essentially all analgesics can elevate blood pressure in some persons. The mechanism is not fully understood.

When one looks at the chapters on hypertension in recent textbooks of medicine, NSAIDs are included in the lists of agents that cause secondary hypertension; however, this cause of hypertension is not stressed in the accompanying text.^1,2 In the most recent edition of a popular textbook of family practice, NSAIDs were not included in the list of drugs causing this problem.¹² It is not surprising that the busy practitioner might be unaware of this problem.
When confronted with a patient with new-onset hypertension, clues that suggest secondary hypertension and rebound headache include a history of headaches that began before the onset of hypertension; blood pressure of less than 200/120 mm Hg in a patient with daily headache; and daily tension-type headaches with intermittent migraine attacks that start when the patient awakens or shortly thereafter and that persist most of the day.

Frequent consumption of OTC ibuprofen is a cause of hypertension and of chronic daily headaches. Both can be reversed by discontinuing the drug.