VOLUME 79 NUMBER 2’ AUGUST 1985

The American Journal of fVkdicines

Polypharmacy Causes, Consequences, and Cure

KURT KROENKE, M.D., Maj., M.C.

The desire to take medicine is perhaps the greatest feature which distinguishes man from animals.

Sir William Osler

o startle his audience into thinking, Osler could ex- T aggerate. His anthropologic overstatement about medication is one example. Beneath his hyperbole, however, lies humanistic insight, an ability to recognize and describe the foibles of humans. Homo sapiens is certainly more than a taker of pills. Yet to drive out an inner affliction with an external remedy has occupied and preoccupied the species. Ingestion, injection, in- halation, internalization in sundry forms: all have been utilized for centuries to heal. Although variably suc- cessful, pills and potions and pharmaceuticals have radiated an almost mystical aura. Therein, for example, lies the placebo’s power. Patients so strongly desire a tonic that they transcend the organic facts. Charisma is added to the chemistry of a medicine. The physic becomes metaphysical. Additionally, it is presumed, more must be better. If one pill is palliative, two might be purgative, and three, a potential panacea. Poly- pharmacy isthe outcome. Bottles proliferate. The drive to eliminate discomfort encourages the expansion of therapeutic regimens. The human’s “desire to take medicine” carries, however, a price tag. Nature’s maladies are succeeded by iatrogenic hazards. Arising out of a restorative instinct, polypharmacy becomes itself an affliction. As such, it is worthwhile to examine its causes, its consequences, and its cure.

CAUSES

Polysymptoms. “Many are the afflictions of the righteous” (Psalms 34:19). Suffering is often plural. When one symptom performs, more await backstage.

A problem list of one is unusual. Illnesses are gregar- ious. Hypertension is frequently accompanied by a permutation of diabetes, emphysema, angina, and ar- thritis. These are the “real” diseases. Many patients present with anonymous pain, with ailments nosologi- tally incomplete. Although their suffering cannot be categorized into chapters of a textbook, they too seek relief. Furthermore, functional disease, like organic, can be manifold. The patient with multiple complaints, the somatisizer, the hypochondriac, beleaguers the phy- sician for prescriptions. Hence, the number of symp- toms, be they real or imaginary, is a powerful correlation of the number of medications. Obesity is familial. Where the problem list is fat, the therapeutic regimen it en- genders grows corpulent. Polyphysician. Where physicians gather, opinions gather likewise. Doctors make poor fellow travelers. Confronted with a single disease, one will take the therapeutic high road whereas the other will select the low road. Although arriving at the same destination, they choose alternate routes. The patient consulting several pilots thus accumulates road maps. Like cooks in a kitchen or generals in a war, doctors may interfere with each other in close quarters. The ideal physician-patient ratio is often 1. Does that mean there is no room for consultation or for the management of distinctive problems by different specialists? Cannot each respect the other’s turf? Probably so, but still there needs to be a head coach, a pharmaceutical gatekeeper controlling the patient’s regimen. Where multiple voices cry out, one doctor must moderate the assembly. Herein, communication is crucial. For one doctor to make fur- tive and repeated therapeutic alterations is both an in- considerate and a dangerous practice. Prescribing in

From the Department of Medicine, Brooke Army Medical Center, San Antonio, Texas. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Requests for reprints should be addressed to Dr. Kurt Kroenke, Box 523, Beach Pavilion, Fort Sam Houston, Texas 78234.

August 1985 The American Journal of Medicine Volume 79 149

EDITORIAL---KROENKE

a vacuum produces medication lists that are not only adipose but at times even hazardous to health. Novelty. As Osler distinguished man from lower species by his pill-taking fervor, so we may, in another vein, characterize human beings by their proclivity for the new. Fads are ubiquitous. Whereas most organisms are seekers of patterns, homeostatic, instinctual, hu- mans are explorers. A modern commercial exhorts the consumer to “try it-you’ll like it.” The frontier beckons. From the Charleston to break dancing, from the hula hoop to Cabbage Patch dolls, change is continual. Hence, the advent of a drug is heralded like a new kid on the block, with the patient anxious for introduction, for a trial run of friendship. Increasing this urge is the failure of prior regimens. Illness often defies us. Viruses, cancer, chronic diseases frustrate our therapeutic machismo. The new is anticipated most when the old has least succeeded. As long as change attracts hu- mans and disease eludes cure, novelty shall remain a potent incentive to prescribe. Habit. Although the new may be enticing, old friends are not abandoned easily. Humans are both revolu- tionary and reactionary animals. One side of their nature seeks the excitement inherent in change; the other clings to the security and stability of custom. Deleting a medicine is like severing a therapeutic umbilical cord. A maxim might be stated: once prescribed, eternally refilled. Thyroid extract begun years ago for fatigue, or digoxin initiated for nonspecific dyspnea, is not easily relinguished merely because modern radioimmunoas- says and echocardiography disprove the physiologic necessity of these medications. Novelty is the attraction of a new medicine. Habit is our allegiance to the old. Placebos. The pressures to prescribe are numerous. First, the patient wants pills. A visit to the doctor is ac- companied by expectations of medication. Second, there is an economic corollary. The physician com- mands a handsome fee that he is reluctant to collect without some overt therapeutic act. Advice seems in- sufficient. Laying on of hands or, in lieu of this, dis- pensing a nostrum, justifies remuneration. Third, time is a constraint. Explanation moves more slowly than prescription. The decision to forgo medication requires a lengthy statement of defense or even apology. To convince the patient that antibiotics are ineffective for a cold may require more time than we are willing to expend. Fourth, physicians have a professional as well as a personal inspiration to heal. Whether as doctor to patient or as human being to human being, the clini- cian’s longing to alleviate pain is intense. These pres- sures to prescribe-expectative, economic, expedi- tious, and humanistic-promote placebo ministrations. Placebos should not be pejoratively dismissed. Their power to palliate and even to heal can be considerable. With many illnesses, effective treatment is lacking. In

other cases, such as antihistamines in colds and vita- mins for fatigue, one’s use of medications is nonspe- cific. The efficacy and the ethics of such utilization are separate issues. What is clear is that the incorporation of optional and nonspecific medicine inflates a patient’s regimen. Polypharmacy ensues. Pressures to prescribe must be weighed against the risks of liberal prescrip- tion. Generalization. Indications expand exponentially. A drug is investigated and eventually approved for specific reasons. But the Food and Drug Administration is soon forgotten. A medication introduced for special situations becomes a drug for all seasons. What results is the foot-in-thedoor phenomenon. A drug proved effective for active ulcers gains widespread use for indigestion. Expensive antibiotics, more appropriate in reserve, become first-line therapy for ambulatory infections. A costly diuretic of potassium-sparing fame is routinely prescribed, regardless of electrolyte levels. As in contemporary sports, the rookie replaces the veteran, and at a much inflated salary. Salesmanship. Prescription is more than a triad. Forces external to the doctor, the patient, and the illness are at work. Three additional agents endeavor to influ- ence and extend drug utilization. These salesmen in- clude the drug detail man, acquaintances, and the media. The first works on the doctor, using visits to the clinic, free lunches, brochures, favorable reprints, coffee cups and penlights inscribed with the new drug’s name. Friends meanwhile plant the seed in the patient. Having gotten the drug themselves or having heard about it, read about it, or thought about it, they pique the patient’s curiosity. Sometimes they go so far as to let the patient sample one of their own pills. This phar- maceutical grapevine permeates the lay community. Finally, the media pressures both doctor and patient. A nightly news program hails a drug, another nonster- oidal agent, as a miracle treatment for arthritis. A tabloid cover story depicts the latest beta blocker as heart disease’s cure. A patient unfolds a newspaper clipping that relates the “new” treatment for hypertension and asks, “Why haven’t you thought of this, Dot?” The drug companies, the media, and the lay community add fuel to the flames of polypharmacy.

CONSEQUENCES

Potluck. A common consequence of too many pills is organizational breakdown. Given a regimen of four pills once a day, one pill twice a day, three pills three times daily, and two pills four times daily, compliance suffers. Even the best intentions struggle under such complexity. Day-today pill-taking becomes a little like a church dinner, at which no one takes exactly the same foods or the same portions. An assortment of dishes bewilders the senses. Except for the most compulsive

150 August 1985 The American Journal of Medicine Volume 79

patient, a regimen of many pills many times a day breeds more variety than regularity. Reducing pills and reducing intervals helps minimize the randomness of taking drugs. Potluck becomes a balanced diet. Dyspepsia. The more the drugs, the more the drug- drug interactions. Where medicines abound, side effects may flourish. It is a numbers game. Each drug has a small but real potential of causing harm. Increase the drugs and the potential of harm increases. This is mere addition, an arithmetic increase. Where drugs interact, where adversity is synergistic, the increased risk is geometric. A bloated regimen results in therapeutic reflux. Heartburn is reduced by smaller feedings. Duplication. Dyspepsia describes a clash of arms, a consequence of opposing armies. At times, however, one’s own forces are overstrengthened. Because of multiple physicians or because of hoarding old bottles or because of desiring the new while simultaneously clinging to the old, patients accumulate related drugs. The patient with several antihistamines, the regimen containing multiple psychotropic drugs, the arthritic sufferer taking redundant analgesics-these are but a few examples. As with the military in the aftermath of a war, a reduction in forces becomes necessary. Like the overweight guest selecting desserts who exclaims, “I’ll take one of each,” the prescription-heavy patient does not need the extra calories. Dilution. Strength in numbers does not apply to medication lists. Important drugs may drown in flooded regimens. Commonly, a drug with clear-cut indications is surrounded by less specific cohorts. A hypertensive patient’s diuretic competes with acronyms less critical, like OTC (over the counter) and PRN (take as needed). A pill to regulate blood glucose levels gets lost among the diabetic patient’s decongestants, analgesics, lax- atives, and vitamins. Taking pills becomes a little like a state lottery. The vital drug is only one of many num- bers. Its chance of being drawn a given day is dimin- ished by superfluous entries. Dilution is a consequence of liberal prescription. Placebos, pills to be taken epi- sodically, drugs of unproved value, stand side by side with medicine needed three times daily. Appearances further confound the matter. Optional and required pills are similarly clothed: regulation brown bottles, child- proof caps, the pharmacist’s official label. The drugs themselves are equally impressive-various colors, multiple shapes, different sizes, capsules, tablets, liq- uids. Once dispensed, a medicine acquires status. Polypharmacy results in too much class. Dust. Attics are nostalgic storerooms wherein sen- timent accumulates in various forms: broken toasters, magazines, unfashionable clothes, a retired crib, abandoned toys. A medicine cabinet is a kind of attic in which old prescriptions assemble longitudinally on shelves. In this museum of prior symptoms, a patient’s

EDITORIAL-KROENKE

medical history unfolds. Former medications, diseases, and physicians may be perused. Diuretics past and present are preserved, their labels demonstrating the natural history of a regimen: “Hydrochlorothiazide 50 mg 1983”; ” Furosemide 20 mg 1984”; “Furosemide 40 mg 1985.” The dangers are apparent. What is cur- rently being taken is not clear, even at times to the patient. There is a risk of taking old, ineffective medi- cation, or worse, a combination of similarly acting drugs. For example, all three diuretics just listed might be in- gested, producing diuresis in triplicate. The potential morbidity of taking multiple hypoglycemic agents, antiarrhythmic drugs, or tranquilizers is even greater. Some people are notorious collectors, unable to throw anything away. This is an unwise practice when applied to medications and should always be considered in patients exposed to polypharrnacy. If dust has settled on a bottle since last being opened, disposal may be overdue Amrresia. Medicines are difficult to recollect. Indeed, a dyslexia regarding labels seems to pervade the public. Patients remember faces but not names. “Little white pills” are the item most reported on medication in- ventories. Polypharmacy exaggerates amnesia. Al- though one pill might be recalled, the names of addi- tional drugs may saturate cerebral receptors. The therapeutic regimen becomes an anonymous assort- ment of colors, sizes, and shapes. Frequencies are forgotten as well. When questioned as to how many times a day a medicine is taken, the patient hedges by saying, “It’s on the bottle.” Noncompliance seems likely. Multiple intervals multiply the problem. Imagine a patient assigned to a capsule three times daily, a bronchodilator to be inhaled as two puffs every four hours, a pill at bedtime, insulin injections before breakfast and supper, a morning dose of digitalis, and various analgesics, creams, and laxatives to be used as needed. Such a regimen is common and serves ad- ditionally as a test of mental status. The patient who recollects its intricacies need not proceed with serial sevens.

CURE

Given the unfortunate consequences of polypharmacy, is there any cure? How can one cope with the pressures to grant new medication? How can one deal with the patient already receiving many drugs? A five-step ap- proach will be considered. Seeing. Our opening admonition to the patient should be, “Bring your bottles,” for what we hear is seldom what the patient gets. A verbal account is like a foreign poem translated: we capture only half the meaning. Medicines are forgotten, or remembered wrongly. Names are deleted or distorted. Dosages and dosage intervals are incorrect. The brown bag approach, therefore, is the appropriate beginning. Instruct the

August 1985 The American Journal of Medicine Volume 79 151

EDITORIAL-KROENKE

patient to clear his or her shelves of every pharma- ceutical, bag them, and bring them in. Lined up on your desk, the problem can be viewed in its entirety. Friends and foes and neutral factions can be distinguished; conventional battle lines drawn; guerilla warfare avoided. Seeing the medicines clears the ground for change. Sorting. Faced with many bottles, how does one proceed? In a single word: “prioritize.” Symptoms are not created equal. The pain of angina is more important than chronic low back pain. The disabilities may be commensurate, but the threat to life is clearly not the same. In short, the heart medicine takes precedence over the pills to soothe the back. Diabetes is more se- rious than constipation. Hence, the drug to regulate blood glucose levels ranks higher than the one to reg- ulate the bowels. Again, we’re emphasizing future prognosis, not present distress. This is not to say the latter can be ignored. Indeed, the dismay resulting from constipation may surpass that caused by hyperglyce- mia. The palpitations of anxiety may produce morbidity greater than that of nonsustained ventricular tachy- cardia. Hyperventilation may lead to emergency room visits outnumbering those of hypertension. Physicians need to address both the real diseases and the per- ceived illnesses of their clientele; the external abnor- malities as well as the internal malaise. Communication is therefore paramount. Doctors must both hear and speak. They first must listen to the patient’s wants. Following a systematic collection and review of all the data, they then must inform the patient of serious, albeit silent, needs. Having identified both wants and needs, they proceed at last to therapy. Sometimes reassurance alone suffices. At other times, nondrug therapy can be conSidered, including diet, exercise, relaxation, and abstention. Finally, medications have their place. Realizing the consequences of excessive medicine, however, one can selectively prescribe. Two questions should be foremost. What objective findings may result in eventual morbidity? What subjective complaints are causing greatest distress? Answering these will limit the use of optional, trivial, and placebo medication. The chaff excluded, the therapeutic wheat may grow to greater heights. Stopping. The patient often comes with many friends. Therapeutic virgins are uncommon. Presented with a person taking numerous pills, what does one do? The first precaution simply is-go slow. Ultimately, it is nice if unimportant drugs can be phased out. Several prin- ciples facilitate attrition. First, never stop a drug on the first visit. To wean a patient away from an old allegiance requires formation of a new one. A therapeutic alliance, a doctor-patient bond, must be established, and this takes time. Let several visits pass before the issue of

eliminating drugs is broached. Second, discontinue inch by inch. A rule of thumb might be to stop no more than one drug at a time, and this one slowly, over time. Consider tapering. Gentle braking may be preferable to sudden stops. A pill that is taken twice a day may be reduced to once a day; a 50 mg dose cut in half. On subsequent visits, if all goes well, deletion can be completed. Patience and ongoing communication are the keys. Listening to the patient’s uncertainties, sep- arating mere anxiety from symptoms caused by medi- cation withdrawal, can enhance the prospects of suc- cessful drug deletion. Polypharmacy is best attacked by siege and not by storm troops. Starting. Habits not acquired need not be broken. The easiest way to avoid tobacco is to never take up smoking. Physicians are more effective gatekeepers at the entrance than at the exit of a patient’s regimen. Initiate drugs niggardly. As mentioned, “prioritize” the patient’s symptoms. Be hesitant to prescribe for minor, nonspecific, or self-limited complaints. Stress that medication offered for such conditions is temporary, and not intended as a permanent addition to the medicine cabinet. Counsel against excessive reliance on over- the-counter drugs. Limit the use of PRN-“take as needed”-pills. Both of these dilute the patient’s es- sential regimen. Think twice before dispensing a non- specific pill for a nonspecific symptom. Medicine dis- pensed for a short term may insidiously become long- term. Prescription is a solemn task. Its casual and len- ient practice should be discouraged. Simplifying. Prescription is nevertheless an ancient and essential task. Nostrums have been administered as long as humans have claimed healing powers. Once we have attained the essential regimen, purged of all that is dross, a final task remains. The regimen should be sculptured to its simplest form. Carve away unnec- essary edges, redundant stone. Reduce the regimen to the fewest drugs, the fewest quantity of pills, the fewest dosage intervals practical. Can a medicine taken four times daily be given twice a day at a higher dosage? Can a single drug suffice for two? Can medications be given at the same time (for example, three drugs, each twice daily) rather than scattered throughout the day (that is, drug A once a day, drug B twice a day, drug C three times daily)? Plan the scheduling of drugs around the patient’s schedule, not vice versa. The inconspicuous regimen is best, the one that intrudes on work and play the least. Camouflage the time for taking pills so that it blends in with the rest of life.

I have suggested seven causes, six conse- quences, and a five-step cure for polypharmacy. This essay is not exhaustive. At best, it may serve as sand to irritate the oyster. Pearls to purchase better pre- scriptive habits may then ensue.

152 August 1995 The American Journal of Medicine Volume 79