Polypharmacy: When too much good is no good!

Introduction:

While medications from the time of antiquity have saved lives and do so more and more over time, have fostered health and increased longevity, too many medications or polypharmacy, particularly if it is not necessary, could cause more harms than benefits. Polypharmacy is seen in all age ranges and in all countries, but more in patients with comorbidities or more than one medical conditions, specially in the older population that is more risky and cause more harms and is more common in developing countries. Although it is assumed commonly that polypharmacy is used in comorbidity conditions, one would be surprised that it is common as well in single medical conditions, when physicians helplessly add to the number of medications to bring under control a non-responsive medial condition. (1-3)

 

The common and known unfavorable effects or harms of polypharmacy are adverse drug reactions, drug-drug interactions, low adherence to drug therapy and stopping all the medications by the patient, psychological dependency of the patient that only medications could help so not to resort to non-pharmacotherapy modalities if available, also physical dependency if the medication (s) are addictive, and finally the burden of the body tissues and organs by too many medications as foreign objects, specially on liver and kidneys that mostly metabolize the medications. In addition, it is also assumed that polypharmacy causes unnecessary health expenditure, directly due to redundant drug sales and indirectly due to the increased level of hospitalization caused by drug-related problems. Drug-related problems are reported to cause a substantial proportion of all emergency treatment and admissions to hospitals such as in elderly population. (4-7)

 Unfortunately many studies of polypharmacy have primarily been conducted on samples of elderly individuals admitted to hospitals or nursing homes, and only a few have been population-based studies, though some of these again have also been limited to elderly individuals. A recent register study showed that 2/3 of all individuals in a national population who were being prescribed with 5 or more drugs were < 70 years of age, indicating that multiple medication use is not only common in elderly population. A recent Swedish Prescribed Drug Registery in the period of 2005-2008 has shown an 8.2% increase in polypharmacy (>5 medications). (8-9)

In this article, we discuss first polypharmacy in different age groups, elderly, adults, children and adolescents, then across a few common medical disciplines, among comorbidities and single medical conditions.

 

Polypharmacy across life span:

In the above mentioned Swedish study of polypharmacy between 2005-2008, the prevalence of more than one medication in elderly (>70) was 80% on average, with more than 5 drugs averaged 45%, and more than 10 medications was about 13% on average. In adult age group, the prevalence of more than one medication was 30-40% in the age range of 20-49, but that jumped to > 50% in 50’s and to about 65% in 60’s. The use of more than 5 and 10 medications were rare until the 5th and 6th decades of life that was about 10% and 20%, but the use of more than 10 medications was still rare. In children and adolescence surprisingly the use of more than one medication was quite high about 18% in the first decade and 22% in the second decade of life. The number of individuals on polypharmacy and excessive polypharmacy over 5 medications were quite high, >4,500 in the first decade of life, >9,000 in the second, about 18,000 in the third, >35,000 in the fourth, close to 70,000 in the fifth, >138,000 in the sixth, >220,000 in the seventh decade of life, and in the elderly, 70-79 years old it was close to 250,000 and in the 80-89 years age group, it was >210,000. Surprisinlgy in all age groups the prevalance of polypharmacy has been increasing over years from 2005-2008. (9)

 The polypharmacy in the age group 0-9 years was more related to the prescription of antibiotics to children, and nearly 80% of these children received antibiotics in 2006. (8) The reason behind the increase in polypharmacy over years in other age groups, while puzzling, it seemed to be more due to relatively rapid changes in prescription patterns among prescribers, mostly due to the introduction of new clinical guidelines.

Prior to 2005, national clinical guidelines were available for only three different medical conditions in Sweden, while during the study period, 2005-2008, The National Board of Health and Welfare in Sweden introduced four new national clinical guidelines, and in 2009-2011 seven more new clinical guidelines, making it a total of 14 until 2011. In a study from Sweden concerning general practitioners’ (GPs’) perceptions of multiple-medicine use, clinical guidelines were viewed as “medicine generators”. GPs’ expressed frustration concerning guideline recommendations for certain diagnoses, e.g. cardiovascular diagnoses that “immediately result in five medicines”. (10)

Polypharmacy across medical illnesses

In comorbidities:

As the number of illnesses of a person increases, also the age, the number of medications may increase. This is not only limited to the prescribed medicines, but over-the-counter (OTC) medications that by many presumed to be natural and not chemical, so it is ok to take them. Among comorbidities, cardiovascular diseases take on about 60% of the polypharmacy, while nervous system specially psychiatric ailments take on close to 40%, GI (Gastrointestinal) and metabolic diseases such as diabetes are the third in the row with over 33%, followed closely by blood diseases about 30%, musculo-skeletal system about 18% and respiratory illness about 12%. (11)

 Among the medications, antithrombotic agents are on the top of the list mostly in elderly with about 30%, lipid modifying agents are second with about 28%, followed by beta blocking medications with 24%, peptic ulcer and reflux diseases agents with about 15%, anxiolytics mainly benzodiazepines or tranquilizers with >13%, followed closely by the selective calcium channel blockers with mainly vascular effects with <13%, ace inhibitors >11%, antidepressants <11, NSAIDs (non-steroidal anti-inflammatory) products, and hypnotics and sedatives both around >10% of all polypharmacy prescription and usage. In summary cardiovascular medications comprise about 80% of all polypharmacy, followed by psychiatric agents with about 36% are the most common over-used and over-prescribed of all medicines. (11)

 

In single diseases:

Cardiovascular diseases, specially in the elderly as shown in the above statistics, take on the most of polypharmacy, that could be simply for the treatment of one condition such as hypertension, or for the prevention of complications such as heart attacks. Other than this which is obvious in the elderly population and is mostly initiated by the physicians and not the patients, there is polypharmacy in pain management that is caused both by the prescribers and the patients. Among the analgesics, the opioid analgesics mostly morphine, codeine and methadone products alone or in combination with pure analgesics such as acetaminophen or Tylenol have become an increasing epidemic. Such a rate of use has almost doubled from 5% in 1997 to 9% in 2005 in US, causing over 33,000 deaths per year, and abused as taken from multiple prescribers by the patients who have become addicted to these products. (12-13)

 The reasons for polypharmacy are two-sided on the physician or prescriber and the receiver or the patient part. One trigger is the helplessness on either or both sides in a strive to control or treat a non-responsive medical condition. The other common reason for polypharmacy is symptomatic treatment that is not treating the cause of the illness, but the symptom(s) that often is like shooting in the dark, ending shooting many shots until one hits the target that often is missed. This common reason is applied often in the pain management that commonly targets the reception of the pain by the central nervous system or mainly the brain, and not treating the initial pathologic cause or locus of the pain.

 

Other than the pain management that causes unnecessary polypharmacy, psychiatric treatments are often include such multi-medications prescription, partly for symptomatic treatment or shooting in the dark, or out of helplessness of treating a non-responsive condition. Polypharmacy has become a common clinical practice for many psychiatric conditions, so much up to one-third patients visiting outpatient psychiatry department have been found to be on three or more psychotropic drugs. (14-15) Monotherapy in psychiatry from 48% before 1980, has declined to 31% between 1981-1990, and to 20% between 1991-2000, and perhaps soon it will become a rarity. (16) The reported overall prevalence rates of polypharmacy in psychiatry vary between 13%-90% with a continuing debate about its merits and demerits. (17-18) A study from NIMH shows that prescription of 3 or more medications at discharge increased from 5% in 1974 to 40% in 1995. (19) Even evaluation of baseline medication data of schizophrenia patients in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial revealed that schizophrenia patients were being given polypharmacotherapy. Around 6% patients were taking two antipsychotics, 38% antidepressants; 22% anxiolytics; 4% lithium; and 15% other mood stabilizers. (20)

Psychiatric polypharmacy is not only widespread in adult population, but it is also increasingly been seen in child and adolescent population. In a nationally representative sample of 3,466 children and adolescents, the prevalence of multi-class psychotropic treatment was 19% in this population. Antidepressants were the most common co-prescribed medication class in multi-class visits followed by ADHD medications, antipsychotics, mood stabilizers, and sedative-hypnotics. (21) Multi-Class Polypharmacy is the most prevalent type of polypharmacy found in 20.9% of patients. In Multi-Class Polypharmacy, the combination of antidepressants with a benzodiazepine is the most common, and in some of these cases several benzodiazepines have been prescribed at the same time to the same patients. (22-23)

 

Conclusion:

While the common sense, logical and proper medical practice dictates the use of medication when needed and the least the better, polypharmacy or prescribing more than one medication, and often more than a few seems to be the common rule of practice than the exception. In many such cases the helplessness of both patients and physicians as prescribers to treat a non-responsive medical condition is the trigger behind polypharmacy. Also in many of these situations, symptomatic treatment and not the causal treatment are the reasons behind such non-scientific and unethical mode of practice. Attempts for prevention of medical complications, such as the prescription of anti-thrombotic agents in a hypertensive or coronary artery disease patient before occurrence is another common reason of polypharmacy practice.

In many symptomatic treatment cases such as the pain management, the pathologic cause or locus of pain is not treated but the reception of the pain by the brain is blocked by narcotic analgesics even methadone and nowadays medical marijuana, and in some cases opium. In psychiatry where polypharmacy ranks the second after cardiovascular diseases in the elderly population, but ranks number one in the adult population, symptomatic treatment with benzodiazepines and multi-class or even single-class polypharmacy, for example the use of more than one antidepressants or antipsychotics is beyond the scientific comprehension.

 

To control polypharmacy, both the prescribers and the patients need to be educated and aware of the detrimental effects of poypharmacy that may spoil the good initial intention. Both sides need to be aware of the availability of non-pharmacological methods of management and prevention of many medical conditions, such as exercise, diet and healthy life styles and removal of insults and pathogens such as smoking, drugs and alcohol from one’s life. Moreover the physicians need not to be too dependent on the treatment guidelines that suggesting and encouraging polypharmacy, while such proscribing medical agencies need to be aware of promoting polypharmacy, hence more morbidities and mortalities instead of optimal management. The society at large including the politicians and policy makers, along with the medical field and the patient subjects need not to undermine the long-haul detrimental impact of the narcotic use in different formats such as management of pains, sleep and as tranquilizers or for their numbing effects. In addition to known effect of addiction and dependency, these agents are the main cause of cognitive, memory and learning impairments and cause of early dementias. Lastly people need to be aware of the over-usage of OTC (over-the-counter) medications or natural products as they are known or commercialized, that they are still medicines and have chemical structures with chemical properties that interact with prescribed medicines, and alone or in combination could cause more harms than benefits.   

 Reference:

  1. Colley CA, Lucas LM. Polypharmacy: the cure becomes the disease.J Gen Intern Med. 1993 May; 8(5):278-83.
  1. Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients.Am J Geriatr Pharmacother. 2007 Dec; 5(4):345-51.
  1. Gorard DA. Escalating polypharmacy. QJM. 2006 Nov; 99(11):797-800.
  2. Bjerrum L, Rosholm JU, Hallas J, Kragstrup J. Methods for estimating the occurrence of polypharmacy by means of a prescription database.Eur J Clin Pharmacol. 1997; 53(1):7-11.
  1. Mjörndal T, Boman MD, Hägg S, Bäckström M, Wiholm BE, Wahlin A, Dahlqvist R. Adverse drug reactions as a cause for admissions to a department of internal medicine. Pharmacoepidemiol Drug Saf. 2002 Jan-Feb; 11(1):65-72.
  2. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002 Jan 16; 287(3):337-44.
  3. Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish Prescribed Drug Register.Drug Saf. 2007; 30(10):911-8.
  1. Hovstadius B, Astrand B, Petersson G. Dispensed drugs and multiple medications in the Swedish population: an individual-based register study. BMC Clin Pharmacol. 2009 May 27; 9():11.
  1. Hovstadius B, Hovstadius K, Åstrand B, Petersson G. Increasing polypharmacy – an individual-based study of the Swedish population 2005-2008. BMC Clinical Pharmacology. 2010;10:16.
  2. Moen J, Norrgård S, Antonov K, Nilsson JL, Ring L. GPs’ perceptions of multiple-medicine use in older patients. J Eval Clin Pract. 2010 Feb; 16(1):69-75.
  3. Walckiers D, Van der Heyden J, Tafforeau J. Factors associated with excessive polypharmacy in older people. Archives of Public Health. 2015;73:50.
  4. Campbell CI, Weisner C, Leresche L, Ray GT, Saunders K, Sullivan MD, Banta-Green CJ, Merrill JO, Silverberg MJ, Boudreau D, Satre DD, Von Korff M. Age and gender trends in long-term opioid analgesic use for noncancer pain. Am J Public Health. 2010 Dec; 100(12):2541-7.
  5. Soelberg CD, Brown RE Jr, Du Vivier D, Meyer JE, Ramachandran BK. The US Opioid Crisis: Current Federal and State Legal Issues. Anesth Analg. 2017 Nov;125(5):1675-1681.
  1. Ghaemi SN. Polypharmacy in psychiatry. New York: Marcel Dekker; 2002.
  2. Mojtabai R, Olfson M. National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch Gen Psychiatry. 2010 Jan; 67(1):26-36.
  3. Rittmannsberger H. The use of drug monotherapy in psychiatric inpatient treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr; 26(3):547-51.
  4. David T. Antipsychotic prescribing – time to review practice. Psychiatric Bulletin. 2002;26:401–2.
  5. Stahl SM. Antipsychotic polypharmacy: evidence based or eminence based? Acta Psychiatr Scand. 2002 Nov; 106(5):321-2.
  6. Presborn SH, Flockhart D. Guide to Psychiatric Drug Interactions. Primary Psychiatry. 2006;13:35–64.
  7. Chakos MH, Glick ID, Miller AL, Hamner MB, Miller DD, Patel JK, Tapp A, Keefe RS, Rosenheck RA. Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial. Psychiatr Serv. 2006 Aug; 57(8):1094-101.
  8. Comer JS, Olfson M, Mojtabai R. National trends in child and adolescent psychotropic polypharmacy in office-based practice, 1996-2007. J Am Acad Child Adolesc Psychiatry. 2010 Oct; 49(10):1001-10.
  9. De las Cuevas C, Sanz EJ. Polypharmacy in psychiatric practice in the Canary Islands. BMC Psychiatry. 2004 Jul 5; 4():18.
  10. Kukreja S, Kalra G, Shah N, Shrivastava A. Polypharmacy In Psychiatry: A Review. Mens Sana Monographs. 2013;11(1):82-99.

 

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