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The Role of Rational Polypharmacy in Pain Management

Friday, November 11, 2011   (0 Comments)
Posted by: Joy Ingram
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Kevin L. Zacharoff, MD


Pain is a complex phenomenon, whether acute or chronic, neuropathic or nociceptive. Although sometimes acute pain of a very specific nature and source may seem to be one single "type” of pain, such as post-surgical pain, it is theorized that even then, the painful sensation may have multiple components.

The International Association for the Study of Pain (IASP) defines pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." This definition acknowledges that pain is not just purely the result of tissue damage, and is often not well correlated with the degree of tissue damage. The likelihood may be that pain is somewhat more of a syndrome than a symptom.

The fact that the painful experience may often be the result of a variety of etiological sources makes an integrated approach to pain management the best approach in many situations. It naturally follows then, that rational polypharmacy, which refers to the use of more than one medication to treat a medical condition, should be part of a modern, multidisciplinary approach to many medical conditions, including pain, especially when treating pain that is chronic in nature.

It is important to remember that although the term "rational polypharmacy" is often used interchangeably with "multimodal therapy,” they are two very different approaches, and may actually often be used together.

  • multimodal therapeutic approach to pain management refers to the use of a variety of different and integrated disciplines (pharmacologic and non-pharmacologic) to control pain; for example, using medications and physical therapy together. Very often in a multimodal approach there may be several integrated disciplines. The logic of this combination of modalities is rational, and the intended goal is to control pain from a variety of different approaches, which in some cases may be radically different.
  • The concept of using polypharmacy in a rational way sometimes referred to as combination pharmacotherapy, refers to integration of one or more pharmacologic agents through a systematic selection that has the most synergistic effect to manage a painful condition. Additionally, while striving to achieve the goal of pain control, it is desirable to maximize benefit of treatment while minimizing risk and negative or adverse effects of those treatments. In certain patients, the rationale may be to use agents of differing onset of action or duration of action to maximize pain relief, as well as to minimize episodes of breakthrough pain.

There are a number of different pharmacologic agents that are often used alone or in a variety of combinations to combat pain.

Examples of these medications include:

Non- opioids


Non-steroidal Anti-inflammatories (NSAIDS)













Adjuvant Analgesics

Tricyclic Antidepressants





Local anesthetics (lidocaine)


Additionally, along with these medications, there may be other medications introduced on an interventional basis by injection. In some cases the success of these interventional treatments is facilitated by concurrent administration of systemic medication, once again capitalizing on the polypharmaceutical approach.

In most cases of chronic pain treatment, striving toward the balance between pain reduction and adverse effects is omnipresent. It may seem most convenient to use a monotherapeutic pharmacologic approach that doesn’t require attention to be paid to competing mechanisms of metabolism, drug-drug interactions, etc. But this one-medication approach is often met with escalation of doses of medication needed for adequate pain control. When a plateau of dosing is reached, the solution is often drug discontinuance and switching, while a multi-drug approach may have been more effective and efficient.

The design of a polypharmaceutical regimen is based on a number of factors, and requires thoughtful consideration. In many cases, the logic is fairly simple. If the thinking is that there is an inflammatory component to the patient’s chronic pain, it seems reasonable to utilize an NSAID along with an opioid. In fact, the World Health Organization’s three-step ladder approach to treatment of cancer pain clearly illustrates the logic of this approach. In the same fashion, it may follow that use of adjuvant agents along with opioids or non-opioids may benefit the patient.

A number of published guidelines for treatment of different types of chronic pain illustrate the benefits of the polypharmaceutical approach.

When using medication combinations to treat pain, it is best to rely on validated applications to the degree possible, as unexpected results may surface, and specific recommendations for management are often in published studies that can be invaluable. When data is not available, it is important to lay out a strategy based on physiologic and sound judgment that has clear-cut goals in mind, with the intention that if these goals are not reached, modifications in the regimen can be made.

Keep in mind that patients may have seen multiple clinicians in the course of seeking treatment for chronic pain. It is important to avoid unintentional polypharmaceutical treatment, as there is the likelihood that patients may have accumulated a store of many medications. Obviously, educating patients about the risks of self-combining medications, and avoidance of that practice, is a critical piece of patient education and safe management. Rational polypharmacy is safe and practical only when guided by the healthcare provider.


1. Kingsbury SJ, Yi D, Simpson GM. Psychopharmacology: rational and irrational polypharmacy. Psychiatry Serv. 2001; 52(8):1033-6

2. Gallagher RM. Am J Phys Med Rehabil. 2005 Mar; 84(3 Suppl):S64-76. Rational integration of pharmacologic, behavioral, and rehabilitation strategies in the treatment of chronic pain

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