Thomas AM Kramer, MD


Medscape General Medicine. 2000;2(3) 


Polypharmacy, or the use of multiple medications to treat a patient, has had some negative connotations. It has been perceived, at least, as less than elegant, and at worst, as extremely problematic to use anything more than the bare minimum of medications to relieve symptoms. In addition to the relative lack of aesthetic in putting multiple variables into the equation, there are some real problems that need to be considered.

No medication regimen has any hope of being effective if the medications themselves are not actually ingested. It is not sufficient that a certain combination of medications is effective. It is just as important that it is possible for the patient to take the medications as prescribed. Combinations that are so complicated that the patient cannot keep track of them will not treat patients' symptoms regardless of how wonderful the medications may work individually or together. Patients, for the most part, have a complicated psychological relationship with their medications. If patients feel intellectually defeated by the medications that have been prescribed -- that is, if they do not feel smart enough to manage the medications as prescribed, then they will disengage from treatment and not take some or all of their medication.

In this day and age where medical decision making is often influenced and sometimes determined by financial considerations, it is common for practitioners to become frustrated and often resentful when cost becomes an issue in determining the appropriate treatment for a patient. The most common scenario for such a reaction is when a physician is told that there is an alternative treatment that is almost as good and considerably less expensive. When the third parties interject themselves into the doctor-patient relationship in this way, it is easy for a physician to feel that the fiscal constraints and not quality of care are leading American medicine in the 21st century. In spite of all this, however, cost must be considered as an issue for determining the treatment plan. Once again, if the cost of a particular combination of medications makes it impossible for patients to get the medications, they will not take them, and as such the medication regimen will be ineffective. Even the most generous insurance plans have limitations or copays on medications. It is important when considering polypharmacy to consider the financial impact at least on the patient, if not on the healthcare system as a whole. The more medications prescribed, the higher the cost, and the more complications are created as a result.

As psychopharmacology has developed through the last few years, with new agents and new combinations of agents, the issue of drug interactions has come to the forefront of our daily practice. Many psychiatrists often wish they could go back to their medical school pharmacology course and perhaps this time, pay a little more attention, particularly to the issues of enzyme induction and inhibition. Pharmaceutical companies in their promotional materials often stress certain aspects of their medication's pharmacokinetics to make their medication look particularly better, safer, or easier to use. Practitioners need an enormous and ever increasing knowledge base, not only to know the interactions of the medications that they prescribe, but also to know which statements made by pharmaceutical representatives are real or exaggerations. To state the obvious, when it comes to polypharmacy, the more medications that are prescribed, the more opportunities there are for drug interactions. This is particularly an issue for nonpsychiatric medications, and the complications derived from multiple physicians prescribing for the same patient. While we may feel that we are on top of the interactions between the medications that we are prescribing ourselves, things can often get complicated and sometimes dangerous when there are multiple practitioners in the patient's medical system.

Another issue often cited in discussions about polypharmacy is the problems created by side effects in these regimens. In an ideal world, we would start each medication 1 at a time, determine the side effects of each medication as it is initiated, and then be able to say with some certainty what side effects were caused by which medication. Unfortunately, in the real world, often acutely ill patients and time constraints preclude being able to leisurely begin polypharmacy. Too often, we start more than 1 medication at once and then we are left with the task of trying to figure out how to deal with side effects that may come from multiple medications or multiple combinations of medications. The complex diagnosis and management of side effects from multiple medications present 2 different sets of problems: short-term and long-term side effects.

Short-term side effects, such as the sedation that occurs from treating a patient with 2 different sedating medications, are often transient but can make the initial phase of a medication regimen enormously difficult for the patient to tolerate. Two medications with very mild sedative effects often create formidable sedation when used together. Long-term side effects occur for similar reasons. Mild weight gain caused by 2 different medications can become severe weight gain when the medications are given together. When putting together a particular cocktail of medications, one must consider both short- and long-term issues of the additive effects of medications.

Einstein once said, "Make things as simple as possible. Never simpler." This is as good advice for psychopharmacology as it is for anything else. Often, in our quest for simplicity for the reasons mentioned above, we will use monotherapy or limit the number of agents in a quest to make things simpler than they really are. Multiple medications are not only often necessary, they are often desirable. First of all, the efficacy of our medications is not always sufficient for monotherapy to treat the patient in any comprehensive or definitive way. For example, for most antidepressant trials, drug efficacy is established by a reduction of 50% in whichever depression scale is used in the study. That certainly shows a drug effect, but no clinician would be happy with simply a 50% reduction in symptoms. Sometimes it takes more than 1 pharmacologic agent to alleviate symptoms to a satisfactory extent. In addition, some symptoms present early in the illness but resolve after treatment. If the monotherapy treats them all, it could later end up having too many effects. For example, for both bipolar and unipolar patients, insomnia is common. However, once these disorders are treated with mood stabilizers or antidepressants, the insomnia disappears relatively quickly and the patient might begin to feel sedated from the ongoing treatment for the symptom.

Although compliance can often be a problem with multiple medications as described above, there is a simple way to maximize compliance with a multiple medication regimen. Patients struggle with multiple doses, not multiple medications. It is relatively easy to keep track of a bunch of different pills if you can take them all at the same time. If you need to take different medications at different times, then the complexity of the regimen becomes prohibitive. It is important for the psychopharmacologist to make sure that the patient's schedule and routine are relatively easy to understand and follow, and that means limiting the number of doses much more than it means limiting the number of medications.

Similarly, the issue of drug interactions can also be dealt with to make polypharmacy both safe and effective. For the most part, it is simply a matter of paying attention. Assume, until proven otherwise, that every medication combination is problematic. As a result, all polypharmacy must be researched to establish its safety. This is less difficult than it sounds. Most of the polypharmacy used in the community consists of well-established combinations of medications. For example, combining antidepressants such as an SSRI and bupropion or mood stabilizers such as valproate and lithium are not only established as effective but safe. Just because combinations of drugs can interact does not mean that they will and, in fact, most of the time they do not. The crucial issue is to make sure that your patient is telling you all of the medications he or she is taking, not just the ones that are prescribed by you or even just the ones that are prescribed, because many patients are taking over-the-counter and health food store preparations. If attention is paid to these factors, drug interactions are an easily managed issue.

It is the nature of most, if not all, behavioral illnesses that symptoms change over time. As symptoms change, medication needs change. Pharmacotherapy with a single agent for a behavioral illness sometimes proves to be inadequate, and sometimes proves to be too much, as in the case of the medication that may be treating symptoms, such as insomnia or lethargy, that are no longer present. The effects of the medication remain as long as the medication remains. What was once a therapeutic effect is now the antithetical side effect. The use of polypharmacy may prove to be ultimately better for a given patient because it is so much more flexible in that it is more easily adapted to changes that the patient may experience over time.

Finally, psychiatrists in the practice of psychopharmacology who avoid polypharmacy may be doing themselves and our profession a disservice. It is little commented about but often noticed that nonpsychiatric physicians are treating most of the patients diagnosed with depression in the community. The reason for this is that it is simple to treat depression; all a primary care physician has to do is to give them one of the many excellent first-line antidepressants, usually an SSRI, and most of the time that will be sufficient to alleviate most of the patient's symptoms. In short, you do not need a psychiatrist anymore to treat depression. It is only the most treatment-refractory cases -- usually the ones that require polypharmacy -- that come to our attention. To a great extent it is severe psychopathology and polypharmacy that are left to psychiatry in the current healthcare system. If a pharmaceutical company developed medications for schizophrenia or severe bipolar disease that would treat all of the symptoms all of the time with very few side effects, psychiatry would be threatened with irrelevance. Thus, polypharmacy is more than something that may be helpful to patients. It is one of the tools that we have to offer. It is crucial for us to take it seriously.