Polypharmacy: Some Art, Some Science-Much Alchemy

July 28, 2011

Polypharmacy has become so ubiquitous that more accidental overdoses are now caused by prescription drugs than by street drugs. The question naturally arises whether this almost routine use of multiple psychotropic medications make sense?

Polypharmacy has become so ubiquitous that more accidental overdoses are now caused by prescription drugs than by street drugs. The question naturally arises whether this almost routine use of multiple psychotropic medications make sense? The answer is mixed -- sometimes,yes; often maybe; and far too frequently, no. Polypharmacy is sometimes absolutely indicated as a standard of practice; sometimes it is a last resort clinical art necessary for otherwise intractable problems; sometimes it is a sign of poor prescribing and magical thinking akin to alchemy.

The best indications for polypharmacy are few and well established:
1. Bipolar depression
2. Psychotic or agitated depression
3. Co-morbid conditions that require independent medications (eg, ADD and major depression)
4. When partial response to the first medication requires adding another adjunctively
5. When there is a combination of psychiatric and pain problems

There is a middle ground where polypharmacy is desirable (maybe even necessary), but has to be practiced as an art form without any clear guidelines that are based on research. This is because research on polypharmacy is so very inconvenient and expensive, requiring a large number of cells and a huge sample size. Artistic polypharmacy is most required and successful when a patient with an especially difficult or nonresponsive problem meets a clinician with special skills in custom tailoring a multiple drug regimen to produce a felicitous combination of optimal efficacy and minimal side effects.

Unfortunately though, a great deal of polypharmacy lacks any apparent rhyme, reason, or rational. Several traps lead to such alchemical polypharmacy:  

o Drugs that haven't worked at all are continued indefinitely, even as new drugs are added
o Drugs are given to chase the side effects of the other drugs the patient is taking
o Medications are prescribed for each individual symptom the patient presents with
o Some practitioners have their favorite (often changing) combinations that they give to almost every patient
o The patient is receiving uncoordinated treatments dispensed by different doctors (particularly a problem for those receiving pain or sleep medicine independently prescribed by their primary care physician
o Some patients seek out multiple medications (particularly a problem for the prescription pain and attention deficit drugs) 
 
Recently the US army reported an alarming increase in overdose deaths in patients receiving high doses of multiple, interacting medications. Polypharmacy has been a problem for 30 years, but seems to be even more common and dangerous now than ever before because of:  

o The heavy use of prescription pain drugs that are synergistically sedative with psychotropic medication
o The aggressive marketing of drug companies promoting overuse of their products
o A reduction in psychotherapy resources
o The tendency to treat individual symptoms-- not syndromes
o The failure to give monotherapy a fair chance because of inadequate dose and duration
o Polypharmacy has become an unchallenged style of practice
o Patients are more drug-seeking because of advertising and the seductiveness of pain drugs
o A failure to accept that some patients simply don't respond well to any medication, and that piling on more drugs may often cause more harm than good

The problems caused by polypharmacy are clear; their solution much less so. Clinical research is unlikely to march to the rescue-- the studies are just too hard to do. The best makeshift is first rate quality control using target indicators that are built into the patient's electronic record. All patients on polypharmacy should be tagged and monitored at frequent and regular intervals to ensure that there is an appropriate clinical rationale for each drug and a review of its efficacy, side effects, and possible drug/drug interactions.  

A cautionary note: to patients currently taking many medications and concerned about whether this is a good idea. First: don't change anything on your own. You may need all the medications you are on and/or may have withdrawal problems if you stop suddenly. Ask your doctor to review the medications with you, discuss their current role, and make plans for possible future adjustments. A second opinion may be helpful if you are not getting better, or have lots of side effects, or continue not to understand the rationale for all the medications you are taking. Polypharmacy may be just right for you, but it is always good to be informed about it and to ensure it makes sense.