21. Polypharmacy

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© Springer Nature Switzerland AG 2020
O. FreudenreichPsychotic DisordersCurrent Clinical Psychiatryhttps://doi.org/10.1007/978-3-030-29450-2_21



21. Polypharmacy



Oliver Freudenreich1 


(1)
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

 


Keywords

PolypharmacyRational prescribingDeprescribingPreventionHippocratic medicineBeer Criteria®



Essential Concepts






  • Polypharmacy is a fuzzy concept since, at the molecular level, antipsychotic monotherapy constitutes intrinsic polypharmacy.



  • Appropriate reasons for combination treatments are as follows: added efficacy for the primary symptom cluster, supplemental symptom control for comorbid symptoms, and adjunctive to increase tolerability.



  • Fixing unnecessary polypharmacy (deprescribing) requires patience and persistence and can run counter to patient expectations. Knowing how to stop a medication is as important as knowing how to start it.



  • Time-limited trials and measuring outcomes are safeguards against polypharmacy. A small improvement in a symptom might be neither clinically meaningful nor justification for the long-term risk of the medication.



  • Polypharmacy can flag treatment refractoriness.



  • The acute treatment requires more and/or different medications than the maintenance phase (cf. oncology and cancer treatment).



  • Hippocratic medicine demands that you treat diseases (and not simply symptoms) and that your intervention is effective (and not simply safe). Sometimes this would suggest doing nothing, one of the most difficult things to do in medicine.




“Simplify, simplify.” [1]


–Henry David Thoreau, American transcendentalist, 1817–1862


Today, treatment with more than one medication is the norm, not the exception, for almost any disorder (e.g., hypertension, diabetes), including psychiatric disorders (e.g., bipolar disorder). Unless you have a framework that guides your prescribing practice, patients are at risk for unnecessary and harmful polypharmacy (and you are at risk of being quickly relegated to merely dispensing medications as the patient’s psychopharmacologist [2]). In 2006, up to one third of psychiatric outpatients received three or more psychiatric medications [3]. A decade earlier, this percentage was only 17%. I would argue that this increase represents overtreatment today rather than undertreatment 10 years ago. Overtreatment is clearly a challenge that is now recognized by medical societies. The Choosing Wisely campaign represents one visible effort at the level of professional organizations to reduce unnecessary tests and wasteful prescribing [4], in recognition of a shared professional responsibility to limit risks to patients and to be stewards of scarce resources. The American Psychiatric Association has signed on to this effort; one recommendation relates to polypharmacy and states: “don’t routinely prescribe two or more antipsychotics concurrently” [5]. You may want to sign on yourself, asking the Kantian question: would my way of prescribing lead to good, socially acceptable outcomes if followed by all physicians treating similar patients?



Key Point


You must treat schizophrenia spectrum disorders as the syndromes that they are: for most patients, chronic illnesses for which you try to prevent relapse and improve function along the way. With this longitudinal (and overarching) view, any prescribing that is merely symptom-based and cross-sectional will lead to polypharmacy since there is invariably another symptom to target. Sometimes, the most difficult thing to do in medicine is to do nothing.


We have no agreed-upon definition of what constitutes “polypharmacy.” In its narrowest sense, polypharmacy refers to the combination of two or more antipsychotics (same-class polypharmacy). In a slightly broader sense, polypharmacy refers to using two or more medications for the same condition. In its broadest sense, it is simple pill counting. Polypharmacy often has a negative connotation and implies the use of (too) many or unnecessary medications. What is rarely talked about is that at the molecular level, the concept might not be very meaningful at all [6]. Monotherapy with clozapine at the pill-counting level is polypharmacy at the molecular level – clozapine targets a multitude of receptors in the brain. With such a fuzzy concept, it is easy to see how one person’s rational combination treatment becomes another person’s irrational polypharmacy. Still “polypharmacy” has some face validity as a shorthand description for a medication regimen that seems overly complex and that therefore warrants review.


“Just doing something” is a poor long-term strategy, particularly in the management of a lifelong disease with no spontaneous remission. Not every complaint should make you reach for the prescription pad. Apart from cost, clear risks from polypharmacy are the potential for drug interactions, broadening side effects or even limiting effectiveness if medication effects cancel each other out (Table 21.1). The more medications a patient is prescribed, the more opportunities there are for making mistakes taking them or administering them. Psychologically, it can prevent the hard work of acceptance if one focuses on the elusive goal of a cure and result in a dependent patient who relies solely on pills, a iatrogenic loss of self-efficacy. Last, even a “safe” medicine can have an idiosyncratic, catastrophic side effect for your patient – a point often overlooked by staff members who pressure you to do something (i.e., prescribe a medicine) for a challenging patient.


Table 21.1

Risks of antipsychotic combination treatment


















Loss of “atypicality” of antipsychotics (if a first-generation antipsychotic is added to a second-generation antipsychotic)


Added toxicities (short and long term)


Expense


Drug-drug interactions (leading to antipsychotic drug level changes)


Loss of efficacy (if the added medication counteracts the mechanism of action)


Opportunity cost (non-medication solutions are not explored)


Appropriate Use of Polypharmacy


In medicine, “rational” polypharmacy is evidence of a good understanding of pathophysiology. Today, diabetes or hypertension is often treated with medication combinations that target different enzymes in the metabolic pathways or different receptors, acting synergistically. In schizophrenia, it is paradoxically the lack of knowledge of pathophysiology that justifies the empirical use of multiple medications. Polypharmacy is also logical for a complex disease like schizophrenia if you accept that antipsychotics are not “antischizophrenics”: it makes sense to use other drug classes to target symptom clusters not ameliorated by antipsychotics (e.g., depression – see Chap. 19).


These are then three reasonable clinical scenarios (and one more controversial) in which you would use more than one psychotropic:



  • For added efficacy – If there is treatment resistance and you need to augment a partial response of core symptoms to your primary treatment.



  • For supplemental symptom control – If you need to target specific symptoms, for example, insomnia or agitation not covered by your primary treatment.



  • For treatment intolerance – If adjunctive medications are needed to improve tolerability of your primary treatment.



  • For psychological support – Engagement of patients with medications in a supportive mode can require the prescribing of medications with marginal or no benefit. This cannot be your principle mode of operation, and it is only justified if done safely and judiciously.


Treating patients who are only partially responsive to antipsychotics remains more an art than a science, and frequently a second antipsychotic is added despite a paucity of data [7]. Risperidone augmentation of clozapine-treated patients is one example of an antipsychotic-antipsychotic combination that became prominent based on uncontrolled trials. Theoretically, adding dopamine blockade might be useful for some patients who need more dopamine blockade than the fairly loosely bound clozapine provides. Subsequent double-blind trials and meta-analyses have not conclusively resolved the question of added efficacy for this particular combination (or any other combination), leaving the clinician with the need to decide on a case-by-case basis [8, 9].


If you decide you must add a second antipsychotic (even though all schizophrenia guidelines recommend antipsychotic monotherapy), propose a time-limited trial, measure psychopathology, and judge if any change in psychopathology is clinically useful. If the change is not obvious to other people, it probably does not justify the added risks. Which psychotropics to combine is discussed in more detail in the chapters on ancillary medications (Chap. 19), on refractory psychosis (Chap. 12), and on clozapine (Chap. 17).



Tip


Polypharmacy can be a sign of true (i.e., biological) poor treatment response. Make sure you are using the most effective medication for a given diagnosis, including clozapine for refractory schizophrenia; only augment clozapine, not other antipsychotics.


Diagnosing Questionable Polypharmacy


In order to judge a regimen with regard to its appropriateness, ask yourself four questions: What kind of disease are you dealing with? What kind of patient has the disease? What kind of physician is trying to manage the patient and his disease? What kind of society are you practicing in? Answering these questions will help you identify the four main etiological factors (the disease, the patient, the physician, the healthcare system or society) that contribute to polypharmacy [10] (Table 21.2).
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Aug 14, 2021 | Posted by in PSYCHIATRY | Comments Off on 21. Polypharmacy

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