Polypharmacy Subtypes the Necessary, the Reasonable, the Ridiculous, and the Hazardous

By Nasrallah, Henry A. | Current Psychiatry, April 2011 | Go to article overview

Polypharmacy Subtypes the Necessary, the Reasonable, the Ridiculous, and the Hazardous


Nasrallah, Henry A., Current Psychiatry


You've heard about the 2 certainties in life: death and taxes. In psychiatric practice with complex and chronic patients, there is a third certainty: polypharmacy. It ranges from thoughtful to indiscriminate and seems to be entrenched in clinical practice, possibly reflecting practitioners' desperation in trying to manage severely ill, treatment-resistant patients, usually in the absence of evidence-based guidelines.

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I never fail to encounter polypharmacy in hospitals or clinics where I consult. I always wondered how the patient's doctor knew which drug was exerting a therapeutic effect or which drug was causing side effects (parkinsonism, akathisia, sedation, orthostasis, dizziness, headache, blurry vision, etc.). Over time, I came to categorize polypharmacy into 4 subtypes that span the spectrum from sensible to absurd. Here is my personal classification, which I trust that you, my readers, have witnessed as well.

Necessary polypharmacy. This variant of polypharmacy is evidence-based and proven in double-blind studies to be more effective than monotherapy. The most prominent example is adding an atypical antipsychotic to a mood stabilizer in bipolar mania. In fact, the superior efficacy of combination therapy in bipolar disorder is one of the oldest forms of rational polypharmacy, is supported by FDA trials, and is indicated whenever mood stabilizer monotherapy is not sufficient. For example, combining lithium and valproate is superior to either drug alone. Another example of FDA-approved combinations is combining small doses of an atypical antipsychotic to an antidepressant for treatment-resistant depression.

Reasonable polypharmacy. Although many of the combinations in this category are not FDA-approved, controlled studies support their use for suffering patients. Examples include:

* An atypical antipsychotic added to a selective serotonin reuptake inhibitor (SSR1) for obsessive-compulsive disorder (OCD) patients who do not improve on SSRI monotherapy.

* Modafinil added to clozapine in patients who suffer substantial and persistent daytime sedation or somnolence.

* Combining 2 antidepressants for major depressive disorder patients who partially respond to 1 antidepressant.

* Combining a mood stabilizer with an antidepressant for bipolar depression to prevent mood switching.

Ridiculous polypharmacy. The sky is the limit to the variations and degrees of ridiculous polypharmacy, but the theme is the same: an absurd concoction of psychotropic drugs across several classes, often including multiple agents from 1 or several classes. …

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