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Psychiatric Polypharmacy: The Good, the Bad, and the Ugly

Psychiatric Polypharmacy: The Good, the Bad, and the Ugly

A great deal of data exists about the dangers of polypharmacy. Persons with psychiatric disorders experience increased risk for adverse drug interactions because of the great frequency with which multiple medications are used.1 Using multiple antipsychotics concomitantly has been associated with increased mortality in patients with schizophrenia.2 Reports of adverse psychiatric polypharmacy effects are abundant, including increased duration of hospital stay.3

In this article we define polypharmacy as the use of 2 or more medications of the same chemical class or with the same or similar pharmacological actions to treat the same condition or separate conditions. For example, prescribing thyroid medication to augment antidepressant response would be polypharmacy, while using thyroid medication to treat hypothyroidism, with concomitant antidepressant therapy for depression would not be considered polypharmacy (Table 1).

General examples of polypharmacy
  Aripiprazole + haloperidol for psychosis  
  Valproic acid + lamotrigine for mood stabilization  
  Same chemical class to treat separate conditions  
  Clonazepam for anxiety + temazepam for sleep  
  Risperidone for psychosis + low-dose quetiapine for anxiety  
  Same pharmacological action to treat the same condition  
  Diphenhydramine + temazepam for sleep  
  SSRI + nortriptyline for depression  
  Same pharmacological action to treat separate conditions  
  SSRI for depression + bupropion for smoking cessation  
  SSRI for depression + low-dose trazodone for sleep  
  Similar pharmacological action to treat the same condition  
  Temazepam + zolpidem for sleep  
  Antidepressant + triiodothyronine or thyroxine for depression  
  Similar pharmacological action to treat separate conditions  
  Venlafaxine for depression + low-dose amitriptyline for pain  
  Mirtazepine for depression + ondansetron for nausea  

Although the use of multiple medications to treat different conditions is beyond the scope of this paper, it should be realized that there is a potential for problems any time multiple medications are used. As an example, cases of carbamazepine toxicity have been reported when this mood stabilizer is used in combination with protease inhibitors for HIV because of the well-known CYP3A4 inhibition of this antiretro- viral class.4

A medication that treats the adverse effects of another agent would not be considered polypharmacy by this definition. For instance, using anticholinergic agents to treat extrapyramidal side effects of first-generation antipsychotics or the use of amiloride to treat lithium-induced polyuria may be empirically based. However, the need for 2 medications might be avoided with the use of second-generation antipsychotics in the first example or valproic acid in the second example.

The term polypharmacy does not in itself suggest whether its use is warranted. Ideally, only one medication would be used to optimally treat a symptom or disorder. However, even a cursory review of the literature suggests that many, if not most, patients show suboptimal response to any one given agent. New medications more specifically target disease state symptoms and have improved side-effect profiles, making combination treatment strategies more attractive and possibly less daunting. The legitimate increase in pressures to help improve patient status has changed the standard for successful treatment in psychiatry; the bar has been raised.

Perhaps the best example of this phenomenon is in the treatment of depression. Response is no longer considered an acceptable goal—remission is now the clear end point for therapy. Multiple lines of evidence show that patients who only respond have a poorer quality of life and are more likely to relapse.5,6

There are certainly some well-researched uses of medication combinations. Even casual reflection shows that the number of possible medication combinations to treat any psychiatric condition is enormous. Surveys have found that the use of 4 or 5 medications simultaneously is not uncommon in the treatment of bipolar disorder7 or other psychiatric conditions.8,9 Given the overwhelming number of possible combinations, it is unlikely that more than a few of these will be researched.


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