Journal of Psychosocial Nursing and Mental Health Services

Psychopharmacology 

Off-Label Prescribing and Polypharmacy: Minimizing the Risks

Laura G. Leahy, DrNP, APRN, PMH-CNS/FNP, BC

Abstract

Off-label prescribing and polypharmacy are commonplace in today's health care environment. Patients are treated with multiple medications obtained through multiple providers, and all too frequently, there is no collaboration amongst professionals. Nurses can address these issues by educating themselves and their patients regarding medication indications and uses, side effects, risks, and benefits. By exploring a patient's medication reconciliation, including over-the-counter agents, and identifying the U.S. Food and Drug Administration–approved indications, as well as potential off-label uses and overlapping side effects of the medications prescribed, nurses can facilitate collaboration among prescribers to reduce polypharmacy, minimize medication side effects, and alleviate drug–drug interactions, while improving patient outcomes and quality of life. [Journal of Psychosocial Nursing and Mental Health Services, 55(2), 17–22.]

Abstract

Off-label prescribing and polypharmacy are commonplace in today's health care environment. Patients are treated with multiple medications obtained through multiple providers, and all too frequently, there is no collaboration amongst professionals. Nurses can address these issues by educating themselves and their patients regarding medication indications and uses, side effects, risks, and benefits. By exploring a patient's medication reconciliation, including over-the-counter agents, and identifying the U.S. Food and Drug Administration–approved indications, as well as potential off-label uses and overlapping side effects of the medications prescribed, nurses can facilitate collaboration among prescribers to reduce polypharmacy, minimize medication side effects, and alleviate drug–drug interactions, while improving patient outcomes and quality of life. [Journal of Psychosocial Nursing and Mental Health Services, 55(2), 17–22.]

Exploring psychotherapeutic issues and agents in clinical practice

Patients diagnosed with psychiatric disorders often have medical and additional psychiatric comorbidities for which prescription drugs or over-the-counter (OTC) agents are prescribed. According to Moore and Mattison (2016), one in every six American adults reported taking prescription psychiatric medications on at least one occasion in 2013. Most psychotropic prescriptions were filled by White individuals, women, and older adults as well as long-term users (i.e., individuals taking the medications since 2011 or earlier) (Moore & Mattison, 2016). Although the U.S. Food and Drug Administration (FDA) offers approval for specific drug indications, many practitioners prescribe medications for symptoms or conditions that are not FDA approved. This practice is called “off-label” prescribing.

Many medications, including psychotropic agents, are used off-label to treat symptoms and conditions other than the FDA's approved labeling. For example, the prescribing of trazodone for insomnia, topiramate to combat weight gain due to psychotropic agents, or propranolol for anxiety would all be considered off-label uses of these medications. Another area of concern for patients, prescribing clinicians, and the health care industry in general is the growing use of polypharmacy. For purposes of this article, polypharmacy is defined as the prescribing or taking of multiple prescription and/or OTC medications, vitamins, or supplements over the course of a disease state, in combination with one another for multiple conditions and/or multiple drugs being taken at the same time. When patients present with comorbid medical and psychiatric illnesses, for which pharmacotherapy is indicated, the risk of adverse reactions, side effects, and drug–drug interactions increases with each agent prescribed or taken.

Case Example

A middle-aged man diagnosed with comorbid anxiety, hypertension, and insomnia develops cough and cold symptoms. He is prescribed a diuretic, an antihypertensive agent, and a non-benzodiazepine sleep medication through his primary care practitioner (PCP). He is also prescribed a selective serotonin reuptake inhibitor (SSRI) antidepressant agent FDA-approved for anxiety and a benzodiazepine agent through his psychiatric nurse practitioner (NP). The patient begins taking OTC cough and cold relief medication, containing acetaminophen, dextromethorphan, diphenhydramine, and phenylephrine. The addition of the cold medication has increased the patient's anxiety and blood pressure to the extent that he believes he is having a heart attack and seeks treatment at the local hospital's emergency department. This is just one example of how practitioners and patients inadvertently perpetuate the practice of polypharmacy.

The Incidence of Polypharmacy

The prevalence of noninstitutionalized adults older than 20 taking five or more prescription medications is estimated to be approximately 15% in the United States (Kantor, Rehm, Haas, Chan, & Giovannucci, 2015). However, this figure does not account for individuals also taking OTC drugs, vitamins, or complementary and alternative supplements; thus, the percentage may be even higher. Each additional agent a patient takes increases the risks of side effects and drug–drug interactions. So how do we navigate these challenges of off-label prescribing and polypharmacy to provide our patients with the most appropriate course of pharmacological treatment while reducing not only the risk of adverse events but also the number of drugs prescribed? One suggestion may be to explore the off-label uses of common psychotropic medications to reduce the incidence of polypharmacy.

Off-Label Prescribing

Off-label prescribing of medications is a common and legal practice and does not imply that the medication is being used in an inappropriate manner. Medications for psychiatric disorders are frequently used for non-FDA–approved indications based on patients' medication and medical history, their presenting symptoms, and the clinician's experience. Patients with psychiatric illnesses are often prohibited from participating in clinical trials, making the disorders difficult to study and lessening the chance for a drug to obtain an FDA-approved indication (Alexander, Gallagher, Mascola, Moloney, & Stafford, 2011). In addition, psychiatric symptoms often mimic one another across disorders, leading practitioners to prescribe medications approved for one specific indication to patients with conditions that are not approved uses per the FDA (Alexander et al., 2011).

A 1-year prospective study of patients attending an outpatient psychiatric department found that approximately 80% of patients received at least one prescribed medication written for a non-FDA–approved indication and more than 43% received prescriptions for more than one off-label drug (Kharadi, Patel, Rana, & Patel, 2015). Similarly, in a multi-hospital study, Smithburger et al. (2015) estimated that 44% of prescribed medications were for off-label uses and found that, when prescribed alone, those medications did not pose a higher risk for adverse drug reactions than medications prescribed for the FDA-approved indication; however, each additional FDA-approved or off-label medication prescribed and added to the patient's treatment regimen proportionately increased the risk of adverse events.

Although it is important for health care providers to justify the prescribing of multiple medications for a given disease state or varied conditions, it is also imperative for the clinician engaging in the practice of off-label prescribing to justify the use of the medication for the patient's presenting symptoms or conditions. Although the prescribing practitioner must inform the patient of these practices, as well as the side effects, risks, and benefits of off-label and polypharmacy prescribing, the rationale for the agents prescribed must be clearly documented in the patient's chart. In addition, nurses must provide education to patients and their families regarding the disease states, treatment plan, and medications prescribed and answer any questions that may arise. To effectively accomplish these goals, clear documentation of symptoms, conditions, and prescribing rationales is essential and collaboration among health care professionals is critical.

FDA-Approved Indications and off-Label Uses of Psychotropic Medications

Although not fully comprehensive, the Table offers information regarding the most common FDA-approved indications and off-label uses for various medications prescribed for the treatment of psychiatric conditions. Although the majority of medications listed have been prescribed for off-label purposes for decades, there are few clinical studies of these uses and many of those clinical trials occurred more than 10 years ago.


U.S. FOOD and Drug Administration (FDA)–Approved Indications and off-Label Uses of Common Psychotropic Medications
U.S. FOOD and Drug Administration (FDA)–Approved Indications and off-Label Uses of Common Psychotropic Medications

Table:

U.S. FOOD and Drug Administration (FDA)–Approved Indications and off-Label Uses of Common Psychotropic Medications

Nurses' Roles in Minimizing Risk

One way in which nurses can assist in reducing the risks associated with polypharmacy is to identify medications that can be beneficial for multiple purposes. This may entail recommending a medication for its FDA-approved indication that also has side effects, which can be beneficial to the patient's symptom profile, has off-label use for comorbid conditions, or both. Using the previous case example, the nurse in the PCP's office notices the multiple medications being taken by the patient and understands that the side effects of the antihypertensive agent, non-benzodiazepine sleep aid, and benzodiazepine agent are similar and may contribute to over-sedation, fatigue, and potentially depression. The nurse is also aware that some antihypertensive agents can be used to treat anxiety symptoms. The nurse facilitates collaboration between the PCP and psychiatric NP to explore the possibility of reducing the number of medications the patient is currently prescribed and taking.

During the collaboration, the psychiatric NP inquires whether a change in the antihypertensive agent to propranolol would be beneficial to address the patient's elevated blood pressure, an FDA-approved indication, and his anxiety, an off-label use. If the change in antihypertensive agent is effective in managing the patient's blood pressure and anxiety, the plan would be to taper and discontinue the SSRI antidepressant and benzodiazepine agents. In addition, given the sedating side effects of both the sleep aid and benzodiazepine agent, the clinicians agree to discontinue the sleep aid and reduce the benzodiazepine agent to an as-needed basis with a plan to discontinue in the near future. With the nurse's observation and proactive recommendation for provider collaboration, this plan would effectively reduce the patient's polypharmacy from five to two medications, using a combination of FDA-approved indications, off-label uses, and the medications' side effects to accomplish this goal.

Finally, the nurse also cautions the patient on the use of OTC cough and cold preparations and suggests he ask the pharmacist for recommendations regarding medications indicated for patients with high blood pressure and without the addition of diphenhydramine, which is often added to these remedies for its multi-symptom relief and sedating side effects. This level of collaboration between nursing, prescribing practitioners, the pharmacist, and the patient ideally will reduce polypharmacy, avoid adverse drug reactions, minimize drug–drug interactions, and improve the patient's symptoms and quality of life.

Conclusion

Although polypharmacy and off-label use of medications is common in today's health care environment, nurses need to educate themselves on the risks, benefits, side effects, and FDA-approved indications and off-label uses of psychotropic and other medications. In addition, collaboration among health care professionals is essential to reducing polypharmacy, medication side effects, and drug–drug interactions, while simultaneously improving patient outcomes.

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U.S. FOOD and Drug Administration (FDA)–Approved Indications and off-Label Uses of Common Psychotropic Medications

Medication Class/MedicationFDA Approved IndicationsaOff-Label Usesb
Selective serotonin reuptake inhibitors

Fluoxetine (Prozac®)

Sertraline (Zoloft®)

Paroxetine (Paxil®, Paxil® CR)

Citalopram (Celexa®)

Escitalopram (Lexapro®)

Depression, obsessive compulsive disorder (OCD), generalized anxiety disorder (GAD), premenstrual dysphoric disorder, posttraumatic stress disorder (PTSD), panic disorder, social anxiety disorder, bipolar I disorder, bulimia nervosa (only fluoxetine)

Premature ejaculation, migraine headaches, diabetic neuropathy, vasovagal syncope (Stone, Viera, & Parman, 2003)

Fibromyalgia (Stone et al., 2003; Wittich, Burkle, & Lanier, 2012)

Alcoholism, irritable bowel syndrome, stuttering, pathologic gambling, borderline personality disorder (Wittich et al., 2012)

Other psychiatric conditions for which the drug is not FDA approved

Tricyclic antidepressant agents

Amitriptyline (Elavil®)

Imipramine (Tofranil®)

Doxepin (Sinequan®)

Desipramine (Norpramin®)

Nortriptyline (Pamelor®)

Depression, insomnia (only doxepin)

Bulimia, neuropathic pain, irritable bowel syndrome (Wittich et al., 2012)

Insomnia (Lai, Tan, & Lai, 2011)

Migraine prophylaxis (Stone et al., 2003)

Atypical antipsychotic agents

Quetiapine (Seroquel®)

Olanzepine (Zyprexa®)

Risperidone (Risperdal®)

Aripiprazole (Abilify®)

Schizophrenia, mania, bipolar disorder, adjunctive treatment of depression, treatment of irritability related to autismGAD, eating disorders, OCD, PTSD, substance use disorders, dementia, personality disorders, insomnia (Wittich et al., 2012)
Mood-stabilizing anticonvulsant agents
  Divalproex (Depakote®, Depakote® ER)Epilepsy, seizures, migraine prophylaxis acute mania, bipolar disorder

Schizophrenia, schizoaffective disorder (Horowitz et al., 2014)

  Topiramate (Topamax®)Epilepsy, migraine prophylaxis

Alcohol dependence (Shinn & Greenfield, 2010)

Essential tremor (Chang, Wang, & Chi, 2015)

Weight loss and binge eating disorder (Reas & Grilo, 2015),

Weight gain related to psychotropic agents (Kirov & Tredget, 2005)

  Gabapentin (Neurontin®)Seizures, neuropathic pain, postherpetic neuralgia, restless leg syndrome

Bipolar disorder, fibromyalgia, hot flashes (Wittich et al., 2012); insomnia (Furey, Hull, Leibowitz, Jayawardena, & Roth, 2014)

Antihypertensive agents
  Propranolol (Inderal®)Hypertension, angina, migraine, essential tremor, atrial fibrillation, pheochromocytoma

Migraine prophylaxis (Stone et al., 2003)

Public speaking, GAD, social phobia (Wittich et al., 2012)

Conditioned fear responding (Kindt, Soefer, & Sevenster, 2014)

Autism spectrum disorder (Narayanan et al., 2010)

  Prazosin (Minipres®)Hypertension, benign prostatic hypertrophy

PTSD-related nightmares (Kung, Espinel, & Lapid, 2012)

Agitation in Alzheimer's disease (Wang et al., 2009)

Miscellaneous psychotropic agents
  Buproprion (Wellbutrin® SR/XL, Zyban®)Depression, smoking cessation, seasonal affectivedisorder

ADHD (Berigan, 2002 ; Bidwell, McClernon, & Kollins, 2011; Maneeton, Maneeton, Intaprasert, & Woottiluk, 2014)

Social phobia, PTSD, bipolar disorder, orgasmic dysfunction, cocaine and opiate dependence, hypoactive sexual desire disorder, sexual dysfunction from antidepressant agents (Berigan, 2002)

  Mirtazapine (Remeron®)Depression

Insomnia (Alam, Voronovich, & Carley, 2013; Lai et al., 2011)

Agitation in older adults, anxiety, nausea, alcohol dependence, pain management, increase weight gain (Alam et al., 2013)

  Trazodone (Desyrel®, Oleptra®)Depression

Insomnia (Lai et al., 2011; Wittich et al., 2012)

  Modafinil (Provigil®)Narcolepsy, obstructive sleep apnea, shift work sleep disorder

ADHD (Bidwell et al., 2011)

  Donepezil (Aricept®)Dementia

ADHD (Bidwell et al., 2011)

Frontotemporal dementia (Wittich et al., 2012)

Authors

Dr. Leahy is Family Psychiatric Advanced Practice Nurse and Master Clinician in Psychopharmacology, APNSolutions, LLC, Sewell, New Jersey.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Laura G. Leahy, DrNP, APRN, PMH-CNS/FNP, BC, Family Psychiatric Advanced Practice Nurse and Master Clinician in Psychopharmacology, APNSolutions, LLC, 123 Egg Harbor Road, Suite 703, Sewell, NJ 08080; e-mail: lgleahy@apnsolutions.com

10.3928/02793695-20170210-02

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