Management of antipsychotic medication polypharmacy

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Within our healthcare-driven society, the increase in the identification and diagnosis of mental illnesses has led to a proportional increase in the prescribing of psychotropic medications. The prevalence of mental illnesses and subsequent treatment approaches may employ monotherapy as first-line treatment, but in many cases the use of combination of therapy can occur, leading to polypharmacy.1 Polypharmacy can be defined in several ways but it generally recognized as the use of multiple medications by one patient and the most common definition is the concurrent use of five more medications. The presence of polyharmacy has the potential to contribute to non-compliance, drug-drug interactions, medication errors, adverse events, or poor quality of life.

Within our healthcare-driven society, the increase in the identification and diagnosis of mental illnesses has led to a proportional increase in the prescribing of psychotropic medications. The prevalence of mental illnesses and subsequent treatment approaches that employ monotherapy as first-line treatment, but in many cases the use of combination of therapy can occur, leading to polypharmacy.1 Polypharmacy can be defined in several ways but it is generally recognized as the use of multiple medications by one patient and the most common definition is the concurrent use of five more medications.1,2 The presence of polyharmacy has the potential to contribute to non-compliance, drug-drug interactions, medication errors, adverse events, or poor quality of life.2,3 Individuals with mental impairments or developmental delays residing in supported living centers may be placed on a number of psychotropic medications intended to manage aggression, agitation, mood, or behavioral or psychiatric disturbances; the failure to engage in the regular monitoring of these medications is recognized as the most frequent cause of preventable adverse drug events, particularly with antipsychotic medications.4 The customary standard of practice with antipsychotic medication initiation is to start with one medication and monitor for tolerability, the development of side effects (e.g., weight gain and metabolic profiles), and determination of efficacy after an optimal duration of therapy (Table 1).5 Once the initial antipsychotic medication trial fails to achieve a therapeutic response, prescribers can turn to the use of combination therapy, which is an increasingly common practice in the treatment of schizophrenia and other psychotic disorders.6

While data are lacking to support this trend, there are reports that describe the use of high- and low-potency neuroleptics as a method for balancing side effects and maintaining efficacy.7 The underlying assumption for this clinical practice is that if one agent does not achieve the desired therapeutic outcome for controlling positive and/or negative symptoms, another medication within the same class can be added, but this practice in turn can lead to polypharmacy.8 Although expert consensus guidelines do not advocate antipsychotic polypharmacy, some view this practice as a last resort after prior monotherapy alternatives have been attempted.8 There are various reasons why antipsychotic polypharmacy can be used, with one of the most common being to increase effectiveness in treating patients with refractory psychotic symptoms, mood symptoms, or behavioral disturbances.8,9 Additionally, antipsychotic polypharmacy is heavily driven by the availability of pharmacologically diverse atypical antipsychotics, and the concurrent use of more than one antipsychotic medication can vary from 13% to 60% based on the studied population.9,10

Even though antipsychotic medications are widely prescribed and demonstrate efficacy in the management of psychotic symptoms, they have potential to cause weight gain and its sequelae of hyperglycemia, hypertension, and hyperlipidemia, particularly atypical antipsychotics.11 The atypical antipsychotics are associated with a reduced risk of extrapyramidal side effects (e.g., dystonia, tardive dyskinesia) or hypotensive events when compared to the typical antipsychotics, but can be associated with a metabolic risk (Table 2).12 It has been proposed that the illness, antipsychotic medication side effects, along with smoking, diet, and other poor lifestyle choices can place this population at great risk for cardiovascular disease.13 While atypical antipsychotics are associated with these adverse effects, they remain as the key treatment options in schizophrenia and other major psychotic disorders.14 The identification of antipsychotic medication polypharmacy and potential risk in populations with mental impairments and developmental delays are all the more important because adverse effects may go unrecognized.14 Due to the limited research or clinical trials on the use of psychotropic medications in this particular population, problems can be encountered when multiple psychotropic medications within the same drug class are prescribed.15 The rate of psychiatric disorders among individuals with mental impairments and developmental delays is reported to range from 10% to 30%, with behavioral disturbances exceeding 10%, and 22% receiving antipsychotic medications.16,17

To ensure that antipsychotic medications as well as other psychotropic medications are prescribed appropriately, it is recommended that a medication should be indicated for four broad reasons: 1) to enhance habilitative or educational function, 2) to treat specific psychiatric disorders, 3) for immediate control of dangerous behaviors, and 4) for control of severe disruptive behaviors that fail to respond to behavioral interventions. The prescription of any psychotropic medication requires identification and documentation of specific target symptoms or behaviors manifest by the patient as well as assessment of efficacy for symptom reduction.17 It is generally when prescribing falls out of the scope of these four indicated areas that polypharmacy can occur, leading to unnecessary expenses, wasted time, and possibly mismanagement of regimen.17 The appropriate use of antipsychotic medications in this population requires an accurate and evidence-based diagnosis that justifies the use of each medication that is initiated. From a managed care perspective, the collaborative efforts between the healthcare professionals who are involved in the treatment of these patients can assess the presence of documented clinical justification for the initiation of additional antipsychotic medications.18 For example, the performance of medical reviews by pharmacists engaged in a multidisciplinary team approach with nursing staff, physicians, and other relevant health professionals can help to reduce inappropriate antipsychotic medication use and prevent polypharmacy.18 Additionally, the continuous monitoring of antipsychotic prescribing patterns, the delivery of educational in-services, and promotion of interprofessional practice to increase appropriate drugs use can lay the groundwork for future changes to be made in clinical practice guidelines. There may be varying opposing perspectives on the monitoring of antipsychotic polypharmacy and the resultant outcomes.19 While some opponents may view these changes as restrictions on prescriber’s autonomy and limitations being placed on drug selections, proponents may view this as measures that are warranted to ensure patient safety and improvement of healthcare services.19

The decision to initiate any psychotropic medication, especially an antipsychotic medication, is one that involves a discussion between the prescriber and the patient. Given the associated side effects/adverse events, it is important that the risks versus benefits of therapy and the potential development of polypharmacy be thoroughly assessed on an ongoing basis.

References

1.     Masoodi, M. Polypharmacy: To err is human to correct divine. BJMP. 2008;1(1):6-9.

2.     Hamza S, Abdelwadoud M, Kandil I, Mortagy A. Polypharmacy and inappropriate medication use among elderly persons in an Egyptian rural area. Middle East Journal of Age & Ageing [serial online]. 2012;9(1):13-19.

3.     Nguyen JK, Fouts MM, Kotabe SE. Polypharmacy as a risk factor for adverse drug reactions in geriatric nursing home residents. Am J Geriatric Pharmacotherapy. 2006;4:36-41.

4.     Feldstein AC, Smith DH, Perrin N, et al. Improved therapeutic monitoring with several medications: A randomized trial. Arch Intern Med. 2006;166:1848-1854.

5.     Thompson A, Hetrick S, McGorry P, et al. Targeted intervention to improve monitoring of antipsychotic-induced weight gain and metabolic disturbance in first episode psychosis. Australian & New Zealand Journal of Psychiatry. 2011;45(9):740-748.

  6.    Clark R, Bartels S, Mellman T, Peacock W. Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorders: Implications for state mental health policy. Schizophren Bull. 2002;28(1):75-84.

7.      Godleski LS, Kerler R, Barber JW, Glick JL, Kellogg E, Vieweg WV, Yank GR. Multiple versus single antipsychotic drug treatment in psychosis [Letter]. J Nerv Mental Dis. 1989;177(11):686-689.

8.     Faries D, Ascher-Svanum H, Baojin Z, Correll C, Kane J. Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics. BMC Psychiatry. 2005;5:26.

9.     Tapp A, Wood AE, Secrest L, Erdmann J, Cubberley L, Kilzieh N. Combination antipsychotic therapy in clinical practice. Psychiatr Serv. 2003;54:55-59.

10.   Covell NH, Jackson CT, Evans AC, Essock SM. Antipsychotic prescribing practices in Connecticut’s Public Mental Health System: Rates of changing medications and prescribing styles. Schizophren Bull. 2002;28:17-29.

11.   Lambert T. Managing the metabolic adverse effects of antipsychotic drugs in patients with psychosis. Australian Prescriber 2011;34(4):97-99.

12. Newcomer J, Haupt D. The metabolic effects of antipsychotic medications. Can J Psychiatry. 2006;51(8):480-491.

13. Hennekens CH. Increasing global burden of cardiovascular disease in general populations and patients with schizophrenia. J Clin Psychiatry. 2007;68 Suppl:4-7.

14. Haddad P, Sharma S. Adverse effects of atypical antipsychotics: Differential risk and clinical implications. CNS Drugs. 2007;21(11):911-936.

15. De Bildt A, Mulder EJ, Scheers T, Minderaa RB, Tobi H. Pervasive developmental disorder, behavior  problems, and psychotropic drug use in children and adolescents with mental retardation. Pediatrics.  2006;118:1860-1866.

16. Spreat C, Conroy JW, Jones JC. Use of psychotropic medication in Oklahoma: a statewide survey. Am J Mental Retardation 1997;102(1):80-85.

17. Powers RE. General principles of clinical psychopharmacology for persons with mental retardation/developmental disabilities (MR/DD). DDMED 27 Bureau of Geriatric Psychiatry 2005:1-15.

18. Centre for Reviews and D. Effect of interventions to reduce potentially inappropriate use of medicines in nursing homes: a systematic review of randomised controlled trials (Structured abstract). 2010. Available from: Health Technology Assessments, Ipswich, MA.

19. Baker J. Multi-disciplinary perceptions of patient group directions as a replacement for the pro re nata prescribing of antipsychotic medications in acute mental health settings. J Adv Nurs. 2011;67(10):2191-2199

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