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Challenges in the Management of Agitation Associated with Schizophrenia and Bipolar Disorder

Pharmacist Perspective
Faculty Perspectives: Similarities and Differences in Agitation Associated with Schizophrenia and Bipolar Disorder

Agitation associated with schizophrenia and bipolar disorder can create dangerous situations for patients and caregivers1,2 and is one of the leading contributors of direct medical costs, including emergency department visits and hospitalizations.1,3 Therefore, the treatment of agitation should be a management priority, with the goals of alleviating disease-related symptoms, reducing overall costs, and improving patients’ quality of life.

The main article in this supplement summarizes the characteristics of schizophrenia and bipolar disorder, and discusses the impact of agitation on disease management. The author also emphasizes the importance of a differential diagnosis due to other potential causes of agitation such as akathisia or medication use.1,4 Since some of these medications may be the same ones used to treat schizophrenia and bipolar disorder, it is important to be aware of their limitations, which may include delayed onset of action, route of administration, and adverse events. Careful consideration is required when selecting an atypical antipsychotic agent with efficacy for agitation as monotherapy compared with adding an adjunctive therapy, based on factors such as additive adverse events, drug interactions, compliance, and cost. In addition, when treating patients, there are clinical and financial considerations regarding additive/adjunctive/combination therapy versus monotherapy. Monotherapy may do a better job of treating agitation, but it may not be as effective for treating schizophrenia or bipolar disorder. Therefore, appropriate drug–drug therapy needs to be evaluated for each patient. Newer formulations of antipsychotics are helping to address some of the shortcomings we have seen with standard therapies.

Agitation may manifest itself differently in schizophrenia than in bipolar disorder, but the treatment approach is generally the same.5 From a payer perspective, we do not have the ability to differentiate via claims data; therefore, medications are managed with a population-based, high-level approach. Schizophrenia and bipolar disorder are often difficult to treat, with significant clinical sequelae and costs. Additionally, it is challenging for managed care organizations, especially pharmacy departments, to validate the prevalence and costs of schizophrenia and bipolar disorder because pharmacy claims are not associated with diagnosis codes and many of the antipsychotics are used off-label. As a result, payers may not be aware of the true impact of these conditions within their patient populations. Furthermore, because of the lack of integration between pharmacy claims and medical claims, it is difficult to differentiate between the 2 disease states. Although the treatment of schizophrenia and bipolar disorder relies heavily on pharmacotherapy, specifically antipsychotics, it is challenging for payers to compare the medications used to treat these conditions. Ultimately, when a Pharmacy and Therapeutics Committee is tasked with evaluating therapies for formulary inclusion, they must make several assumptions based on indirect comparisons of efficacy, safety, cost, and indications.

In summary, although the management approaches for patients with schizophrenia and bipolar disorder are similar, there are differences between the two. When the role of agitation is factored in, appropriate treatment becomes even more complicated. Further education regarding these diseases and their associated costs is needed, as are more therapeutic options with measurable data of cost-effectiveness.


1. Citrome L. Addressing the need for rapid treatment of agitation in schizophrenia and bipolar disorder: focus on inhaled loxapine as an alternative to injectable agents. Ther Clin Risk Manag. 2013;9:235-245.
2. Bourget D, el-Guebaly N, Atkinson M. The CPA’s Practice Research Net­work - part IV: assessing and managing violent patients. Bull Can Psychiatr Assoc. 2002;34:25-27.
3. Maj M, Pirozzi R, Magliano L, et al. Agitated depression in bipolar I disorder: prevalence, phenomenology, and outcome. Am J Psychiatry. 2003;160:2134-2140.
4. Advokat C. A brief overview of iatrogenic akathisia. Clin Schizophr Relat Psychoses. 2010;3:226-236.
5. Schleifer JJ. Management of acute agitation in psychosis: an evidence-based approach in the USA. Adv Psychiatr Treat. 2011;17:91-100.

Last modified: August 30, 2021