Treatment Algorithms

November 2010

Treatment Algorithms in Bipolar Disorder

Report Authors
Alana Simorellis, Ph.D.
Michael Malecki, Ph.D.

Introduction:

Bipolar disorder (BPD) is a chronic and debilitating psychiatric illness. Relatively mild patients may experience subthreshold hypomanic and subthreshold depressive symptoms, while other patients experience acute manic and major depressive episodes. Treatment consists of addressing acute mood episodes and preventing further mood episodes. Lithium, antidepressants, antiepileptics, and atypical antipsychotics (particularly AstraZeneca/Astellas’s Seroquel, AstraZeneca’s Seroquel XR, Bristol-Myers Squibb/Otsuka’s Abilify, and Eli Lilly’s Zyprexa), often taken in combination, are the mainstay of treatment for BPD. Physicians must carefully balance efficacy of current agents with their safety profiles because atypical antipsychotics, lithium, and antiepileptics are associated with several tolerability concerns. The balance between efficacy and safety continues to drive changes in prescribing trends. Lithium and antiepileptics have demonstrated efficacy in BPD, particularly lamotrigine (GlaxoSmithKline’s Lamictal, generics), which many physicians prescribe to prevent depressive episodes. Historically, primary care physicians (PCPs) are less comfortable prescribing these therapies, which require careful titration and monitoring. Over the past year, a larger proportion of the physicians we surveyed for this year have increased their use of atypical antipsychotics despite the risk of metabolic and weight gain side effects associated with the use of these drugs. Of the atypical antipsychotics, Abilify and Pfizer’s Geodon (ziprasidone) are perceived to be associated with a lower propensity to induce weight gain relative to Seroquel/Seroquel XR and Zyprexa; however, Seroquel/Seroquel XR and Zyprexa are viewed as highly efficacious, particularly for depressive and manic episodes, respectively.

The Treatment Algorithms in Bipolar Disorder report analyzes patient-level claims data to quantify BPD drug share by line of therapy in newly diagnosed patients and identifies, through our survey of 159 U.S. physicians (79 psychiatrists and 80 PCPs), physicians’ preferred first-line treatments for key segments of the BPD population (e.g., acute mania, acute depression, and maintenance). These data identify the patient segments that drive each agent’s patient share in each line of therapy. Our primary research also shows which drug attributes are most important to physicians in first-line therapies for acute mood episodes and maintenance treatments and juxtaposes how each agent performs on each of these attributes versus their patient shares by line of therapy; using these leverage points, brand sales and marketing teams can effectively build strategies for taking share from competitors or building share in untapped areas of the BPD market.

Questions Answered in This Report:

  *   Lines of therapy: Treatment of BPD patients depends on the phase of the illness. Patients can present with acute hypomania, manic, depressive, or mixed mood episodes. In between mood episodes, treatment consists of maintenance therapy. Lithium, antiepileptics, antidepressants, and atypical antipsychotics, often taken in combination, are the mainstay of treatment for BPD. What therapies are preferred for first-line treatment for mood episodes and maintenance therapy? What classes of therapies are preferred for manic or depressive episodes? How much early-line patient share is devoted to agents that are most likely to be prescribed for patients presenting with acute mania (e.g., lithium, Zyprexa, divalproex [Abbott’s Depakote/Depakote ER, generics]) versus agents that are also targeting depressive symptoms (e.g., antidepressants, lamotrigine, Seroquel, Abilify)? How frequently do surveyed physicians prescribe a generic as a first-line agent over its branded competitors (e.g. risperidone [Janssen’s Risperdal, generics] versus a branded atypical antipsychotic)?

  *   Pathways to key therapies: Atypical antipsychotics are primarily differentiated by physician perceptions of their efficacy in treating manic or depressive symptoms and prevention of relapses as well as the agent’s risk of weight gain and metabolic side effects. Which atypical antipsychotics receive more of their total use as first-line therapy? What percentage of Abilify users move to it directly after Seroquel, and vice versa? What is the preferred line of therapy for Geodon? What agents precede use of Geodon?

  *   Physician behavior: Consistent with our previous analysis, PCPs play an important role in diagnosing and prescribing early-line therapies for BPD, particularly PCPs who are comfortable prescribing atypical antipsychotics. What attributes drive PCPs’ choices for first-line acute mood episodes and first-line maintenance treatment? Do psychiatrists differentiate between branded atypical antipsychotics? Which agents do each physician type prefer for first-line treatment of acute mood episodes or maintenance treatment?

  *   Forecast: Emerging therapies of interest expected to launch over the next two years with a bipolar indication include Merck/Lundbeck’s lurasidone and Alexza Pharmaceutical’s AZ-004. Merck’s recently launched Saphris (launched in 2009), as well as the continuing uptake of Seroquel/Seroquel XR and Invega (Janssen’s paliperidone ER), could expand the BPD market. However, in the same time period, generic formulations of olanzapine, quetiapine, ziprasidone, and paliperidone ER (starting in 2011) will join generic divalproex semisodium ER and DR, lamotrigine, and risperidone (all of which launched in 2008-2009) in contributing to the contraction of this market. To what extent will physicians prescribe the upcoming generics and at the expense of which therapies between now and 2012? Which emerging therapies do they collectively cite as having the most potential to gain use for BPD?

Scope:

Primary research: Quantitative results from our survey of 159 physicians (79 psychiatrists and 80 PCPs):

- Physician opinion on how drug use differs by patient severity.

- Most influential drug attributes when physicians choose between agents.

- Anticipated changes in the line of therapy in which physicians use key agents.

Primary patient-level data: Quantitative findings from our analysis of data covering 61 million lives from 98 geographically diverse U.S. health plans:

- Quantified lines of therapy analysis showing exact share of each agent in each line of therapy, including rate of progression between lines and length of time patients are on each line.

- Progression flowcharts through one year of treatment for newly diagnosed patients receiving each of the following first line agents: Seroquel, Abilify, Zyprexa, Geodon, Invega, Janssen’s Risperdal Consta, Janssen’s Invega Sustenna, Saphris, risperidone, divalproex DR, divalproex semisodium ER, other valproic acid, lamotrigine, carbamazepine, gabapentin, Pfizer’s Lyrica, other antiepileptic drugs, lithium, typical antipsychotics, Eli Lilly’s Symbyax, benzodiazepines, Forest/Lundbeck’s Lexapro, other selective serotonin reuptake inhibitors (SSRIs), Eli Lilly’s Cymbalta, Pfizer’s Effexor XR, venlafaxine IR, mirtazapine, tricyclic agents, trazodone, and bupropion.

- Flowcharts tracking the preceding therapy patterns for patients taking each of the following key therapies: Seroquel, Seroquel XR, Abilify, Zyprexa, Geodon, Invega, Saphris, risperidone, divalproex DR, divalproex ER, other valproic acid, lamotrigine, gabapentin, Lyrica, carbamazepine, and lithium.


Search Reports

Mentioned in this report:

  • - Abbott
  • - Alexza
  • - Astellas
  • - AstraZeneca
  • - Bristol-Myers Squibb
  • - Dainippon Sumitomo
  • - Janssen Pharmaceutica
  • - Eli Lilly
  • - Lundbeck
  • - Merck
  • - Novartis
  • - Otsuka
  • - Pfizer
  • - Sunovion Pharmaceuticals
  • - Vanda
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