Treatment Algorithms

August 2010

Treatment Algorithms in Generalized Anxiety Disorder

Report Authors
Amy K. Jassen, Ph.D.
Michael Malecki, Ph.D.

Introduction:

Although there are more than 6 million prevalent cases of generalized anxiety disorder (GAD) in the United States alone, a substantial percentage of newly diagnosed patients do not receive a prescription therapy. Regulatory approval for GAD is generally as a follow-on indication after approval for major depressive disorder (e.g., key branded agents include Lexapro [Forest Laboratories’ escitalopram], Effexor XR [Pfizer’s venlafaxine XR], and Cymbalta [Eli Lilly’s duloxetine]). In our study of newly diagnosed patients, we find these agents are generally reserved for later lines of therapy in favor of generic selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines. Moreover, year-over-year analysis of newly diagnosed GAD patients reveals that branded agents have recently moved backward in lines of therapy, likely because of the increasingly cost-sensitive healthcare environment.

Despite tightening cost restrictions, surveyed primary care physicians (PCPs) and psychiatrists expect to reduce their use of benzodiazepines in GAD over the next two years, likely because of the risk of addiction to these medications. This shift offers an opportunity for agents with a rapid onset of action (relative to antidepressant therapies) for the relief of somatic and/or psychiatric symptoms in GAD without the potential for addiction.

Atypical antipsychotics such as Seroquel/Seroquel XR (AstraZeneca’s quetiapine/quetiapine XR) and Abilify (Bristol-Myers Squibb/Otsuka Pharmaceutical’s aripiprazole) are used in later lines of therapy for the treatment of refractory GAD. However, our drug comparison analysis indicates that a substantial unmet need remains for therapies treating this population, particularly for therapies with new mechanisms of action that can be used either as monotherapy or adjunct therapy to current agents to treat refractory anxiety.

Using patient-level claims data, as well as insight from 151 surveyed psychiatrists and PCPs, this report determines the share of each key therapy used in the treatment of GAD by line of therapy, analyzes why key drugs are chosen over others, and explains how physicians forecast this dynamic will change over the next two years.

Questions Answered in This Report:

  *   Lines of therapy: The GAD market is dominated by generic, off-label benzodiazepines and generic SSRIs (e.g., citalopram [Forest Laboratories’ Celexa, generics], sertraline [Pfizer’s Zoloft, generics]). Our lines of therapy analysis reveals that a considerable percentage of GAD patients progress to second- and third-line therapy, suggesting these generics are insufficient to meet the market needs. Among the major brands approved for GAD, how much use does each brand get in each line of therapy? Why do physicians prescribe one major brand other another? What key messages can each brand use to best expand its market share in GAD?

  *   Pathways to key therapies: For brands relegated to later lines of therapy, longer times before patients progress to these brands mean smaller patient shares. How long do patients progressing to Lexapro, Effexor XR, and Cymbalta remain on their previous therapies? What do the relative times to progression reveal about these key brands? How are these agents placed relative to one another in the treatment algorithm for GAD, and how will their placement evolve over the next two years?

  *   Physician behavior: GAD patients are treated by both psychiatrists and PCPs and can be given different treatments depending on the type of physician. Which group of physicians more often prescribes bupropion (GlaxoSmithKline’s Wellbutrin/Wellbutrin SR/Wellbutrin XL, generics) and why? For which physicians does cost of drugs factor as a more important reason to prescribe one drug over another? What are the weaknesses of each agent treating GAD from the perspective of both psychiatrists and PCPs?

  *   Forecast: Benzodiazepines have been a common first-line therapy for several decades in the treatment of GAD, but surveyed physicians say that their increasing use of combination therapy in the treatment of GAD over the next two years will come with a concomitant decrease in the use of benzodiazepines. Which drugs and drug classes will see the most increased use in early lines of therapy? In which lines of therapy do physicians expect to use new therapies (e.g., PGx Health/Clinical Data, Inc.’s vilazodone, Lundbeck’s LU-AA21004) with potential in the GAD market? What other changes in medical practice will influence future patient share and market dynamics?

Scope:

Primary research: Quantitative results from our survey of 151 physicians (75 psychiatrists and 76 PCPs):

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

- Most influential drug attributes when physicians choose among 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: Lexapro, Effexor XR, Cymbalta, benzodiazepines, citalopram, sertraline, fluoxetine (Eli Lilly’s Prozac, generics), paroxetine (GlaxoSmithKline’s Paxil, generics), bupropion (GlaxoSmithKline’s Wellbutrin/Wellbutrin SR/Wellbutrin XL, generics), venlafaxine IR (Pfizer’s [formerly Wyeth’s] Effexor, generics), Pristiq (Pfizer/Impax Laboratories’ desvenlafaxine XR), Seroquel, buspirone (Bristol-Myers Squibb’s BuSpar, generics), mirtazapine (Organon’s Remeron, generics), gabapentin (Pfizer’s Neurontin, generics), hydroxyzine pamoate (generics), hydroxyzine hydrochloride (generics), other antiepileptics (generics), tricyclic agents (generics), and modified cyclics (generics).

- Flowcharts tracking the preceding therapy patterns for patients taking each of the following key therapies: Lexapro, Effexor XR, Cymbalta, benzodiazepines, citalopram, sertraline, fluoxetine, paroxetine, venlafaxine IR, Pristiq, Seroquel, Seroquel XR, Abilify, risperidone, Zyprexa, buspirone, mirtazapine, and Lyrica (Pfizer’s pregabalin).

Search Reports

Mentioned in this report:

  • - AstraZeneca
  • - Bristol-Myers Squibb
  • - Clinical Data, Inc.
  • - Eli Lilly
  • - Forest Laboratories
  • - GlaxoSmithKline
  • - Impax Laboratories
  • - Janssen
  • - Lundbeck
  • - Organon
  • - Pfizer
  • - PGx Health
  • - Takeda Pharmaceutical