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R&D Trends: Depression - Clinical attrition driven by mature market conditions


Review of key trends in the development of new depression drugs across the seven major markets. Also includes detailed analyses of clinical trial design, target product profile, innovative early-stage projects, and future treatment developments.



Several drugs have progressed through the pipeline for depression in recent years, including Pristiq (desvenlafaxine; Pfizer), Oleptro (trazodone extended release; Labopharm), and Viibryd (Forest) in the US, and Valdoxan (agomelatine; Servier/Novartis) in the EU. Despite the heightened competition within the marketplace, an abundance of drugs remain in the pipeline.


  • Understand key dynamics in the R&D pipeline for new depression therapies
  • Benchmark novel and existing therapies using the target product profile identified by Datamonitor
  • Support R&D decision making by evaluating antidepressant clinical trial designs that have set a precedent
  • Evaluate the most promising new pharmacological targets in early-stage development
  • Access Datamonitor's prediction of how the treatment landscape may change in the next 20 years


  • There are 46 separate programs across all stages of clinical development for depression, down from 66 in 2007 with a notably high attrition of early-stage projects. Reasons for this include promising new targets failing to yield an effective antidepressant, and big players such as GlaxoSmithKline switching its research focus.
  • Although depleted, the early-stage pipeline still has the potential to change current treatment algorithms, which are dominated by monoamine reuptake inhibitors. Popular approaches include glutamate and neuropeptide receptor modulation. Datamonitor sees the future of treatment in depression as the specific targeting of treatment-resistant patients.
  • Clinical trial design in depression is largely standardized. Although not required, head-to-head trials may allow for a more favorable label and explicit marketing claims. Datamonitor believes that future trials will be designed for regulatory approval in patients with treatment-resistant depression, or for use as an add-on to existing therapies.


  • What are the key trends in the depression pipeline?
  • What is the clinical gold standard and how do new candidates have to compare to this to successfully penetrate the market?
  • How will new antidepressant treatments evolve in the next 20 years?




  • Summary

    • Strategic scoping and focus
    • Update details: January 2012
    • Datamonitor key findings
    • Related reports


    • Overview of the depression pipeline
    • Datamonitor has identified 46 separate programs in clinical development
    • Emerging features of the depression pipeline
    • Changes in pipeline dynamics
    • Companies involved in the depression pipeline
    • Discontinued pipeline drugs in depression
    • 54 distinct depression projects have been discontinued since 2010
    • The vast majority of discontinuations happen either during preclinical testing or Phase II studies
    • Neuropeptide modulators and monoamine reuptake inhibitors head the list of discontinued projects


    • Comparator therapies
    • Lexapro (escitalopram; Forest/Lundbeck)
    • Target product profile versus current level of attainment


    • Clinical trials
    • Commonly used clinical trial endpoints for depression
    • Typical trial design
    • Trial length is commonly standardized to a duration of just 8 weeks
    • Comparator trials can provide a compelling argument for using one drug ahead of another
    • Future developments in clinical trial design
    • Treatment-resistant depression clinical trial design
    • Adjunctive therapy clinical trial design


    • Glutamate receptor modulation
    • NMDA receptor antagonists and partial agonists
    • Metabotropic glutamate receptor antagonists
    • Targeting neuropeptides for depression
    • Background
    • Vasopressin receptor antagonists
    • Neurokinin receptor antagonists


    • Specific targeting of treatment-resistant patients
    • A label for treatment-resistant depression will bypass competition with generic first-line antidepressants
    • Treatment-resistant depression is characterized by a large target population and substantial unmet need
    • Biomarkers for depression
    • Considerable variations in treatment outcomes exist
    • Biomarkers may have utility in identifying likely responders and improving treatment outcomes
    • The commercial appeal of reduced R&D spend and a competitive advantage is a bonus
    • Biomarkers in clinical development


    • Journal papers
    • Websites
    • Datamonitor reports


    • Contributing experts
    • Conferences attended
    • Report methodology


    • Table: Products in clinical development for depression, January 2012
    • Table: Depression clinical pipeline, by mode of action and development stage, January 2012
    • Table: Discontinued pipeline drugs in depression, 2010-12
    • Table: Discontinued drugs formerly in development for depression, by mode of action and developmental stage, 2010-12
    • Table: Lexapro (escitalopram; Forest/Lundbeck) - drug profile in depression, 2012
    • Table: Defining the gold standard for depression: key clinical trial results for Lexapro
    • Table: Target product profile in major depressive disorder, 2012
    • Table: Comparison between the HAM-D and MADRS rating scales for depression
    • Table: Typical Phase III clinical trial design in major depressive disorder
    • Table: Key facts: Lexapro (escitalopram; Forest/Lundbeck) versus Cymbalta (duloxetine; Eli Lilly) comparator trial in major depressive disorder
    • Table: Key facts: Symbyax (fluoxetine and olanzapine; Eli Lilly) pivotal Phase III clinical trial
    • Table: Key facts: Abilify (aripiprazole; Bristol-Myers Squibb/Otsuka) pivotal Phase III clinical trial
    • Table: Most promising innovative therapeutic approaches in depression, January 2012


    • Figure: Depression clinical pipeline, by developmental stage, January 2012
    • Figure: Depression clinical pipeline, by mode of action, January 2012
    • Figure: Products in clinical development for depression, 2007, 2011, and 2012
    • Figure: Modes of action in the depression pipeline, 2007, 2011, and 2012
    • Figure: Depression pipeline, by developmental stage and company type, January 2012
    • Figure: Big Pharma's involvement in the depression pipeline, January 2012
    • Figure: Discontinued drugs formerly in development for depression, by developmental stage, 2010-12
    • Figure: Modes of action of discontinued pipeline drugs and active pipeline drugs in depression, 2010-12
    • Figure: Head-to-head clinical trial of Lexapro (escitalopram; Forest/Lundbeck) versus Celexa (citalopram; Forest/Lundbeck)
    • Figure: Potential timeline for future depression therapies
    • Figure: Proportion of patients that display treatment-resistant depression (%) in the seven major markets, 2010
    • Figure: BRITE-MD study of the Antidepressant Treatment Response Index as a functional biomarker for depression
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