Report: Stakeholder Insight: Major Depressive Disorder - Duloxetine

ABOUT DATAMONITOR HEALTHCARE
- About the CNS pharmaceutical analysis team
CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the Major Depressive Disorder (MDD) market
- Individuals with milder forms of Major Depressive Disorder are unlikely to present to physicians. Across the seven major markets, only around a half of individuals are then accurately diagnosed at first presentation.
- The safety concerns surrounding antidepressants have been over-hyped and are not generally shared by physicians.
- Cymbalta (duloxetine) is at risk of being seen as a 'me-too' SNRI. Datamonitor's primary research suggests that by focusing on the treatment of painful physical symptoms of depression, Lilly might be missing the drug's more significant advantages.
CHAPTER 2 INTRODUCTION AND SCOPE
- Coverage of the Stakeholder Insight survey - MDD
  - Epidemiology
  - Presentation and diagnosis
  - Treatment of Major Depressive Disorder
CHAPTER 3 COUNTRY TREATMENT TREES
- Country treatment trees
CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION OF MDD
- Major Depressive Disorder: definitions and classification
  - Diagnostic criteria of MDD
    - DSM-IV
    - ICD-10
    - Severity
    - Dysthymic disorder is a milder form of depression
- Etiology of Major Depressive Disorder
- Epidemiology of MDD
  - Prevalence of MDD
- Segmentation of MDD
  - Prevalence of MDD subtypes
  - Comorbidities
    - Anxiety
    - Cancer and other serious illnesses can be accompanied by depression
    - Heart disease
    - Diabetes
    - Neurodegenerative diseases
CHAPTER 5 PRESENTATION & REFERRAL
- Presentation rates for milder forms of MDD are low suggesting a significant untreated patient population may exist
- The PCP is the first contact for the majority of MDD patients
- PCPs opt to refer the patients as MDD severity increases
- Greater patient awareness may result in greater numbers seeking help
  - Further use of internet-based screeners could increase presentation rates.
CHAPTER 6 DIAGNOSIS OF MDD
- A number of diagnostic tools are available to ensure correct diagnosis on presentation
  - WHO-Five Well-being Index provides a useful screener for the suspected depression
  - The Major Depression Inventory is recommended for use in diagnosing MDD
  - Clinical trials or epidemiological studies require more advanced diagnostic tools
    - The Hamilton Rating Scale for Depression (HAM-D) is the gold standard used in clinical trials.
    - The CIDI is favored for epidemiologic studies
  - Diagnosis of MDD can be confused with bipolar disorder
- Diagnosis rate of MDD
  - Interviewed physicians ask about the key symptoms when making a diagnosis of MDD.
  - Painful physical symptoms are often associated with depression
CHAPTER 7 TREATMENT GUIDELINES
- Treatment guidelines aim to improve treatment outcomes but are underused outside of the US.
  - Updates to the APA guideline cover recent issues.
  - The NICE guideline includes cost-benefit assessment.
CHAPTER 8 TREATMENTS AVAILABLE
- Choice of treatment modality is key to the treatment outcome
  - Treatments already tried depend on the severity of depression
  - Treatments chosen by interviewed physicians
- Drug class overview
  - MAOIs and TCAs-effective but potentially unsafe.
  - SSRIs avoid the problems of earlier antidepressants.
    - Prozac (fluoxetine)
    - Zoloft (sertraline)
    - Celexa (citalopram)
    - Lexapro (escitalopram)
    - Luvox (fluvoxamine)
    - Paxil (paroxetine)
  - SNRIs have added a new layer of available treatment options
    - Effexor (venlafaxine)
    - Cymbalta (duloxetine)
  - Other drugs have proven effective in treating MDD
    - Wellbutrin (bupropion)
    - Remeron (mirtazapine)
    - Ixel (milnacipran)
    - Edronax (reboxetine)
    - Serzone (nefazodone)
    - St.John's Wort (Hypericum perforatum)
- Non-pharmacological treatment overview
  - Psychotherapy
    - Cognitive behavioral therapy
  - Electroconvulsive therapy (ECT)
CHAPTER 9 PRESCRIBING TRENDS
- Choice of prescribed drug class
  - TCAs and SSRIs are prescribed to the majority of patients
- Choice of prescribed drugs
  - Drug choices by US physicians
    - Key prescribing trends in the US
  - Drug choices by physicians in Japan
    - Key prescribing trends in Japan
  - Drug choices by physicians in France
    - Key prescribing trends in France
  - Drug choices by physicians in Germany
    - Key prescribing trends in Germany
  - Drug choices by physicians in Italy
    - Key prescribing trends in Italy
  - Drug choices by physicians in Spain
    - Key prescribing trends in Spain
  - Drug choices by UK physicians
    - Key prescribing trends in the UK
- First-line to second-line progression
- Second to third line progression
- Reasons for switching treatment
CHAPTER 10 FACTORS INFLUENCING PRESCRIBING TRENDS
- Choice of therapy - drug attributes
  - Efficacy
  - Side effects
    - Sexual dysfunction
    - Weight gain
    - Sleep problems
    - GI effects
  - Safety profile
    - Risk of suicide
    - Cardiovascular (CV) risks
    - Warnings given to patients
  - Comorbid anxiety
  - Ability to treat painful physical symptoms of depression
- Other factors
  - Branded versus generic
CHAPTER 11 IMPROVING TREATMENT OUTCOMES
- Optimum duration of therapy
- Remission and relapse
  - Proportion of patients achieving remission
  - Time to achieve remission
  - Proportion of patients who relapse during remission
- Unmet needs
APPENDIX A
- Bibliography
- Websites
APPENDIX B
- Physician research methodology
- Physician sample breakdown
  - US
  - Japan
  - France
  - Germany
  - Spain
  - Italy
  - UK
- Physician questionnaire
  - Section One Epidemiology and presentation
    - Epidemiology
    - Presentation and diagnosis
  - Section Two Referral patterns
  - Section Three Treatment
    - Guidelines
    - All treatments
    - Pharmacological treatment
    - Treatment of Mild Major Depressive Disorder
    - Treatment of Moderate Major Depressive Disorder
    - Treatment of Severe Major Depressive Disorder
    - General
  - Section Four Drug profiles
APPENDIX C
- About Datamonitor
  - About Datamonitor Healthcare
  - About the CNS analysis team
- Disclaimer
List of Tables
- Table 1: Total adult population in the seven major markets, (millions)
- Table 2: Adult MDD population estimates using 12-month prevalence, (millions)
- Table 3: The number of individuals suffering from each MDD severity, (millions)
- Table 4: Antidepressants approved for anxiety disorders in the US, EU and Japan
- Table 5: Search engine hits for "Depression".
- Table 6: Average time taken for MDD patients to achieve remission
- Table 7: Average time taken for MDD patients to relapse
- Table 8: US physician sample breakdown, 2005
- Table 9: Japan physician sample breakdown, 2005
- Table 10: France physician sample breakdown, 2005
- Table 11: Germany physician sample breakdown, 2005
- Table 12: Spain physician sample breakdown, 2005
- Table 13: Italy physician sample breakdown, 2005
- Table 14: UK physician sample breakdown, 2005
List of Figures
- Figure 1: The presentation, diagnosis and treatment of MDD in the US
- Figure 2: The presentation, diagnosis and treatment of MDD in Japan
- Figure 3: The presentation, diagnosis and treatment of MDD in France
- Figure 4: The presentation, diagnosis and treatment of MDD in Germany
- Figure 5: The presentation, diagnosis and treatment of MDD in Italy
- Figure 6: The presentation, diagnosis and treatment of MDD in Spain
- Figure 7: The presentation, diagnosis and treatment of MDD in the UK
- Figure 8: Interviewed physicians' estimate of MDD prevalence
- Figure 9: Physicians' perception of the severity of patients suffering from MDD across the seven major markets
- Figure 10: Proportion of patients with mild, moderate and severe MDD that present to a physician.
- Figure 11: Percentage of MDD patients who consult PCPs directly across the seven major markets
- Figure 12: Percentage of patients who consult psychiatrists directly across the seven major markets
- Figure 13: Healthcare professional types referring to psychiatrists across the seven major markets.
- Figure 14: Percentage of interviewed physician's patients referred to another healthcare professional.
- Figure 15: Referral of mild MDD patients to other healthcare professionals.
- Figure 16: Referral of moderate MDD patients to other healthcare professionals.
- Figure 17: Referral of severe MDD patients to other healthcare professionals.
- Figure 18: Proportion of patients with mild, moderate and severe MDD that receive an accurate diagnosis at first presentation
- Figure 19: Symptoms asked about by physicians prior to making a diagnosis of MDD
- Figure 20: Patients reporting painful physical symptoms associated with their depression
- Figure 21: Patients reporting painful physical symptoms associated with their depression to interviewed PCPs and psychiatrists
- Figure 22: Use of recognized practice guidelines according to interviewed physicians across the seven major markets
- Figure 23: Relative use of guidelines for the treatment of MDD by interviewed physicians in the US
- Figure 24: Treatment already tried when patients first present to psychiatrists
- Figure 25: Treatment already tried when mild MDD patients first present to psychiatrists
- Figure 26: Treatment already tried when moderate MDD patients first present to psychiatrists
- Figure 27: Treatment already tried when severe MDD patients first present to psychiatrists
- Figure 28: Types of treatment chosen for MDD patients by physicians
- Figure 29: APA guideline - Choice of treatment modalities for MDD
- Figure 30: Types of treatment chosen for mild MDD patients
- Figure 31: Types of treatment chosen for moderate MDD patients
- Figure 32: Types of treatment chosen for severe MDD patients
- Figure 33: Drug classes prescribed to MDD patients as monotherapy
- Figure 34: Drug classes prescribed to mild MDD patients
- Figure 35: Drug classes prescribed to moderate MDD patients
- Figure 36: Drug classes prescribed to severe MDD patients
- Figure 37: Drugs chosen for MDD by physicians in the US
- Figure 38: Drugs chosen for MDD by physicians in Japan
- Figure 39: Drugs chosen for MDD by physicians in France
- Figure 40: Drugs chosen for MDD by physicians in Germany
- Figure 41: Drugs chosen for MDD by physicians in Italy
- Figure 42: Drugs chosen for MDD by physicians in Spain
- Figure 43: Drugs chosen for MDD by physicians in the UK
- Figure 44: The proportion of MDD patients that progress from first to second-line therapy
- Figure 45: Time taken before physicians decide to progress MDD patients from first to second-line therapy
- Figure 46: The proportion of MDD patients that progress from second to third-line therapy
- Figure 47: Time taken before physicians decide to progress MDD patients from second to third-line therapy
- Figure 48: The reasons for switching patients from first-line treatment
- Figure 49: Influence on physicians' choice of therapy
- Figure 50: Overall efficacy rating according to interviewed physicians.
- Figure 51: Physicians' rating of overall side effect profile
- Figure 52: Influence of side effects on physicians' choice of therapy
- Figure 53: Physicians' concern about the occurrence of sexual dysfunction
- Figure 54: Physicians' concern about the occurrence of weight gain
- Figure 55: Physicians' concern about the occurrence of insomnia
- Figure 56: Physicians' concern about the occurrence of GI effects
- Figure 57: Rating of good safety profile according to interviewed physicians
- Figure 58: Physicians' concern about risk of suicidal ideation
- Figure 59: The black box warning added to all antidepressants in the US
- Figure 60: Physicians that have changed their prescribing habits as a result of reports suggesting a link between antidepressant use and increased risk of suicidality
- Figure 61: The warnings given by physicians to patients when initiating treatment with an antidepressant
- Figure 62: Ability to treat comorbid anxiety disorders according to interviewed physicians
- Figure 63: Ability to treat painful physical symptoms of depression according to interviewed physicians
- Figure 64: Lilly's Cymbalta website-www.depressionhurts.com
- Figure 65: The proportion of prescriptions for which physicians specify use of a generic product when branded version is also available
- Figure 66: Optimum time period for MDD patients on pharmacological therapy (weighted score)
- Figure 67: Optimum time period for mild MDD patients on pharmacological therapy
- Figure 68: Optimum time period for moderate MDD patients on pharmacological therapy
- Figure 69: Optimum time period for severe MDD patients on pharmacological therapy
- Figure 70: Patients achieving remission after one treatment cycle
- Figure 71: Weighted scores for the average time taken for MDD patients to achieve remission
- Figure 72: Patients who relapse during remission
- Figure 73: Unmet needs rated by interviewed physicians as the most important

Stakeholder Insight: Major Depressive Disorder - Duloxetine - Fulfilling An Unmet Need?

Table of Contents