Clinical Presentation Worry about: health job and finances competence acceptance family, friends, relationships minor matters Unexplained physical symptoms

Most Patients with GAD do NOT Present with Anxiety as the Primary Complaint (part of the reason for under-diagnosis) Only 13% had anxiety as primary complaint This slide shows data from the Generalized Anxiety and Depression in Primary Care (GAD-P) study, which involved 558 primary care physician practices in Germany. All patients who consulted any of these physicians on a single study day were asked to complete a symptom screening questionnaire which was used to diagnose GAD and major depressive episodes (MDE) as defined by DSM-IV criteria. (MDE occurs in Major Depressive Disorder and may also be present in disorders such as Bipolar Disorder and Schizoaffective Disorder.) The physicians were asked to complete a clinical appraisal questionnaire for each patient, in which they gave a diagnostic appraisal of the mental and physical problems of the patient, along with information about treatments provided. Symptoms and diagnosis of GAD (DSM-IV) were assessed using the Generalized Anxiety Screening Questionnaire, and a modified version of the Anxiety Screening Questionnaire. These instruments served as the diagnostic gold standard for determining the presence of GAD in this setting. Over 20,000 patients completed the questionnaire and full information was available on 17,739 of these. The key talking points on this slide are as follows: Of the patients diagnosed with GAD in this study, only 13% described anxiety as their primary complaint. Half the patients with GAD presented with somatic (medical) illnesses and complaints. Pain and sleep disturbance were also two common primary complaints described by patients. Reference Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34 Based on sample of n=17,739; 5.3% with GAD (DSM-IV) Wittchen et al. J Clin Psychiatry. 2002;63(suppl 8):24-34 2

GAD in Primary Care Often under-diagnosed or significant time lag before correct diagnosis Often available effective treatments are not used due to lack of knowledge!

Substance use disorders Patients† with lifetime prevalence* of GAD will commonly report other disorders Anxiety disorders Mood disorders In an analysis of surveys from four countries (Brazil, Canada, the Netherlands and the United States) including over 20,000 individuals aged 18 years, the pattern of comorbidity in patients with GAD was determined The Composite International Diagnostic Interview administered by a lay interviewer was used to assess DSM-III-R anxiety, mood and substance use disorders in these surveys The combined total lifetime prevalence estimates of GAD across all four countries was 3.9% Of the individuals with GAD, 88.3% reported suffering from any comorbid disorder (agoraphobia, panic disorder, simple phobia, social phobia), mood disorders (dysthymia, major depression, mania) or substance use disorders (substance abuse or dependence) Social phobia was a commonly reported comorbid anxiety disorder in individuals with GAD (34%) Panic disorder was identified in 21.8% of GAD patients The most commonly reported comorbid mood disorders were major depression (60.9%) and dysthymia (37.7%) Approximately one-third of individuals with a history of GAD also reported a history of substance abuse or dependence Reference Kessler RC, et al. Psychological Med. 2002; 32: 1213–1225. Substance use disorders Patients† with GAD reporting other lifetime disorder (%) *The lifetime prevalence was defined as the proportion of individuals who have manifested GAD at least once in their lifetime. †Subset of population with GAD (based on surveys in four countries). Kessler RC, et al. Psychological Med. 2002; 32: 1213–1225. LYG100 January 2009 4

GAD often precedes the development of other psychiatric disorders Anxiety disorders Mood disorders In an analysis of surveys from four countries (Brazil, Canada, the Netherlands and the United States) including over 20,000 individuals aged 18 years, the pattern of comorbidity in patients with GAD was determined The Composite International Diagnostic Interview administered by a lay interviewer was used to assess DSM-III-R anxiety, mood and substance use disorders in these surveys The combined total lifetime prevalence estimates of GAD across all four countries was 3.9% Of the individuals with GAD, 88.3% reported suffering from any comorbid disorder (agoraphobia, panic disorder, simple phobia, social phobia), mood disorders (dysthymia, major depression, mania) or substance use disorders (substance abuse or dependence) Of the 58% patients with GAD who reported a history of another anxiety disorder, GAD preceded the development of that anxiety disorder in 25.3% Of the 71.6% of those with GAD who reported a history of mood disorders, GAD preceded the mood disorder in 28.7% of patients Reference Kessler RC, et al. Psychological Med. 2002; 32: 1213–1225. Substance use disorders Patients* in whom GAD precedes comorbid condition (%) *Subset of population with GAD (based on surveys in four countries). Kessler RC, et al. Psychological Med. 2002; 32: 1213–1225. LYG100 January 2009 5

GAD is associated with increased primary and secondary care visits Referrals by GP GP visits Number of visits Number of referrals ** 67% 39% A retrospective longitudinal analysis of the General Practice (GP) database in Germany evaluating some of the clinical and economic characteristics of patients with GAD The database included information for ~900 practices and had 4.2 million patient records Included in the analysis were GAD patients older than 18 years who had had at least one visit to the GP for GAD in the past year An age- and gender-match comparison group was randomly selected from the database These patients had no GP visits or prescriptions for anxiety or depression Information on demographics, concurrent conditions, medication use, doctor visits and referrals was derived from the database. In total, 3340 GAD patients and 3340 in the comparison group were included in the analysis (66% women, mean age 53 years) This slide shows the distribution of GP visits and the number of referrals to other medical practitioners Patients with GAD had substantially more GP visits than the matched comparison group. 60% of GAD patients had more than six GP visits in the year compared with 25% in the comparison group. The mean number of GP visits in the year was nine for GAD patients and 6 for the comparison group (p<0.01) Two-thirds of patients with GAD were referred to other medical practitioners in the year compared with 39% in the comparison group. The mean number of referrals was three for GAD and two for the comparison group (p<0.01) These data indicate that patients with GAD incur a substantial use of healthcare resources Reference IMS Mediplus Database German GP Analysis. Data on file, Pfizer Ltd PGB026: GAD German GP Database. Manuscript by Berger et al. Submitted. **p<0.001 vs comparison group GAD in German GP database N=3340 in each group. Frequency in the year IMS Mediplus Database German GP Analysis. Data on file, Pfizer Ltd PGB026: GAD German GP Database. LYG100 January 2009 6

Patients with GAD Are high users of emergency services At a high risk of suicide attempts Are at risk of substance misuse

Patients with GAD report greater work impairment than patients with MDD The German National Health Interview and Examination Survey, Mental Health Supplement was a community-based study of both somatic/physical and mental health, and involved a representative sample of 4181 individuals between the ages of 18 and 65 years The Composite International Diagnostic Interview was applied by clinically trained interviewers to diagnose DSM-IV psychiatric disorders. As part of the survey, participants were asked how many days in the past 4 weeks they were completely unable to work or to carry out normal everyday activities, and how many days in the past 4 weeks they were limited in their ability to carry out normal activities because of their syndrome Only 0.2% of respondents who did not have GAD or major depressive disorder (MDD) reported 3 days lost in the past month, and only 1.9% of those reported 6 days impaired in the past month Of the respondents with pure GAD, 10.9% reported 3 days lost, and 34.3% reported 6 days impaired in the past month The proportion of individuals with GAD who had work loss/impairment was greater than that observed in those with pure MDD Individuals with both GAD and MDD were associated with the greatest work impairment/loss Reference Wittchen H, et al. Int Clin Psychopharmacol. 2000; 15: 319–328. This study is based on data from the German National Health Interview & Examination Survey. *95% confidence intervals. MDD, major depressive disorder. Wittchen HU, et al. Int Clin Psychopharmacol. 2000; 15: 319–328. LYG100 January 2009 8

Improving detection and diagnosis of GAD Become familiar with symptoms and Signs of GAD Assess level of disability to decide on threshold for RX Ask about long standing anxiety symptoms when patients present with depression and or unexplained physical symptoms

Scales for Dx. Anxiety D/O HAM-A BAI HADS

GAD-7 for scoring symptom severity in GAD Cut points of 5, 10 and 15 represent mild, moderate and severe anxiety Spitzer RL et al. Arch Intern Med 2006; 166: 10-17