1. MAnagement of biPolar disease in INtercontinental reGion: MAPING Preliminary results P.M Llorca, M.M Jalal Uddin, S.A Ahmadi Abhari, F Nacef, V Mishyiev, D Aizenberg, L Melas-melt, I Sedeki

2. Disclosures P-M Llorca – Advisory board: Astra-Zeneca, Janssen, Lilly, Lundbeck, Otsuka, Roche, Takeda – Involvement in clinical trials for: Amgen, Astra-Zeneca, Lundbeck, Roche, Sunovion – Educational grants for research, honoraria and travel support for activities as a consultant/advisor and lecturer/faculty member for pharmaceutical companies: Astra-Zeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Lundbeck, Otsuka, Roche, Sanofi, Servier MaPing Study was funded by Sanofi

3. Rationale of the study / selection of patients MAPING study aims to provide information on the management of patients with BD in everyday practice, across 6 different countries (Bangladesh, Egypt, Iran, Israel, Tunisia and Ukraine) International, multicenter, non-interventional, cross- sectional registry in bipolar patients Selection of physicians – 90 sites were randomly selected from a pre- established list from Bangladesh, Egypt, Iran, Israel, Tunisia and Ukraine (in psychiatric hospitals, general hospitals or community). Selection of patients – Clinicians at each site screened all their consecutive eligible patients (BD, DSM-IV criteria), during a period of 8 months.

4. Main variables collected Patient’s characteristics: – age – sex – educational level – professional status – degree of disability – alcohol and other substance abuse – medical history – associated psychiatric diseases – family history of psychiatric diseases Pharmacological treatment used: – ongoing or prescribed Psychiatric hospitalizations during the last 12 months Disease characteristics: – time from first diagnosis – nature of first diagnosis – time from start of Bipolar Disorder – type of Bipolar Disorder – episodes during the last 12 months – presence of psychotic symptoms – characteristics of mood disorders – social, familial and occupational dysfunction during the last two months

6. Results Physicians’ characteristics : -85 psychiatrists -Mean age 50.6 ± 8.2 years (21.4 ± 8.3 years of practice). -Male 77.5% -Median number of BP seen per month : 90 -International guidelines used : -very frequently: 49.4% -from time to time: 48.3%

7. Description of the studied population Socio-demographic aspects Mean age : 37.9 ± 13.2 years 52.8% male - 47.2% female 47.6% married (n=562) Living in an urban area: 69.3%(n=818) 79.6% of patients had a secondary or higher level of education 53.4% of patients were unemployed (n=630) For 47.0% (n=296) unemployment was due to a work disability. 13.6% of patients (n=161) were in part-time employment due to their bipolar disorder. For patients in full-time or part-time employment: – 54.8% of patients had taken sick leave during the past 12 months, with a median duration of 35 days (range: 2- 365)

8. Description of the studied population Disease characteristics 72.2% were diagnosed as BP I 25.7% were diagnosed as BP II Median time from initial diagnosis was 80 months (range: 0 – 608) 64.4% of patients were diagnosed before the age of 30 Predominant initial diagnoses: – ‘Major depressive disorder’ 36.4% – ‘Other: bipolar disorder’ : 20.1% 80.8% of patients experienced 1 to 3 episodes in the last 12 months (predominant polarity of episodes ‘Maniac’ : 65.9%)

9. Description of the studied population History of treatments 44.4% of patients received antidepressants at initial diagnosis (SSRIs: 67.2%) 29.7 % of patients received anticonvulsants at initial diagnosis 67.2% of patients received antipsychotic drugs at initial diagnosis – first generation drugs: 51.1% – second generation drugs: 51.6% (‘Major depressive disorder’ and ‘Other: bipolar disorder’ were the predominant initial diagnoses : 36.4% and 20.1% respectively) 30 % of patients received anxiolytics at initial diagnosis From the 63.8% patients who received a previous antidepressant: – 46.1% experienced manic or hypomanic switches – 30.3% experienced irritability – 29.6% experienced mood lability

10. Description of the studied population Current symptoms 69.9% of patients presented at least one current symptom of mania The most frequent current symptoms of mania reported were: – ‘Feeling unusually ‘high’ and optimistic or extremely irritable’ : 52.7% of patients – ‘Sleeping very little, but feeling extremely energetic’: 50.8% of patients 45.0% reported current symptoms of bipolar depression The most frequently reported were: – ‘Sleep problems’: 30.9% of patients – ‘Feeling hopeless, sad, or empty’: 28.2% of patients – ‘Fatigue or loss of energy’: 26.8% of patients – ‘Concentration and memory problems’: 26.3% of patients

11. Description of the studied population Functioning Global assessment of functioning during the last two months (GAF): – Social, familial and occupational dysfunction during the last 2 months was moderate with a mean score of 54.7 ± 19.7.

12. Functional consequences of the disease Relation to symptoms Functioning (GAF score) was statistically significantly worse when: – Current manic symptoms were experienced: 51.0 ± 19.0 versus 56.0 ± 18.9 for depression symptoms (p<0.001) – Patients with a symptom of mania had a more negative perception of social functioning than patients without mania Symptoms of depression were not correlated with the GAF score except for ‘Thoughts of death or suicide’ (50. 0± 20.0 versus 55.3 ± 19.6, p=0.005)

13. Functional consequences of the disease Symptoms The total number of current symptoms (either mania or depression) was significantly negatively correlated to the GAF Score The more symptoms experienced by the patients the lower the GAF score

14. Functional consequences of the disease Time before diagnosis and episodes Time between initial diagnosis and bipolar disorder diagnosis was poorly correlated with GAF score (Spearman correlation coefficient of 0.055, p = 0.060): Median times were longer in patients with a high GAF score (1.5 years and 2.8 years for patients with median GAF score 81-90 and 91-100, respectively) than in patients with low GAF score (0.6 year and 0.9 year for patients with median GAF score 1-10 and 11-20, respectively). Functioning (GAF score) was statistically significantly worse when: – the number of episodes that occurred in the last 12 months was higher than or equal to 4 (46.1 ± 19.0 versus 55.3 ± 19.6, p<0.001) – at least one psychiatric hospitalization occurred in the last 12 months (59.6 ± 18.7 versus 49.3 ± 19.5 for one hospitalization and 47.8 ±18.9 for multiple hospitalizations p<0.001)

15. Functional consequences of the disease Important impact of manic symptoms Impact of suicidality Impact of the number of symptoms Impact of the number of episodes

16. Current symptoms and current treatment Symptoms of mania were associated with: – a statistically significant increase in antipsychotic drug prescription (e.g. from 78.7% to 91.2% for ‘unrealistic, or grandiose beliefs about one’s abilities or powers’) – Patients who reported ‘Racing thoughts: jumping quickly from one idea to the next’, ‘Sleeping very little, but feeling extremely energetic’ or ‘Impaired judgment and impulsiveness’ received more mood stabilizers than others (respectively 90.0% versus 83.2%, 88.6% versus 82.6% and 88.1% versus 83.9%) – a decrease in antidepressant drug prescription (from 44.6% to 21.9%) Depression symptoms were associated with – a significant increase in antidepressant drug prescription (e.g. from 21.5% to 73.3% for ‘hopelessness, sadness or emptiness feelings’) – a decrease in antipsychotic drug prescription (apart from ‘Feelings of worthlessness or guilt’, ‘Thoughts of death or suicide’ and ‘Irritability’)

17. Curent symptoms and history of treatment Symptoms of mania were significantly less present in patients that took antidepressant at least once in lifetime: – e.g. from 71.6% to 50.8% for ‘unrealistic, or grandiose beliefs about one’s abilities or powers’ Bipolar depression symptoms were significantly more present in patients that took antidepressant at least once in lifetime: – from 55.5% to 85.0% in case of hopelessness, sadness or emptiness feelings for instance

18. Current symptoms and treatment Antidepressants are largely used for bipolar depression in our sample Second Generation Antipsychotics and Mood stabilizers are the most prescribed for manic symptoms – The difference of use between those two classes remains difficult to describe

19. BP I vs BP II Time between initial diagnosis and bipolar disorder # P-value, Wilcoxon-Mann-Whitney test (Two-sided). * P-value, Chi-square test The average time from initial diagnosis to bipolar disorder diagnosis was shorter for BP I patients (median time of 0.8 year) than for BP II (median time of 2.2 years)

20. BP I vs BP II Functioning BP I patients had a lower GAF score than BP II patients: 53.8 ± 20.0 versus 56.9 ± 18.5 (p = 0.017): – BP I patients suffered from more social, familial and occupational dysfunction in the last two months Work status and productivity: – no statistically difference between BP I and BP II. Work productivity by bipolar disorder type

21. BP I vs BP II Treatments BP II patients tended to receive more antidepressants than BP I patients: 58.1% versus 27.8% – SSRIs remained the most common antidepressant for BP II (80.1%) and BDI (76.4%) BP I patients tended to receive more antipsychotics (87.7%) than BP II patients (72.3%) – Second generation antipsychotic were received by more patients suffering from BDII than BDI (91.8% versus 75.9%). BP I patients tended to receive more anxiolytics (54.8%) than BP II patients (41.3%) – Benzodiazepines were the most commonly used anxiolytic for both bipolar disorders (98.6% for BDII and 96.8% for BDI)

22. BP I vs BP II BP II is less recognized compared to BP I BP I have more important functional consequences in all the domains BP II received more AD (SSRIs) and more SGA