1. AFFECTIVE DISORDERS LONG-TERM TREATMENT OF DEPRESSION PROF. MUDr. JIŘÍ RABOCH 1.LF UK A VFN PRAHA

2. AFFECTIVE DISORDERS in the history 4. b.c. Hippokrates - melancholy, mania 1899 Kraepelin manic depressiv psychosis 1953 Kleist, Leonhard - unipolar x bipolar depression

3. Paradigms of depression and its treatment

4. THE GLOBAL BURDEN OF DISEASE Ch.J.L.MURRAY, A.D.LOPEZ, 1997 HARVARD SCHOOL OF PUBLIC HEALTH WORLD HEALTH ORGANISATION WORLD BANK

5. DALY - Disability Adjusted Life Years DALY = YLL + YLD YLL - Years of Life Lost YLD - Years Lived with Disability

6. % DALY OF NEUROPSYCHIATRIC DISORDERS IN VARIOUS PARTS OF THE WORLD Disability Adjusted Life Years Murray a Lopez, 1997

7. 10 MAIN CAUSES OF DEATH established market economies Years of Life Lost Murray a Lopez, 1997

8. 10 MAIN CAUSES OF DISABILITIES established market economies Murray a Lopez, 1997 Years Lived with Disability

9. DALY (%) world 1.Respiratory infections8,2 2.Diarhoea7,2 3.Perinatal conditions6,7 4.Major depression3,7 5.IHD3,4 6.CVD2,8 7.Tuberculosis2,8 8.Measles2,7 9.Traffic accidents2,5 10.Congenital anomalies2,4 Murray a Lopez, 1997

10. DALY (%) established market economies 1.9,9 2.Major depression6,1 3.CVD5,9 4.Traffic accidents4,4 5.Alcohol use4,0 6.Osteoarthritis2,9 7.Trachea, bronchus, lung cancers2,9 8.Dementias2,7 9.Self-inflicted injuries2,3 10.Congenital anomalies2,2 Murray a Lopez, 1997

11. DALY (%) established market economies age 15 - 44 1.Major depression12,3 2.Alcohol use8,9 3.Traffic accidents8,5 4.Schizophrenia5,0 5.Self-inflicted injuries4,2 6.Bipolar disorder3,7 7.Drug use2,9 8.OCD2,7 9.Osteoarthritis2,7 10.Violence2,4 Murray a Lopez, 1997

12. DALY formerly socialist countries Murray a Lopez, 1997

13. LIFE-TIME PREVALENCE (%) NCS TOTALMenWomen Affective disorders 17,112,721,7 Anxiety disorders 24,919,230,5 Dependencies26,635,417,9 Non-affektive psychoses 0,70,60,8 Mental disorders 48,048,747,3 Kessler, 1994

14. Cumulative frequency of depression according to the decade of birth and the age at the start of the disease ECA study 1955+ 1945-1954 1935-1944 1925-1934 1915-1924 1905-1914  1905 Wittchen et al., 1994

15. FIRST OUT-PATIENT PSYCHIATRIC EVALUATION DURING A YEAR (2 450 106 EVALUATIONS) DIAGNOSIS19942003CHANGES (%) ORGANIC DISORDERS27 42145 08364,4 DEPENDENCIES31 09734 48410,9 SCHIZOPHRENIA33 80537 98712,4 AFFECTIVE DISORDERS37 91579 215108,9 NEUROTIC DISORDERS103 577158 16852,7 CHILDRENS MENTAL DISORDERS 23 46021 162-9,8 TOTAL307 877419 17536,2 ÚZIS 2005

16. CUMULATIVE FREQUENCY OF RELAPSES OF DEPRESSION (378 patients with depressive disorder) years Cumlative frequency (%) Rothschild, A. J., 1999)

17. LONG-TERM COURSE OF DEPRESSION 2/3 suicidal ideas 7 – 15 % commits suicide Keller a Sadock, 1991

18. NUMBER OF COMMITED SUICIDES/100 000 WHO 2000

19. COMITTED SUICIDES CZECH REPUBLIC /100 000 ÚZIS 2003

20. CZECH REPUBLIC 2002 - COMMITED SUICIDES 1483 (1 173 men a 310 women) ÚZIS 2003

21. FACTORS INFLUENCING THE COURSE OF DEPRESSION GENETIC RISK AGE AT THE START OF DEPRESSION (<25, 60<) NUMBER OF PREVIOUS EPIZODES AND THEIR LENGTH REZIDUAL SYMPTOMS COMORBIDITY FEMALE GENDER PSYCHOSOCIAL SITUATION (PARTNER) BIOLOGICAL FACTORS – SLEEP PATTERN, HHA ACTIVITY

22. PHASES OF DEPRESSION TREATMENT (Kupfer, 1991) time Depression intensity acute continuing maintenance

23. DEPRESSION TREATMENT OPTIONS ANTIDEPRESSANTS, OTHER DRUGS PSYCHOTHERAPY (KBT, IPT) OTHER BIOLOGICAL METHODS ECT rTMS PHOTOTHERAPY SLEEP DEPRIVATION VNS, DBS

24. PHASES OF DEPRESSION TREATMENT (Kupfer, 1991) time Depression intensity acute continuing maintenance

25. FINISHING THE CONTINUING TREATMENT PHASE 4 – 9 MONTHS OF EUTHYMIA NOT FULFILLING THE CRITERIA FOR MAINTENANCE TREATMENT THE PATIENT IS ASKING FOR DISCONTINUATION SYNDROM – TCA, SSRI WITH SHORT-TERM ELIMINATION HALF-TIME SLOWLY DECREASING THE DAILY DOSAGE - 25 % DD PER MONTH

26. PHASES OF DEPRESSION TREATMENT (Kupfer, 1991) time Depression intensity acute continuing maintenance

27. MAINTENANCE THERAPY Maixner a Greden, 1998

28. MAINTENANCE TREATMENT (LONG-TERM) WHAT ANTIDEPRESSANT WHAT DOSAGE HOW LONG

29. WHAT ANTIDEPRESSANT?

30. MAINTENANCE TREATMENT (LONG-TERM) LITHIUM CLASSICAL ANTIDEPRESSANTS IMAO, RIMA SSRI OTHER MODERN ANTIDEPRESSANTS

31. RESUTLTS OF MAINTENANCE TREATMENT WITH IMIPRAMINE IN 4. AND 5. YEARS IN COMPARISON WITH PLACEBO ( Kupfer, D.J., et al., 1992) p<0,006 Imipramin (n=11) Placebo (n=9) Cumulative frequency of patients in remission i

32. SSRIs – inhibition of P450 microsomal enzymes ( Edwards, J.G. a Anderson, I., 1999

33. POTENTIALLY SERIOUS DRUG INTERACTIONS OF SSRIs

34. MAINTENANCE DEPRESSION TREATMENT SSRIs > CLASSICAL ANTIDEPRESSANTS SIMILAR EFFECT BETTER TOLERABILITY COMORBID DISORDERS ONCE A DAY DOSAGE LOW INTOXICATION LETHALITY ANDERSON, 1998

35. HOW LONG?

36. Recurrences in 105 patients with major depression after 5 years-remission (Mueller, T.I., et al., 1999)

37. WHAT DOSAGE?

38. DOSAGES OF ANTIDEPRESSANTS IN MAINTENANCE TREATMENT OF DEPRESSION IMIPRAMINE – 3-YEARS FOLLOW-UP – 100 mg - 70 % RELAPSES 200 mg - 30 % RELAPSES (FRANK et al., 1993) CITALOPRAM 20 i 40 mg EFFECTIVE IN CONTINUING TREATMENT (MONTGOMERY et al., 1993) DECREASING THE DOSAGE OF CITALOPRAM FROM 40 TO 20 mg 2-YEARS FOLLOW-UP – 50 % RELAPSES (FRANCINI et al.,1999)

39. COMPLIANCE STRATEGIES FOR IMPROVING PATIENT – PHYSICIAN RELATIONSHIP EDUCATION ADEQUATE FARMAKOTHERAPY Haddad, 2000

40. PSYCHOFARMACOLOGICAL THERAPY ONLY 13,4 % OF PEOPLE WITH DEPRESSIVE SYMPTOMS (!!!) Vaněk, Raboch, Vaněk, 2000