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

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

Paradigms of depression and its treatment

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

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

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

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

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

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

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

DALY (%) established market economies age 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

DALY formerly socialist countries Murray a Lopez, 1997

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

Cumulative frequency of depression according to the decade of birth and the age at the start of the disease ECA study  1905 Wittchen et al., 1994

FIRST OUT-PATIENT PSYCHIATRIC EVALUATION DURING A YEAR ( EVALUATIONS) DIAGNOSIS CHANGES (%) ORGANIC DISORDERS ,4 DEPENDENCIES ,9 SCHIZOPHRENIA ,4 AFFECTIVE DISORDERS ,9 NEUROTIC DISORDERS ,7 CHILDRENS MENTAL DISORDERS ,8 TOTAL ,2 ÚZIS 2005

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

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

NUMBER OF COMMITED SUICIDES/ WHO 2000

COMITTED SUICIDES CZECH REPUBLIC / ÚZIS 2003

CZECH REPUBLIC COMMITED SUICIDES 1483 (1 173 men a 310 women) ÚZIS 2003

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

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

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

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

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

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

MAINTENANCE THERAPY Maixner a Greden, 1998

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

WHAT ANTIDEPRESSANT?

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

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

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

POTENTIALLY SERIOUS DRUG INTERACTIONS OF SSRIs

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

HOW LONG?

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

WHAT DOSAGE?

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)

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

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