Viewpoint of Western Europe on Treatment of Depression

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Viewpoint of Western Europe on Treatment of
Depression

• Professeur Hervé ALLAIN
• University of Rennes I
• Rennes - FRANCE

Moscow, Russia October 11th, 2000
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Epidemiologic Data(Epidemiologic Catchment Area
Study)

• 1800 patients
• bi-polar disorders 1.2
• dysthymic disorders 3.1
• major depression 4.4
• Prevalence in Europe 10
• Incidence
• Prevalence peak 25-44 yrs
• before 35 in women, after 55 in men

Twice more in women
4.3
7.6
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Risks Associated with Depression it is a severe
disorder

• 1. Risk of suicide
• 2. Alteration of social and professional behavior
• 3. Pain felt by the patient
• 4. Recurrences, relapses
• 5. Comorbidity
• Alcoholism, drugs, anxiety, social isolation
• 6. Chronicity / suicide attempts

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Suicide in the Youngest ( /100,000)
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Biologic Theories of Depression

• 1. Aminergic theory
• ? of aminergic neurotransmitters
• selective ? of serotonin
• 2. Renewal of GABA
• see I Shin-Shiad and L.N. Yathan
• Life Sciences 1998 63 1289-1303

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Biologic Theories of Depression

• 3. Other approaches
• Substance P. Interleukin (cytokines)
• Dysregulation of genic control
• Role of deep brain stimulation

PRESENTLY AVAILABLE ANTIDEPRESSANTS AMINES , 5
HT, MAOI-A
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Serotoninergic Theory of Depression

• Psychologic disorders associated with an
  alteration of the serotoninergic system
• Could explain the patient s dark mood
• Tryptophan improves mood
• serotonin (5 HT) is antidepressant

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Effect on the Serotoninergic Receptors

• Stimulation of 5HT1
• Antidepressant and Anxiolytic effects
• Stimulation of 5HT2
• agitation, nervousness, sleep disturbance,
  sexual dysfunction
• antidepressant activity ?
• Stimulation of 5HT3
• nausea, vomiting, headache

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History of antidepressant drugs

• A discovery
• Tricyclic antidepressants (1957)
• MAOI
• Selectivity
• SSRIs (1987)
• Return to multiple impacts
• NaSSA

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The Ideal Antidepressant

• Efficacy
• on mood
• rapidly effective
• Safety
• good acceptability
• no dependency
• no tolerance
• Choice?

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EVOLUTION OF DEPRESSION UNDER TREATMENT
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Relationship between antidepressants and
neurotransmission
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Comparative Side Effects of Commonly used
antidepressants
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Fluvoxamine - FEVARINE(Tradename in France
Floxyfral)

• Presentation tablets 25, 50 and 100 mg
• Initial dose 50 mg/day
• Maintenance Dose 100 - 300 mg/day

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FLUVOXAMINE

• 1. Very selective for 5-HT recapture so few
  side-effects
• 2. Less toxic than tricyclics in case of
  poisoning
• 3. Few drug interactions (5-HT-syndrom)
• 4. One drug intake a day (good compliance)
• 5. Same dosage for elderly
• 6. Efficacity and safety largely proven WARE
  MR, J Clin Psychiatry 1997 58 suppl 5
  15-23 MARTIN AJ, WAKELIN J, Br J Clin Pract
  1986 40 95-99 MACKAY FJ, Pharmacology and
  Drug Safety 1997 6 235-246

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Prescriptions of Antidepressants in 3 European
Countries (1997)
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Course of Depression in Europe

• The antidepressants, presently used, are
  EFFECTIVE
• 70 of patients are improved
• Placebo effect 40
• Ambulatory treatment or hospitalization

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Reasons for Consultation with or Referal to
Psychiatrist

BMJ 1999 318 1188-91

• Uncertainty about diagnosis
• Severe depression, in particular with psychotic
  features or suicide risk
• Bipolar disorder
• Coexistence of other psychiatric disorders such
  as alcoholism or severe personality disorder
• Failure to respond to treatment
• Intolerance of adverse effects

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Drug treatment of depression summary points
BMJ 1999 318 1188-91

• Outcome can be significantly improved
• by non-pharmacological factors,
• such as good therapeutic alliance between the
  doctor and the patient
• A practical approach is to prefer
• newer antidepressants in mildly and moderately
  depressed patients
• tricyclic antidepressants or venlafaxine in
  severely depressed patients

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Drug treatment of depression summary points
BMJ 1999 318 1188-91

• Antidepressants take 1-4 weeks before an effect
  is evident
• this delay may be longer in elderly people
• If patients do not respond,
• check compliance and reconsider the diagnosis
• before changing or adding drugs

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Drug treatment of depression summary points
BMJ 1999 318 1188-91

• After the initial treatment response,
• the drug shoud be continued at the same dose for
  at least 4-6 months
• The dose should be gradually lowered
• over several weeks before withdrawal

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Antidepressants
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Conclusion

• Depression is ONE OF THE MAJOR PROBLEMS in
  western European countries
• It concerns ALL AGES including children, elderly
  subjects
• It requires a RAPID DIAGNOSIS and an URGENT
  TREATMENT
• Today treatment during 6 months
• SSRIS ARE THE INITIAL TREATMENT OF CHOICE

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Conclusion
GOOD TOLERANCE OF THE PRODUCTS PROVEN EFFICACY

• ? OF SLEEP DISTURBANCE AND SUICIDE
• IMPROVED PUBLIC HEALTH

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www.med.univ-rennes1.fr/etud/pharmaco
www.biotrial.com Herve.Allain_at_univ-rennes1.fr