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Ten Leading Causes of DALYs in 2020
(Disability Adjusted for Life Years)
In the World
Both sexes Disease or injury
Males Disease or injury
Females Disease or injury
All causes All causes All causes
1-Ischaemic heart disease
Ischaemic heart disease
Unipolar major depression
2-Unipolar major depression
Road traffic accidents
Ischaemic heart disease
3-Road traffic accidents
Cerebravascular disease
Cerebravascular disease
4-Cerebravascular disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
5-Chronic obstructive pulmonary disease
Unipolar major depression
Road traffic accidents
Ustun et al (2004) Brit. J. Psychiat.
Prevalence of depression
WHO - Fact Sheet N° 265, December 2001
Copeland et al (1987); Gräsbeck (1996); Hagnell et al (1982)
9.5% of
women
5.8% of men
10-15% of elderly 65
years
15
“ICEBERG” PHENOMENON”
Depressed patients
seen by psychiatrists
Depressed patients seen in
primary care practice
Treatment of depression
Tylee A et al, Int Clin Psychopharmacol,1999,14(3):139–51;Lépine, JP et al.,
Int Clin Psychopharmacol, 1997,12:19–29.
- Do not seek help
- Undiagnosed
- Diagnosed but untreated
- Treated but non compliant*
Receive antidepressant
(4.4%)
Adequately treated
(?%)
Untreated patients
(95.6%)
Depressed Patients
(100%)
The hidden cost of not treating Mood
Disorders
Dysfunctional families
Absenteeism
Decreased productivity
Job-related injuries
Adverse effect on quality control in the workplace
Key symptoms
Emotional Physical
Sad mood
Loss of interest or pleasure
Feelings of worthlessness or
excessive guilt
Thoughts of death, suicide
Diminished ability to think or
concentrate
Psychomotor retardation or
agitation
Sleep disturbances
Weight loss or weight gain
Fatigue or loss of energy
American Psychiatric Association (1994)Other key symptoms
Don‟t chase symptoms –
treat the core
Tachycardia/irregular heart beat
Presenting complaint
Cardiological
Chest pain
Neurological
Headache
Dizziness
Syncope/seizures
Gastrointestinal
Epigastric pain
Diarrhoea
„Asthma‟
Pulmonary
Dyspnoea
0 10 20 30 40 50 60
% patients
Wayne Katon (1984)* DSM-IV-TR™ 2000
Medical Condition Frequency of Major Depression
Coronary Artery Disease 30-60%
Emphysema 20-40%
HIV infection 20-35%
Hypothyroidism 10-30%
Stroke 10-25%
Diabetes Mellitus 10-20%
Renal Failure 5-20%
Kaplan HI, 1994
The association between depression
and medical illness
What are we trying to achieve for
our depressed patients?
To return them to „health‟
“Health is a state of complete physical, mental and
social well-being and not merely the absence of
disease or infirmity”
World Health Organisation
Preskorn SM. J Clin Psychiatry 1997;58 (suppl 6):3-8.
S
T
E
P
S
STEPS: Factors to Consider in
Antidepressant Selection
Safety
Drug-drug interaction potential
Tolerability
Acute and long term
Efficacy
Onset of action
Treatment and prophylaxis
Payment
Cost effective
Simplicity
Dosing
Need for monitoring
73
Comparison of SSRI and Benzodiazepine
Drugs
SSRI BZ
Broad spectrum Yes No
Rapid onset No Yes
Tolerability Fair Good
CYP 460 interactions Yes No
Discontinuation sx Yes Yes
Abuse potential No Yes
Early activation Yes No
SSRIs/SNRIs bind only to the
primary site
The net result is
an intermittent
blockade of the
serotonin transporter
protein
Cipralex binds both to the primary
and the allosteric site
The net result is
Stronger and longer
binding to the serotonin
transporter protein
1. Von Moltke et al. Drug Metab Dispos 2001;29:1102-9
2. Greenblatt et al. J Clin Psychiatry 1998;59:19-27
3. Albers et al. Psychiatry Res 2000;96:235-243
Low potential for drug-drug
interactions
3A4 2D6 1A2 2C19 2C9
Escitalopram1 0 + 0 0 0
Citalopram2 0 + + 0 0
Fluoxetine2 ++ +++ + ++ ++
Paroxetine2 + +++ + + +
Venlafaxine3 + + 0 0 0
Fluvoxamine2 ++ + +++ +++ ++
Sertraline2 + + + ++ +0 = Negligible
+ = Very weak interaction
Cytochrome P450 Isozyme Inhibition In Vitro/In Vivo
++ = Moderate interaction
+++ = Strong interaction
•Ca+ antagonists
•Erythromycin
•Ketoconazole
•Lidocaine
•Cancer therapies
•Anti-Arrhythmic
•B-blockers
•Haloperidol
•Neuroleptics
•Caffeine
•Ciprofloxacin
•Theophylline
•Verapamil
•Diazepam
•Propranolol
•Moclobemide
•Imipramine
•Miconazole
•Phenytoin
•S-warfarin
•NSAIDs
Cipralex® is the true SRI
SRI
NRI
Fluoxetine1
SRIFluvoxamine1
DRI
SRISertraline1
SRICipralex3
SRI
NRI
Paroxetine1
DRI
SRIVenlafaxine2
Stahl SM. Using secondary binding properties to select a not so selective reuptake inhibitor. J Clin. Psychiatry 1998;59:642n3
Conclusions :
• Cipralex is an extremely selective serotonin reuptake
inhibitor .
• Cipralex has no effect on 140 receptors , Enzymes or
Ion channels .