1. Professor of Pharmacology
Antidepressant Drugs By
Dr. Yieldez Bassiouni
Professor of Pharmacology

2. What is Depression ?
It is one of the most common psychiatric disorder, characterized by intense feeling of sadness, hopelessness , and despair and inability to experience ordinary pressure to cope with ordinary life events

3. When depression is neglected or severe it can lead to:
Complications
When depression is neglected or severe it can lead to:
-Suicide Substance abuse
-Alcoholism Heart problems
-Work-related problems -Family conflicts
-Social isolation

4. Old classification of depression
Unipolar depression
is more common and affects old patients who are
subjected to certain circumstances associated with
Anxiety. Mood remains at one emotional state or pole".[
Patients are usually inert
Bipolar depression
develops early in life and a hereditary factor may
be involved, and patients oscillate between
depression and mania

5. Postpartum depression
Types of depression
Major Depression
(Unipolar)
Dysthymia
low mood almost daily
Delusions,hallucinations
Psychotic Depression
Manic Depression
(Bipolar)
Atypical Depression
(w gain, sleep)
Postpartum depression

6. Factors affecting depression
Several risk factors appear to work together
to cause or precipitate depressive disorders,
the most important of these are:
Genetic influences
Environmental
Biological factors

7. Genetic influences
Some types of depressions like bipolar and the early onset depression (before the age of 25) are thought to be genetically determined disorders. Identical twin studies revealed that if one of them suffers from depression or manic-depressive disorder, the other twin has a 70 % chance of having the illness

8. Environmental 1) Early childhood trauma or abuse
2) Loneliness and lack of social support
3) Recent stressful or traumatic life
experiences
4) Alcohol and drugs
5) Finances and employment
6) Health problems or chronic pain

9. Biological factors
Imbalances of neurotransmitters ; mainly serotonin (5-HT) and norepinephrine (NE) play a major role in pathogenesis of depression

10. 5-HT deficiency may cause the sleep problems,
irritability, and anxiety associated with depression
Decreased level of NE, which regulates mood,
alertness, arousal, appetite, reward & drives, may
contribute to the fatigue and depressed
mood of the illness
اليقظة والإثارة، وشهية
However, dopamine (D) is important for pleasure,
sex & psychomotor activity

11. Theories of Depression
The etiology of depression is too complex
to be totally explained by a single theory
1. Neurotrophic hypothesis
2. The monoamine theory
3. The dysregulation hypothesis
4. Neuro-endocrinal hypothesis

12. Electroconvulsive therapy (ECT)
Therapies for depression
Pharmacotherapy
Psychotherapy
Electroconvulsive therapy (ECT)

13. Electroconvulsive therapy

14. Indications
ECT can be life-saving & produce dramatic relief for: -Pregnant patients -Patients intending suicide -Intractable mania -Some cases of psychotic depressions -People who cannot take antidepressants due to problems of health or compliance

15. combination of pharmacotherapy & psychotherapy may improve the treatment response, enhance the quality of life
Psychotherapy

16. Pharmacotherapy

17. Monoamine nerves: Neurotransmission

18. Sites of Action for Antidepressants
1- Monoamine (NE or/ and 5-HT) re-uptake pump inhibitors
2- Blockade of pre-synaptic a2 receptors
3- Inhibition of MAO enzyme

19. Classification of Antidepressant Drugs
Tricyclic Antidepressants
Mixed - action Novel Drugs
Selective Serotonin Reuptake Inhibitors
MAO Inhibitors

20. Tricyclic antidepressants
# TCAs are the oldest class of antidepressant drugs
# They have characteristic three-ring nucleus
# Older agents ‘first generation’ TCAs; Imipramine – Amitriptyline are the prototypical drugs of the class as mixed NE & 5-HT reuptake
inhibitors
# They can be used for long duration for Rx of depression without loss of effectiveness

21.   Mechanism of Action
TCAs inhibit the neuronal reuptake of NE and 5HT into presynaptic nerve terminals leading to an increased concentration of these monoamines in the synaptic cleft in the brain N.B. Like phenothiazines, TCAs block adrenergic (α1), histamine (H1)and muscarinic (M1)receptors

24. Classification of TCAs
Tertiary amines
-Block the reuptake of
5-HT& NE
- more side effects
1- Imipramine
2- Amitriptyline
Secondary amines
- More selective to NE
-less side effects
1- Desipramine
2- Nortriptyline
Tetracyclic antidepressents
Maprotiline: has a strong H1 blocking activity = sedative effect

25. TCAs: Secondary vs Tertiary Amines

26. Pharmacological actions
1- Elevate mood
2- Improve mental alertness
3- Increase physical activity
# The antidepressant effect may develop after several weeks of continued treatment ( weeks)
4- In non-depressed patients They cause sedation, confusion & motor incoordination

27. Clinical indications 1- Treatment of major depression &
panic disorders
2- Depressed phase of bipolar
depression with mood stabilizer
3- Obsessive-compulsive disorders
4- Together with antipsychotics in
Rx of depressed psychotic patients
5-Treatment of resistant depression that
has failed to respond to standard
SSRI therapy

28. Clinical indications 5- Imipramine used to control
bed-wetting in children
(nocturnal enuresis)
by causing contraction of
’ internal sphincter of ’ bladder
6- Analgesia in neuropathic pain
chronic painful states
(They modulate opioid
systems in the CNS)

29. Adverse Effects 1- Anticholinergic effects: dry mouth, blurred
vision, constipation & urine retention,
aggravation of glaucoma
2- Antihistaminic effects: Sedation, confusion
Sedation wear off in 1-2 weeks as the anti-
depressant effect develops
5- Metabolic-endocrine: weight gain, sexual
disturbances

30. 3- CV effects: postural hypotension, due to
blockade of α-adrenoceptors and reflex tachycardia
4- Neurologic: seizures
5- TCAs have narrow therapeutic index.
6- Depressed patients tend to be suicidal
7- may be fatal in overdose (arrhythmia)

31. Selective Serotonin
Reuptake Inhibitors

32. Selective Serotonin Reuptake Inhibitors: SSRI’s
# First highly selective 5HT-reuptake inhibitors
# Little or no effect on NE reuptake
# First choice for most depression
# Clinical efficacy for major depression resembles that of the TCAs

33. Mechanism of Action .

34. SSRI’s * Fluoxetine (Prozac) prototype of SSRIs *Sertraline
*Paroxetine
*Fluvoxamine
*Citalopram
* Escitalopram
النموذج

35. Advantages of SSRIS No blocking actions at M or α1 receptors,
1- SSRIs are much safer in overdose than
other antidepressants
2- They lack many of the adverse effects
of TCAs and MAOIs
No blocking actions at M or α1 receptors,
H1 receptors
*Better side effect profile 2-
Fluoxetine is approved for use in children
& adolescence and is relatively safe in pregnancy

36. Side effects
1- GIT adverse effects are common : GIT upset , nervousness, insomnia
2- Diminished sexual functions
3- Headache and sleep disturbances
4- Long-term weight gain
5- CVS side effects are minimal
# Many side effects disappear after the adaptation phase, when the antidepressant effects begin ( up to 6 weeks).
# Side effects and their durations are highly individual and drug-specific. 
A number of drugs are not associated with sexual side effects (such as bupropion, mirtazapine and maprotiline,
As a result, sexual dysfunction caused by SSRIs can sometimes be treated by several different medications. These include:
bupropion (norepinephrine and dopamine reuptake inhibitor)
buspirone (serotonin 5-HT1A receptor partial agonist)
Mirtazapine

37. Therapeutic Uses 1- Major depression, Generalized anxiety disorder
(GAD) and panic disorders
2- Obsessive-Compulsive Disorder
3- Some eating disorders (bulimia)
4- Premenstrual syndrome
5- Anorexia nervosa
6- Premature ejaculation
6- Premenstrual syndrome.
7- Alcohol abuse.
8- Anorexia nervosa.
9- Generalized anxiety disorder (GAD).

38. Drug Interactions A dangerous pharmaco- dynamic interaction may occur
when fluoxetine is used with
MAOIs leading to the
serotonin syndrome

39. “Serotonin Syndrome” Life-threatening condition resulting from
overstimulation of serotonin receptors
This can occur when two antidepressants
are taken together (multiple different
mechanisms of serotonin elevation)
Symptoms: Autonomic instability
( BP , pulse, temperature)
mental confusion, shivering
sweating, rigidity/hypertonia and diarrhea

40. .

41. To minimize the risk of serotonin syndrome
*There must be a 'washout' period of
at least two weeks when switching
from one antidepressant drug to another
(It is necessary to clear the system
completely of one drug before starting
another