The document discusses depression as a common psychiatric disorder characterized by prolonged sadness, mood changes, and various emotional and biological symptoms. It classifies depression into types and severities, outlines treatment options including psychological and pharmacological approaches, and details different classes of antidepressants and their mechanisms. Lastly, it addresses the use of electroconvulsive therapy for severe cases and highlights the importance of neurotransmitter functioning in mood regulation.

1. DEPRESSION AND
ANTIDEPRESSANT
S DRUG

2.  INTRODUCTION
 SYMPTOMS OF DEPRESSION
 CLASSIFICATION OF DEPRESSION
 TREATMENT OF DEPRESSION
 ANTIDEPRESSANTS
 ELECTROCONVULSIVE THERAPY

3. Introduction

4. "Depression" is a very common psychiatric
disorder that is related to the "mood"
(affective disorder).
 Changes in mood are associated with
depression and/or mania.
 Disorders of mood rather than disturbance in
thought or cognition.
 Clinical depression: feeling sad for more than
two weeks.

5. 1- Emotional Symptoms
 Intense feelings of sadness,
hopelessness and despair
 Inability to experience ordinary pressure or
to cope with ordinary life events
 Feeling of guilt and ugliness
 Indecisiveness and loss of motivation
 Loss of energy and interest

6. 2- Biological symptoms
1- Retardation of thought and action
2- Loss of libido
3- Loss of appetite and sleep
disturbance
DEPRESSION IS THE MOST COMMON CAUSE OF
SUICIDE

7. Classification of Depression
A) According to severity of symptoms:
1. Mild depression---------self-limiting
2. Moderate depression -------difficulties at
home and work
3. Severe depression --------serious,
associated with suicidal thoughts

8. B) According to type
1- Unipolar depression (major depression):
 mood swings are always in the same direction
 about 75% of cases non-familial
 accompanied by symptoms of anxiety and agitation
 Associated with stressful life events
 25% familial
 unrelated to external stresses
 endogenous depression
2- Bipolar depression (manic-depression):
 in which depression alternates with mania
 enthusiasm and self-confidence, accompanied by
impulsive actions

9. I. Psychotic depression
II. Postpartum depression
III. Atypical depression
What are the possible mechanisms of
depression?
• Depression is associated with insufficient
central release of NA and 5-HT
• Led to development of the Biogenic Amine
Hypothesis

10.  Proposed in 1965 and states that DEPRESSION is
caused by a functional deficit of Monoamine
transmitter at certain sites in the brain, while MANIA
results from functional excess.
 The Theory is based on the ability of known
antidepressat drugs (TCAs and MAOIs) to facilitate
monoaminergic transmission and of drugs as
Reserpine to cause depression.

11. Normal synapse, no depression.

12. Neurotransmitter deficiency
lead to Depression

13.  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
 However, dopamine is important for
pleasure, sex & psychomotor activity

14. TREATMENT OF DEPRESSION
1. Psychological treatment
2. Pharmacological treatment
70 % of depressed patients respond to
antidepressants
3. ECT ( electroconvulsive therapy)
for very severe depression, which has not
responded to other treatments or for patients who
cannot take antidepressants

15. ANTIDEPRESSANTS
 Antidepressants do not act immediately (show
clinical effects after 2 weeks) indicating that
secondary adaptive changes in the brain are
important.
 The most consistent adaptive change seen with
antidepressant drugs is the downregulation of beta-,
alpa-2 and 5-HT2 receptors. Alpha-1 is not affected.
 Affect only people who are depressed.
 Effect does not increase with increasing doses.
 Antidepressants are not habit-forming.
 Antidepressants differ widely in side effects.

16. 1) Tricyclics (TCAs) and Tetracyclics
Imipramine Doxepin Desipramine
Amoxapine Trimipramine
Maprotiline Clomipramine Amitriptyline
Nortriptyline Protriptyline
2) Monoamine Oxidase Inhibitors (MAOIs)
Tranylcypramine Phenelzine Moclobemide
3) Selective Serotonin Reuptake Inhibitors (SSRIs)
Fluoxetine Fluvoxamine
Citalopram
Sertraline Paroxetine Escitralopram

17. 4) Serotonin and Norepinephrine Reuptake Inhibitor
(SNRI)
Venlafaxine Duloxetine
5) Norepinephrine and Dopamine Reuptake Inhibitor
(NDRI)
Bupropion
6) Noradrenaline Reuptake Inhibitor (NRI)
Reboxetine
7) Serotonin Reuptake Enhancer
Tianeptine

18.  TCAs are the oldest class of
antidepressant drugs
 They have characteristic three-ring
nucleus
 The first TCAs discovered was
Imipramine
Imipramine
(Tofranil)

19.  Imipramine Desipramine
 Clomipramine Amitriptyline
 Nortriptyline Doxepin
 Trimipramine
TETRACYCLIC ANTIDEPRESSANTSTETRACYCLIC ANTIDEPRESSANTS
 Maprotiline
 Amoxapine

20. Blocking of receptors
 TCAs also block :
 Serotonergic receptors
 Alpha adrenergic receptors
 Histaminic receptors
 Muscarinic receptors
 Their role in therapeutic benefit is not
known
 These actions produce the adverse effects

21. 1- Elevate mood
2- Improve mental alertness
3- Increase physical activity
# The antidepressant effect may develop after several
weeks of continued treatment ( 2 - 3 weeks)
4- In non-depressed patients They cause
sedation, confusion & motor incoordination

22. PHARMACOKINETICS of TCAs
TCAs are "lipophilic" in nature, therefore they are well
absorbed from the GIT and readily cross the blood
brain barrier to penetrate the CNS.
Elimination: hepatic oxidation
TCAs are strongly bound to plasma proteins.
Average t1/2: 24 hours ( 72 hours in overdose)
Large T1/2 and large VD because TCA extensively
bound to plasma protein
(90-95 %)

23.  Amongst the first Antidepressants
 Include:
- Phenelzine
- Tranylcypromine
- Isocarboxazid
- Moclobemide
- Pargyline
 Onset of antidepressant effect is delayed
for 2-4 weeks.

24.  MAO is found in nearly all tissues and is located
intracellularly associated with mitochondria.
 Present in nerve terminals that release NA, DA or 5-
HT.
 Located on outer surface of mitochondrial
membranes.
 In neurons, MAO oxidatively deaminates and
inactivates any excess norepinephrine, serotonin
and dopamine, that may leak out of synapstic
vesicles.
 MAO is not involved in the inactivation of released
transmitter

25. MAO exists in tow forms coded by separate
genes
MAO-A: Metabolizes norepinephrine, serotonin
and tyramine.
Inhibition of MAO-A produces Antidepressant
effect .
MAO-B: specific for dopamine.
Inhibition of MAO-B produces Anti-parkinsonian
effect.

26.  This occurs when Tyramine rich foods are taken
with MAOIs.
 Tyramine rich foods include Old cheese ,
Concentrated yeast products, Pickled or smoked
fish, Red beans, Red Wine, Chicken liver,
Sausages.
 Tyramine in food is normally degraded in the gut by
MAO-A.

27. - Fluoxetine (prozac)
- Fluvoxamine
- Paroxetine
- Sertraline
- Citalopram
- Escitalopram

28. .
Mechanism of Action of SSRIs

29. Adverse effects of SSRIs:
 GIT symptoms: Nausea vomiting & diarrhea.
 Changes in appetite ---weight loss/ gain.
 Sleep disturbances: Drowsiness with
Fluvoxamine.
 Anxiety & Tremors.
 Sexual dysfunction: Loss of libido , delayed
ejaculation.
Discontinuation syndrome:
 Symptoms are headache ,malaise & flu like
symptoms, agitation , irritability & nervousness

30. NE SELECTIVE REUPTAKE INHIBITORS
(NRIS)
Reboxetine
Tomoxetine
 Selective to NE uptake
 May be more effective in noradrenaline deficiency syndrome
(e.g., depression associated with fatigue, apathy, cognitive
disturbances), or non responders to SSRIs.
 Also act at presynaptic α2, postsynaptic α1, α2 and β
adrenergic receptors (tremor, agitation, blood pressure).
Advantages
 Lacks antagonistic activity at histamine H1,
muscarinic & adrenergic receptors or Na+ pump as
with TCA.
 Fewer unwanted cardiovascular effects than TCA’s.

31.  Serotonin norepinephrine reuptake inhibitors
(SNRIs) are a class of antidepressant used in
the treatment of clinical depression and other
affective disorders.
 They act upon two neurotransmitters in the brain
that are known to play an important part in
mood, namely, 5HT and NE. This can be
contrasted with the more widely-used selective
serotonin reuptake inhibitors (SSRIs), which act
only on serotonin.

32. Venlafaxine
• It is used primarily for the treatment of depression, generalized
anxiety disorder, and social anxiety disorder in adults.
Venlafaxine is the first and most commonly used SNRI.
• Selective 5HT and NE uptake blockers Combines the action of
SSRI and NRI.
• Causes dual action on serotonin and adrenergic
systems, thus amplifying these two systems
synergistically.
• But without α1, M1 cholinergic or H receptor
blocking properties.
Venlafaxine

33.  Stimulation through electrodes placed on
either side of the head with the patient
anaesthetized, paralysed with a NMB drugs
to avoid physical injury and artificially
ventilated
 Response rates 60-80 %
 The most effective treatment
for severe suicidal depression
 DISADVANTAGES
Confusion, Memory loss lasting
for days or weeks