Anti depressants

1. Anti-depressants
Dr. Sajjad Ali
Pharm-D, R.Ph., M.Phil.
(Pharmacology)

2. Definition of Depression
• Depression is a mental disorder which is
characterized by loss of interest or
pleasure in almost all a person’s usual
activities.

7. Amine hypothesis of mood
• According to this hypothesis brain amines
particularly norepinephrine (NE) and
serotonin (5-HT) are neurotransmitters
those are involved in expression of mood
• Functional decrease in the activity of such
amines(Particularly Serotonin) is thought
to result in depression

9. Drugs for the treatment of
Depression
1. Tricyclic anti-depressants (TCAs)
 Clomipramine
 Imipramine
 Amitriptyline
 Nortriptyline
2. SSRIs (Selective serotonin reuptake inhibitors
 Escitalopram
 Fluoxetine
 Paroxetines
 sertraline

10. 3. SNRIs (Serotonin nor-epinephrine reuptake
inhibitors)
 Doluxetine
 Venlafaxine
4. MAO Inhibitors
 Phenelzine
 Selegiline
 tranycypromine

11. 5. Heterocyclic anti-depressants
• Bupropion
• Amoxapine
• mirtazapine

13. Tricyclic Anti-depressants
(TCAs)
Imipramine
Desipramine
Nortriptyline
Amitriptyline
Clomipramine

14. Tricyclic Antidepressants
• Effectively relieve depression with
anxiolytic and analgesic action
Mechanism of Action
– Block presynaptic NE reuptake transporter
– Block presynaptic 5-HT reuptake transporter
– Block histamine receptors
– Block ACh receptors

15. Pharmacokinetics
• Well absorbed upon oral administration
• Relatively long half-lives
• Metabolized in the liver
• Converted into intermediates that are later
detoxified
• Readily cross the placenta

16. Pharmacological Effects of TCA’s
• In CNS: blocks presynaptic 5-HT and NE
receptors
• Blocking of ACh receptors leads to dry mouth,
confusion, blurry vision and mental confusion
• Blocking of histamine receptors leads to
drowsiness and sedation

17. Side effects of tricyclic Anti-
depressants
• drowsiness and sedation
• dry mouth
• Confusion
• blurry vision
• mental confusion
• Postural hypotension
• Tachycardia
• Sweating
• Agitation

18. • Overdose of TCAs is extremely hazardous
• It may cause convulsions, circulatory
collapse and respiratory depression

19. SSRI’s (Selective serotonin
reuptake inhibitors)
• Fluoxetine – first SSRI available, long half life, slow
onset of action.
• Sertraline – second SSRI approved, low risk of toxicity,
few interactions, more selective and potent than
Fluoxetine
• Paroxetine – third SSRI available, more selective than
fluoxetine, highly effective in reducing anxiety and
posttraumatic stress disorder (PTSD) as well as OCD,
panic disorder, social phobia, premenstrual dysphoric
disorder, and chronic headache

20. Mechanism of action
• SSRIs have highly selective action on
serotonin transporter. Thus selectively
inhibits the uptake of serotonin into the
nerve endings
• They have minimal blocking effect on
adrenergic and cholinergic receptors

21. Clinical applications
Used in following conditions;
I.Major depression disorder
II.Anxiety
III.OCD (Obsessive-compulsive disorder)
IV.Premenstrual dysphoric disorder (PMDD)
V.Posttraumatic stress disorder (PTSD)

22. Toxicity
 Nausea, vomiting
 Sexual dysfunction
 Headaches
 Seizures as a result of overdose
 Drug interactions due to inhibition of hepatic cytochrome
P450 iso-zymes
 Serotonin syndrome (when SSRIs are used in
combination with MAOIs)
This is life threatening syndrome which includes severe
muscle rigidity, hyperthermia, CVS instability and marked
CNS stimulatory effects

23. SNRIs (Serotonin Nor-
pinephrine reuptake inhibitors)
• Venlafazine
• Duloxetine
Mechanism of action
 Block both NE and serotonin transporters
 Thus reuptake of both neurotransmitters is
inhibited
 Level of NE and serotonin at synapses
increased

24. Clinical applications
I. Major depression
II. Chronic pain
III. Fibromyalgia
IV. Menopausal symtoms

25. Toxicity
• Anticholinergic effects
• Sedation
• hypertension
• Venlafazine causes dose dependent increase in
blood pressure
• Venlafazine also have CNS stimulatory effects
• Severe withdrawal symptoms occur even after
missing single dose of venlafazine
• Duloxetine causes liver dysfunction

26. Monoamine oxidase inhibitors
(MAOIs)
Selegiline
Phenelzine
Isocrboxaid
Tranylcypromine

27. Mechanism of action
• Inhibit both MAO-A and MAO-B
• Selegiline is more active as MAO-B
inhibitors
• MAO-B involves in the metabolism of
dopamine
• MAO-A involves in the metabolism of NE
and serotonin within presynaptic nerve
endings

28. Clinical Applications
• Major depression disorders which are unresponsive to
other drugs
Toxicity of MAOIs
 Hypertensive reactions when used with
tyramine containing food and sympathomimetic
 Serotonin syndrome with SSRIs
 Insomnia
 Seizures
 hyperthermia

29. Tyramine containing food
• foods containing considerable amounts of
tyramine are chocolate, alcoholic
beverages and fermented foods, such as
most cheeses, soy sauce and soybean
etc.

30. Tyramine-MAOIs drug
interaction
• Tyramine is an amino acid that helps
regulate blood pressure. It occurs naturally
in the body and it's found in certain foods.
Medications called monoamine oxidase
inhibitors (MAOIs) block an enzyme known
as monoamine oxidase, which breaks
down excess tyramine in the body leading
to hypertensive crises.

31. Heterocyclic antidepressants
• Amoxapine
• Bupropion
• Maprotiline
• Mirtazepine

32. Mechanism of action
• Mirtazapine blocks alpha-2 pre-synaptic
receptors
• Mechanism of action of other drugs is
uncertain
Clinical uses
• Used for the treatment of major
depression disorders which are
unresponsive to other drug therapy

33. Toxicity
• Amoxapine and bupropion lower seizures
threshold
• Mirtazepine causes weight gain and
sedation

34. Possible Exam questions
• Define depression and classify drugs for
the treatment of depression
• Write a note on mechanism of action,
clinical uses and side effects of TCAs,
SSRIs and SNRIs