This document discusses antidepressants and their mechanisms and uses. It first outlines several hypotheses for the causes of depression, including reduced levels of neurotransmitters like serotonin, norepinephrine, and dopamine. It then describes the types of antidepressants, focusing on tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). TCAs act on both serotonin and norepinephrine, while SSRIs only target serotonin. The document contrasts TCAs and SSRIs, noting that TCAs have a narrower therapeutic index and greater side effects like dry mouth and arrhythmias, while SSRIs have fewer side effects and a wider safety margin. Finally, it lists several approved indications

1. ANTIDEPRESSANTS

2. Depression – most common psychiatric
disorder
Depression – 3 to 5% of population is
depressed
Life time prevalence – around 10%

3.  Lowered mood, varying from mild sadness to
intense feelings of guilt, worthlessness, and
hopelessness.
 Difficulty in thinking, including inability to
concentrate, and lack of decisiveness.
 Loss of interest, with diminished involvement in
work and recreation.

4.  Somatic complaints such as headache; disrupted,
lessened, or excessive sleep; loss of energy; change in
appetite; decreased sexual drive.
 Delusions of a hypochondriacal or persecutory
nature.
 Withdrawal from activities.
 Suicidal ideation.

5. Monoamine Hypothesis of
Major Depression
• Involves brain monoamines
– Norepinephrine (NE)
– Serotonin (5-HT)
– Dopamine (DA)
• Hypothesis says
– Functional  in amount or function of cortical and
limbic serotonin, norepinephrine and
dopamineresulting in depression

6.  Drugs that deplete monoamines are depressant.
 Most antidepressants enhance monoaminergic
transmission at some point in the synaptic signaling
process.
 The concentration of monoamines and their
metabolites is reduced in the CSF of depressed
patients.

9. Neurotrophic hypothesis
• BDNF - Brain derived neurotrophic factor
• Regulation of neural plasticity and neurogenesis
• Depression – loss of neurotropic support
• Effective AD increase neurogenesis.

10. Neurotrophic hypothesis
Stress and pain
Decrease in BDNF
Decrease in neurotropic support
Atrophy of hippocampus, cingulate gyrus,
medial frontal cortex
Depression

11. Neuroendocrine hypothesis
Elevated
cortisol levels
Thyroid
dysregulation
Estrogen
deficiency Testosterone
deficiency

12. TRICYCLIC ANTIDEPRESSANTS
Amitriptyline
Nortriptyline
Protriptyline
Imipramine
Trimipramine
Doxepin
SSRI
Fluoxetine
Paroxetine
Fluvoxamine
Sertraline
Citalopram

13. SEROTONIN NOREPINEPHRINE
REUPTAKE INHIBITORS
Duloxetine
Venlafaxine
MAO I
Phenelzine
Tranylcypromine
5 HT2 ANTAGONISTS
Nefazodone
Trazodone
TETRACYCLICS
Bupropion
Mirtazapine
Maprotiline

14. Tricyclic Antidepressants (TCAs)
• Characteristic three ring nucleus.
Mechanism of Action:
- Inhibition of NT and 5 HT reuptake.
- Immediate action = > NE and 5-HT in synapse.
- Takes up to 4 weeks for all TCA antidepressants to
have an effect
Tricyclic Antidepressants (TCAs)

15. Side Effects:
• Atropine-like side effects: dry mouth,
constipation, blurred vision, mydriasis,
metallic taste, urine retention => muscarinic
blockade.
• Orthostatic hypotension => 1-AR blockade.
• Drowsiness, sedation and weight gain =>
Histamine-Receptor blockade.
Tricyclic Antidepressants (TCAs)

16. Side Effects (con’t):
• Most serious side effect is cardiac toxicity.
• Sexual dysfunction, including loss of libido,
impaired erection and ejaculation and
anorgasmia
.  COMPLIANCE
Tricyclic Antidepressants (TCAs)

17. Other effects (con’t):
• Can lower seizure threshold.
• All potentiate CNS depressants (BZDs, Barbs,
ETOH) => coma and death.
• TCA administration in bipolar disorder may
precipitate acute mania or rapid cycling.
• Fatal in overdose (a 2 wk supply can kill anyone).
Tricyclic Antidepressants (TCAs)

18. • Drugs quite effective.
– Decline in use not related to efficacy
– Have low margin of safety in overdose, poor adverse
reaction profiles and drug interaction profiles.
– Children and elderly particularly susceptible
• Display
– M1, H1, 1 blockade
– ADR:
• Dry mouth, constipation, urinary retention, sinus tachycardia,
blurred vision, postural hypotension, sedation, sexual dysfunction.
• Quinidine-like effects on cardiac conduction
• Cost effective

19. What are the indications for
antidepressants?

20. Indications
• Depression
• Anxiety disorders
– Obsessive Compulsive disorder
– Generalised Anxiety Disorder.
– Post traumatic stress disorder
– Social phobia
– Panic disorder

21. Indications
• Migraine.
• Smoking deaddiction
• Diabetic neuropathy

22. Indications
• Chronic pain syndrome.
• Bulimia nervosa.
• Nocturnal enuresis.
• Pruritus.

23. Compare and contrast TCA
and SSRI

24. TCA SSRI
Acts on both NE and 5 HT
reuptake. Prevents
reuptake of both NE and 5
HT
Selectively prevents
reuptake of 5 HT.
Narrow therapeutic index Wider therapeutic index
Used in severe depression
not responding to SSRI
First choice drug for
depression
Can cause weight gain Less prone to cause weight
gain

25. TCA SSRI
Decreases threshold for
seizures
Less chance for provoking
seizures
Can cause arrhythmia.
Unsafe in HD
Safe in HD
Postural hypotension in
elderly
No postural hypotension