Psychopharmacology: SSRIs and SNRIs

Antidepressant Drugs

• Classification of antidepressants:
  • Tricyclic antidepressants (TCA)
  • Selective serotonin re-uptake inhibitors (SSRIs)
  • Serotonin/norepinephrine re-uptake inhibitors (SNRIs)
  • Atypical antidepressants
  • Monoamine oxidase inhibitors (MAOIs)

Tricyclic Antidepressants (TCA)

• Mechanism of action:
  • Inhibit pre-synaptic neuronal reuptake of NA & 5HT, leading to accumulation of these transmitters in the synaptic clefts in the brain
• Pharmacokinetics:
  • Well absorbed orally
  • High 1st pass effect
  • Pass the blood-brain barrier (BBB)
  • Metabolized in the liver
  • Conjugated with glucuronic acid and excreted in urine
• Pharmacological effects:
  • Antidepressant
  • Sedation (amitriptyline > imipramine > desipramine)
  • Anticholinergic (amitriptyline > imipramine > desipramine)
  • Antihistamine (H1 & H2 blockers)
  • Alpha1 blocking action, leading to postural hypotension
• Therapeutic uses:
  • Depression
  • Obsessive compulsive disorders (clomipramine or fluvoxamine is better)
  • Panic and phobic states
  • Chronic pain
  • Nocturnal enuresis (anticholinergic action)
  • Peptic ulcer (doxepin), blocks muscarinic & H2 receptors
  • Attention deficit syndrome in children
• Side effects:
  • Anticholinergic (atropine-like) action
  • Sympathomimetic effects
  • CNS: sedation, tremors, confusion, delirium, and seizures
  • CVS: postural hypotension, arrhythmia, tachycardia, and cardiomyopathy
  • Weight gain

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Advantages:
  • No sedation
  • No anticholinergic effects
  • No postural hypotension
  • No weight gain
  • Less delay in the onset of action
  • Effective in resistant cases to TCA & MAOI
• Uses:
  • Mild to moderate depression
  • Obsessive compulsive disorders (fluvoxamine)
  • Bulimia (increased desire to eat)

Serotonin/Norepinephrine Re-uptake Inhibitors (SNRIs)

• Venlafaxine and duloxetine
• Treat cases of depression which are resistant to SSRIs
• Treat depression accompanied by neuropathic pain
• No activity at adrenergic, muscarinic, or histamine receptors, resulting in fewer adverse effects than TCA
• Duloxetine is contraindicated in hepatic insufficiency and end-stage renal disease

Atypical Antidepressants

• Have action at several different sites
• Not more efficacious than TCAs or SSRIs, but have different side effects profiles
• Include:
  • Bupropion
  • Mirtazapine
  • Nefazodone and trazodone

Bupropion

• Inhibits noradrenaline and dopamine reuptake
• Decreases craving for nicotine in tobacco abusers
• Side effects: dry mouth, sweating, tremor, and seizures at high doses

Mirtazapine

• Blocks presynaptic alpha2-receptors, increasing NA and serotonin
• Blocks 5HT2 receptors
• May cause sedation and weight gain

Nefazodone and Trazodone

• Weak serotonin reuptake inhibitors
• Block postsynaptic 5-HT2 receptors
• Both agents block H1-receptors, leading to sedation
• Trazodone blocks α1, leading to priapism

Monoamine Oxidase Inhibitors (MAOIs)

• Hydrazine group: phenelzine, isocarboxazid
• Non-hydrazine group: tranylcypromine, moclobemide, and clorgyline
• Selegiline

Amine Hypothesis of Mood

• Psychic depression: decrease in concentration of noradrenaline and serotonin in the brain
• Elevated mood: increase in noradrenaline and serotonin in the brain
• Schizophrenia: increased dopamine in the brain

This quiz covers the effects and side effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in treating depression, anxiety, and other disorders.