Antidepressants

Antidepressants are drugs that treat depression by balancing neurotransmitters like serotonin, norepinephrine, and dopamine.

Definition of Antidepressants:

• Drugs that elevate mood in depression, anxiety, OCD, and PTSD.
• Used to treat major depressive disorder (MDD), anxiety disorders, OCD, PTSD, and some types of chronic pain.

Classification of Antidepressants:

1. Selective Serotonin Reuptake Inhibitors (SSRIs)

   • Inhibit reuptake of serotonin (5-HT) in the synaptic cleft
   • Considered first-line due to fewer side effects
   • Examples:
     • Fluoxetine
     • Sertraline
     • Escitalopram
     • Paroxetine

2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

   • Inhibit reuptake of both serotonin and norepinephrine
   • Examples:
     • Venlafaxine
     • Duloxetine

3. Tricyclic Antidepressants (TCAs)

   • Inhibit reuptake of norepinephrine and serotonin
   • Also affect histamine, muscarinic, and alpha receptors, leading to more side effects
   • Examples:
     • Amitriptyline
     • Imipramine
     • Nortriptyline

4. Monoamine Oxidase Inhibitors (MAOIs)

   • Inhibit monoamine oxidase, an enzyme that breaks down serotonin, norepinephrine, and dopamine
   • Reserved for treatment-resistant depression
   • Examples:
     • Phenelzine
     • Tranylcypromine

5. Atypical Antidepressants

   • Diverse mechanisms
   • Examples:
     • Bupropion: inhibits norepinephrine and dopamine reuptake
     • Mirtazapine: antagonizes alpha-2 receptors to increase NE and 5-HT release
     • Trazodone: 5-HT2A antagonist, causes sedation

Therapeutic Uses:

• Major depressive disorder
• Anxiety disorders (GAD, panic, OCD)
• Neuropathic pain (TCAs, SNRIs)
• Smoking cessation (Bupropion)

Adverse Effects:

• SSRIs/SNRIs: gastrointestinal upset, sexual dysfunction, insomnia, headache
• TCAs: sedation, dry mouth, blurred vision, orthostatic hypotension, arrhythmias
• MAOIs: hypertensive crisis if combined with tyramine-containing foods (e.g., cheese, wine)

Pharmacokinetics:

• Most are orally administered
• Highly protein-bound, metabolized in liver
• Delayed onset (2–4 weeks)

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