Antidepressant Drugs: An Updated Overview
These medications modulate neurotransmitters (Serotonin, Norepinephrine, Dopamine) to restore chemical balance and alleviate symptoms of depression and anxiety.
Author: Islam Ennaquib
Efficacy Snapshot:
40–60% of individuals taking SSRIs or SNRIs experience symptom relief within 6–8 weeks, with benefits being more pronounced in severe depression.
7 Major Classes of Antidepressants
5-HT
Selective Serotonin Reuptake Inhibitors (SSRIs)
First-Line Agents
- MOA: Blocks reuptake of **Serotonin**, increasing synaptic concentration.
- Rx: Fluoxetine (Prozac), Sertraline (Zoloft), Citalopram (Celexa).
- Adverse: Sexual dysfunction, Nausea, Headache, QTc prolongation.
Dual
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Dual Action
- MOA: Blocks reuptake of both **Serotonin** and **Norepinephrine**.
- Rx: Duloxetine (Cymbalta), Venlafaxine (Effexor XR), Milnacipran.
- Adverse: Nausea, Sexual dysfunction, **Increased Blood Pressure**.
M1
Tricyclic Antidepressants (TCAs)
Broad Receptor Affinity
- MOA: Inhibits **NE** and **5-HT** reuptake; blocks M1/H1 receptors.
- Rx: Amitriptyline, Imipramine (Tofranil), Nortriptyline (Pamelor).
- Adverse: Dry mouth, Drowsiness, **Cardiac Rhythm Problems**, Weight gain.
🚫 MAO
Monoamine Oxidase Inhibitors (MAOIs)
For Treatment-Resistant Depression
- MOA: Inhibits MAO enzyme, increasing all **Monoamines** (5-HT, NE, DA).
- Rx: Phenelzine (Nardil), Isocarboxazid (Marplan), Selegiline (Emsam).
- Adverse: Risk of **Hypertensive Crisis** (Tyramine food/drug interactions).
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Atypical Antidepressants (Misc.)
Diverse Mechanisms
- MOA: **Varies.** Bupropion (DA/NE), Mirtazapine (Alpha-2 blocker, 5-HT Antagonist).
- Rx: Bupropion (Wellbutrin), Mirtazapine (Remeron), Agomelatine.
- Adverse: Bupropion: Seizures. Mirtazapine: Sedation/Weight gain. Agomelatine: Hepatotoxicity.
5-HT₂
Serotonin Modulators
Receptor Specific
- MOA: Targets **5-HT Receptors** (e.g., 5-HT2A antagonism, 5-HT1A agonism).
- Rx: Trazodone, Vilazodone, Vortioxetine, Nefazodone.
- Adverse: Trazodone: Sedation/Priapism. Nefazodone: Hepatotoxicity.
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NMDA Antagonists
Glutamatergic Modulation (Rapid Onset)
- MOA: Modulates **Glutamate** activity via the NMDA receptor.
- Rx: Esketamine (Spravato), Dextromethorphan-Bupropion (Auvelity).
- Adverse: Dissociation, Sedation, Nausea, Blood pressure increase.
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