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Article No. 86


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Antidepressants are a class of drugs that are commonly used to treat various psychiatric disorders or presentations such as major depressive disorder, anxiety disorders, eating disorders and even chronic pain, neuropathic pain among many more. 

The mechanism of action of these medications are many and complex:

Mechanism of Action of different antidepressants

Mechanism of Action of different antidepressants

We will review some of the common antidepressants in this article including: Selective Serotonin Reuptake Inhibitors (SSRI), Selective Norepinephrin Reuptake Inhibitors (SNRI), Tricyclic Antidepressants (TCA), Monoamine Oxidase Inhibitors (MAOI).

Selective Serotonin Reuptake Inhibitors

Common Medications:

  • fluoxetine, paroxetine, sertraline, citalopram

Remember these by:

Flashbacks paralyze senior citizens. (fluoxetine, paroxetine, sertraline, citalopram)

Mechanism of Action:

  •  5-HT–specific reuptake inhibitors

Clinical Uses

  • Depression 

  • Generalized anxiety disorder and panic disorders 

  • Obssessive Compulsive Disorder.

Side Effects

  •  GI distress

  • Sexual dysfunction (anorgasmia and decreased libido) 

  • Serotonin syndrome  with any drug that increases 5-HT (e.g., MAO inhibitors, SNRIs, TCAs)

    • Patient presents with hyperthermia, confusion, myoclonus, cardiovascular collapse, flushing, diarrhea, seizures.

    • Treatment: cyproheptadine (5-HT receptor antagonist).

Selective Norepinephrine Reuptake Inhibitors

Common Mediations:

  • Venlafaxine, duloxetine

Mechanism of Action: 

  • Inhibit 5-HT and norepinephrine reuptake

Clinical Use:

  • Major Depression.
  • Venlafaxine is also commonly used for generalized anxiety and panic disorders 
  • Duloxetine is also commonly used for diabetic neuropathy.

Side Effects

  • can increase blood pressure
  • GI upset: nausea

Tricyclic antidepressants

Common Mediations:

  •  Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, amoxapine


Most TCAs end with the suffix -iptyline or -ipramine

Mechanism of Action: 

  •  Inhibit the reuptake of norepinephrine and 5-HT.

Clinical Use:

  • Major Depression
  • Fibromyalgia.
  • Clomipramine can also be used of Obsessive Compulsive Disorder

Side Effects

  •  Sedation, α1 -blocking effects including postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth). 3°  TCAs (amitriptyline) have more anticholinergic effects than 2°  TCAs (nortriptyline) have. Desipramine is less sedating, but has a higher seizure incidence.

  • Anticholinergic side effects

Remember tCa:

Convulsions, Coma, Cardiotoxicity (arrhythmias), Confusion;

TCA Overdose

In a TCA overdose, patients will initially be drowsy and susequently go into cardiac arrest. The arrest is secondary to a ventricular arrhythmia. Prior to arrrest their EKG may look like this:

EKG with feature of a TCA overdose secondary to sodium channel blockade

EKG with feature of a TCA overdose secondary to sodium channel blockade

Patient's will go into cardiac arrest because of a ventricular arrhythmia. You can recognize the abnormality on and EKG prior to the arrest:

  • Interventricular conduction delay:
    • QRS > 100 ms 
  • Findings suggestive of right axis deviation:
    • Terminal R wave > 3 mm in aVR
    • R/S ratio > 0.7 in aVR

Treatment is with sodium bicarbonate.


Monoamine Oxidase Inhibitors

Common Medications:

  • Tranylcypromine, Phenelzine, Selegiline

Mechanism of Action:

  • Nonselective MAO inhibition which will cause an increase levels of amine neurotransmitters (norepinephrine, 5-HT, dopamine), 

Clinical Uses

  • Depression 

  •  Anxiety

Side Effects

  •  Hypertensive crisis (most notably with ingestion of tyramine, which is found in many foods such as wine and cheese);

  • Serotonin Syndrome

    • Do not use MAOIs with SSRIs, TCAs, St. John’s wort, meperidine, and dextromethorphan

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