M06.15.002 Selective Serotonin Reuptake Inhibitors (SSRIs)

Learning Objectives

By the end of this session, the learner will be able to identify the primary SSRIs, explain their mechanism of action, list their broad clinical applications, and recognize the high-yield side effects and toxicities associated with this class.


1. Mechanism and Drugs

SSRIs are the most commonly prescribed antidepressants due to their safety profile and broad efficacy.

Mechanism Common SSRIs
Selective blockade of 5-HT reuptake Fluoxetine, Paroxetine, Sertraline, Citalopram, Escitalopram, Fluvoxamine.

2. Clinical Indications

SSRIs are first-line therapy for various psychiatric conditions beyond major depression.

Condition Clinical Note
Major Depression First-line treatment.
Anxiety Disorders Used for chronic management (GAD, Panic, Phobias).
OCD Often requires higher doses than depression.
Bulimia Nervosa Fluoxetine is specifically indicated.
PMDD Helps manage physical and emotional symptoms of the menstrual cycle.

3. Side Effects and Toxicity

While safer than older antidepressants, SSRIs have specific side effects that often impact patient compliance.

System Side Effect
Sexual Dysfunction Decreased libido, anorgasmia, and erectile dysfunction (common reasons for stopping).
Gastrointestinal Nausea, GI distress (5-HT receptors are abundant in the gut).
CNS Insomnia and agitation.
Hematologic Increased bleeding risk when used with NSAIDs or anticoagulants.

Critical Warning: Serotonin Syndrome

Occurs with overstimulation of 5-HT receptors (often due to drug-drug interactions).

  • Symptoms: Hyperthermia, muscle rigidity, myoclonus, and autonomic instability.
  • Management: Discontinue offending agents; supportive care; Cyproheptadine (5-HT2 antagonist).

Clinical Pearls:

  • SSRIs vs. BZs: Remember that for anxiety, Benzodiazepines provide acute relief, while SSRIs are for long-term prevention.
  • Weight Neutrality: Unlike older TCAs, many SSRIs are relatively weight-neutral, making them more tolerable.
  • Discontinuation Syndrome: Stopping SSRIs abruptly can cause “flu-like” symptoms and “brain zaps.” They should be tapered slowly.

Check Your Knowledge: