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Updated: Dec 29 2021

Selective Serotonin Reuptake Inhibitors (SSRIs)

  • Snapshot
    • A 64-year-old female was brought to her primary care physician by her daughter due to poor appetite. When eliciting a history, you learn that the patient no longer finds joy in her hobbies, has feelings of worthlessness, is unable to sleep, and has issues concentrating. In addition to psychotherapy, the patient is prescribed sertraline.
  • Introduction
    • SSRIs are commonly considered first-line treatment for depression
      • likely through increasing serotonergic activity
      • usually takes 3-8 weeks for therapeutic effects to occur
  • Treatment
    • Drugs
      • citalopram
      • escitalopram
      • fluoxetine
      • fluvoxamine
      • paroxetine
      • sertraline
    • Mechanism
      • likely through decreasing the serotonin reuptake pump in presynaptic neurons
        • this in turn increases synaptic serotonin availability and serotonin receptor occupancy in postsynaptic neurons
        • serotonin reuptake receptor selectivity → relatively benign side-effects
      • cytochrome P450 inhibitor
        • citalopram and escitalopram are the SSRI of choice if you're concerned about drug-to-drug interactions
    • Clinical use
      • major depressive disorder (MDD, first-line treatment)
      • obsessive-compulsive disorder
      • post traumatic stress disorder
      • panic disorder
      • generalized anxiety disorder
      • bulimia nervosa
      • binge eating disorder
      • social phobias 
      • hoarding disorder 
    • Toxicity   
      • much milder than other depression therapies
      • weight gain
        • fluoxetine has lowest risk
      • can cause QTc prolongation
      • anxiety, agitation, and insomnia
      • GI distress
      • sexual dysfunction (anorgasmia)   
        • can use alternative antidepressants such as bupropion and mirtazapine
      • acute increased risk of suicidal behavior (FDA black box warning) 
        • due to "energizing phenomenon," where patients have increased energy to act on suicidal ideation, prior to improvement of mood symptoms
        • most common in pediatric populations
      • serotonin syndrome
        • anxiety, restlessness, disorientation, autonomic manifestations (i.e., diaphoresis, hyperthermia, hypertension), and neuromuscular hyperactivity (i.e., myoclonus, hyperreflexia, muscle rigidity, tremor)
      • SSRI discontinuation syndrome
        • with abrupt discontinuation of the medication
        • fluoxetine is less likely to cause symptoms post abrupt discontinuation
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