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SSRIs

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Summary

Selective serotonin reuptake inhibitors (SSRIs) are drugs used for a variety of psychiatric disorders. Important SSRIs to know include the drugs paroxetine, fluoxetine, escitalopram, citalopram, and sertraline. As their name suggests, these drugs work to increase serotonin signaling in the brain, by blocking the reuptake or transport of serotonin out of the synapse. SSRIs are the first-line or preferred treatment for patients with depression and anxiety disorders. The most important side effects of taking SSRIs include sexual dysfunction and serotonin syndrome. 

Key Points

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
    • Drug Names
      • Fluoxetine, Paroxetine
      • Sertraline
      • Escitalopram, Citalopram
      • Fluvoxamine
    • Mechanism
      • Block serotonin (5-HT) reuptake
        • Inhibit reuptake transporters on presynaptic neurons, increasing serotonin levels in the synaptic cleft
      • Typically take 4-8 weeks to take effect
        • SSRIs must be taken for at least 6 weeks before evaluating efficacy of therapy
    • Indications
      • Depression
        • First-line treatment for major depression, along with CBT
        • May also be used for depression with atypical features, and  premenstrual dysphoric disorder or postnatal depression
      • Anxiety disorders
        • First-line treatment (along with CBT) for a wide variety of anxiety disorders, including:
          • Generalized anxiety disorder
          • PTSD
          • Panic disorder
          • Obsessive-compulsive disorder
          • Social anxiety disorder (includes agoraphobia)
      • Eating disorders
        • Second-line for bulimia nervosa and binge-eating disorder
        • May be used in addition to CBT
      • Adjustment disorder (depressed mood)
        • May be used if resistant to CBT/psychotherapy
      • Selective mutism
        • In addition to behavioral therapy
      • Premature ejaculation
        • Takes advantage of anorgasmia side effect
    • Adverse Effects
      • Serotonin syndrome
        • Overload of serotonin signaling that classically occurs when taking SSRIs with other serotonin-modulating drugs (e.g. TCAs, MAOIs, Linezolid)
        • Characterized by a clinical triad:
          • Hyperactivity (clonus, hyperreflexia, hypertonia, seizures)
          • Autonomic instability (high temperature, sweating, tachycardia, diarrhea)
          • Altered mental status
        • Tip: Differentiate from neuroleptic malignant syndrome (NMS) due to the presence of absence of hyperreflexia and clonus. If clonus, think serotonin syndrome. If a patient has rigid muscles with no clonus, think NMS!
        • Treat with Cyproheptadine (5-HT2 receptor antagonist)
      • Sexual dysfunction
        • Anorgasmia, low libido
      • Antidepressant discontinuation syndrome
        • Discontinuing an SSRI requires a taper. A sudden discontinuation or rapid dose reduction can produce flu-like symptoms
      • GI distress
        • Diarrhea, nausea/vomiting when first starting an SSRI
      • SIADH
        • Not recommended in the elderly given increased risk of SIADH
      • Sleep effects
        • Reduces duration of REM sleep
        • Increases time it takes to enter REM sleep (latency)