SSRIs

Summary

The SSRIs, or selective serotonin reuptake inhibitors, include the drugs fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, and escitalopram.

SSRIs work by blocking the reuptake of serotonin, thereby increasing serotonin levels in the brain. However, their full clinical effects are delayed and usually take 4-8 weeks to manifest.

Clinically, SSRIs are used to treat a variety of conditions, including depression, premenstrual dysphoric disorder, generalized anxiety disorder, PTSD, social anxiety disorder, panic disorder, OCD, as well as eating disorders like binge-eating disorder and bulimia. They may also be used to treat selective mutism and premature ejaculation.

Side effects of SSRIs can include flu-like symptoms if the drug is stopped suddenly, precipitation of mania in patients with bipolar disorder, SIADH, sexual dysfunction, serotonin syndrome, and GI distress.

Key Points

• Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Drug Names
    • Fluoxetine
    • Fluvoxamine
    • Paroxetine
    • Sertraline
    • Escitalopram
    • Citalopram
  • 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 show appreciable effect
      • SSRIs must be taken for at least 6 weeks before evaluating efficacy of therapy
  • Clinical Use
    • Treats depression
      • First-line treatment for major depression, along with CBT
      • May also be used for:
        • premenstrual dysphoric disorder
        • depression with atypical features
        • adjustment disorder
        • postnatal depression
    • Treats 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 (OCD)
        • Social anxiety disorder
          • Includes agoraphobia (fear of open spaces or situations in which escape isn’t possible)
    • Premature ejaculation
      • Takes advantage of anorgasmia side effect
    • Eating disorders (e.g. bulimia)
      • Second-line for bulimia nervosa and binge-eating disorder
      • May be used in addition to CBT
    • Selective mutism
      • Type of anxiety disorder involving refraining from speech
      • In addition to behavioral therapy
  • Side 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 (impotence)
      • Anorgasmia, erectile dysfunction, low libido
    • GI distress
      • Diarrhea, nausea/vomiting when first starting an SSRI
    • SIADH
      • Not recommended in the elderly given increased risk of SIADH
    • May precipitate mania in underlying bipolar disorder
    • Antidepressant discontinuation syndrome
      • Discontinuing an SSRI requires a taper. A sudden discontinuation or rapid dose reduction can produce flu-like symptoms