Selective Serotonin Reuptake Inhibitor

Aka: Selective Serotonin Reuptake Inhibitor, SSRI

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II. Indications: First Line

  1. Major Depression
  2. Generalized Anxiety Disorder
    1. Fluvoxamine (Luvox)
    2. Paroxetine (Paxil)
  3. Premature Ejaculation
    1. Paroxetine (Paxil)
    2. Sertraline (Zoloft)
    3. Fluoxetine (Prozac)

III. Indications: Adjunctive

  1. Migraine Headache Prophylaxis
    1. Fluoxetine (Prozac)
  2. Diabetic Neuropathy
    1. Paroxetine (Paxil)
  3. Fibromyalgia
    1. Fluoxetine (Prozac)
  4. Neurocardiogenic Syncope
    1. Paroxetine (Paxil)
    2. Sertraline (Zoloft)
    3. Fluoxetine (Prozac)

IV. Adverse Effects: All SSRI

  1. See Antidepressant Adverse Effects
  2. Increased Suicidality in children and teens (FDA black box warning)
  3. Antidepressant Withdrawal and abruptly stopping medications (esp. Paroxetine)
  4. Appetite suppression
  5. Sleep disturbance
  6. Galactorrhea
    1. Lowering Dopamine disinhibits Prolactin
  7. Sexual Dysfunction
    1. See Antidepressant Induced Sexual Dysfunction
  8. Hyponatremia
    1. More common in elderly patients
    2. Consider monitoring Serum Sodium
  9. Upper Gastrointestinal Bleeding in over age 65 years
    1. Average rate: 7.3 per 1000 person years (6.6 - 7.9)
      1. Bleeding risk increased with SSRI potency
    2. Other Risk Factors
      1. Very old patients (where young is age 65 years)
      2. Prior history of Gastrointestinal Bleeding
      3. Diabetes Mellitus
      4. Medications (Coumadin, ASA, NSAIDs, Corticosteroid)
    3. References
      1. Van Walraven (2001) BMJ 323:655-8 [PubMed]
  10. Bleeding risk (antiplatelet activity)
    1. SSRIs interfere with Platelet uptake of Serotonin
    2. Hemorrhagic CVA risk (postmenopausal women): 2.12 Hazard Ratio
      1. Smoller (2009) Arch Intern Med 169(22):2128-39 [PubMed]
    3. SSRI in combination with NSAIDs
      1. Serious upper gastrointestinal event (GI Bleed): 4.19 Adjusted Odds Ratio
      2. Hellin-Salmivaara (2007) Eur J Clin Pharmacol 63:403-8 [PubMed]

V. Precautions

  1. Increased Suicidality in children and teens (FDA black box warning)
  2. Avoid concurrent use with MAO Inhibitor
    1. Risk of Serotonin Syndrome
  3. Pregnancy
    1. Persistent Pulmonary Hypertension
      1. Increased risk by 6 fold if SSRIs used after 20 weeks
      2. Number needed to harm: 286-351
      3. Grigoriadis (2014) BMJ 348:f6932 [PubMed]
    2. SSRIs have shown mixed or weak associations with Autism (as one of many contributing factors)
      1. Boukhris (2016) JAMA Pediatr 170(2):117-2 +PMID:26660917 [PubMed]
      2. Harrington (2014) Pediatrics 133:e1241-8 +PMID:24733881 [PubMed]
      3. Hviid A (2013) N Engl J Med 369:2406-15 [PubMed]
      4. Rai (2013) BMJ 346:f2059 [PubMed]

VI. Adverse Effects: Overdose Symptoms and Signs

  1. See SSRI Overdose
  2. Usually mild and non-life threatening
  3. Cardiovascular effects unlikely (except with Citalopram, Escitalopram)
  4. Nausea or Vomiting
  5. Diarrhea
  6. Dizziness or Somnolence
  7. Seizures
  8. Serotonin Syndrome

VII. Classes: Selective Serotonin Reuptake Inhibitors (SSRI)

  1. Monocyclic
    1. Fluvoxamine (Luvox)
  2. Bicyclic
    1. Fluoxetine HCl (Prozac)
  3. Tricyclic
    1. Sertraline HCl (Zoloft)
  4. Tetracyclic
    1. Paroxetine HCl (Paxil)

VIII. Classes: Other Antidepressants (non-SSRI)

  1. See Antidepressant
  2. Serotonin Modulator and Stimulator (same activity as SSRI)
    1. Vortioxetine (Brintellix)
      1. New in 2013, similar to generic SSRIs, with more Nausea at 10x the cost
  3. Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
    1. Venlafaxine (Effexor)
    2. Same class as Tricyclic Antidepressants
  4. Norepinephrine Dopamine Reuptake Inhibitor (NDRI)
    1. Bupropion (Wellbutrin, Zyban)
  5. Serotonin Antagonist and Reuptake Inhibitor (SARI)
    1. Nefazodone (Serzone)
    2. Same class as Trazodone (Desyrel)
  6. Norepinephrine Antagonist Serotonin Antagonist (NASA)
    1. Mirtazapine (Remeron)

IX. Safety

  1. See Antidepressants in Lactation
  2. See Antidepressants in Pregnancy

X. References

  1. Bhatia (1997) Am Fam Physician 55(5):1683-94 [PubMed]
  2. Stone (2003) Am Fam Physician 68(3):498-504 [PubMed]

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