What are the side effects of each Selective Serotonin Reuptake Inhibitor (SSRI)?

Side Effects of Selective Serotonin Reuptake Inhibitors (SSRIs)

Each SSRI has a distinct side effect profile, with paroxetine having the highest rate of sexual dysfunction, sertraline causing more diarrhea, and escitalopram having the least drug interactions and QT prolongation concerns at therapeutic doses.

Common Side Effects Across All SSRIs

All SSRIs share several common side effects, though their frequency and severity may differ:

• Gastrointestinal effects: Nausea, vomiting, diarrhea, constipation 1
• Neurological effects: Headache, dizziness, tremors, paresthesia 1, 2
• Sleep disturbances: Insomnia or somnolence 1, 3
• Sexual dysfunction: Erectile dysfunction, delayed ejaculation, anorgasmia, decreased libido 1, 4
• Weight changes: Primarily weight gain with long-term use 2, 3
• Behavioral activation/agitation: More common in children and early in treatment 1

Studies indicate approximately 86% of patients experience at least one side effect, with 55% reporting at least one bothersome side effect 3. Most side effects emerge within the first two weeks but often persist throughout treatment 3.

SSRI-Specific Side Effect Profiles

Fluoxetine

• Distinctive features:
  • More activating/energizing than other SSRIs
  • Long half-life (reduces discontinuation symptoms)
  • Higher risk of drug interactions due to CYP450 inhibition 5, 2
• Specific concerns:
  • Potential for neonatal complications when used during pregnancy 5
  • May cause weight loss initially, but potential for weight gain with long-term use

Sertraline

• Distinctive features:
  • Highest incidence of diarrhea among SSRIs 1
  • More psychiatric symptoms reported compared to other SSRIs 6
  • Moderate effect on CYP450 enzymes
• Specific concerns:
  • Lower rate of sexual dysfunction than paroxetine but higher than bupropion 1

Paroxetine

• Distinctive features:
  • Highest rate of sexual dysfunction among SSRIs 1, 4
  • Highest risk of discontinuation syndrome due to short half-life 1
  • Higher risk of weight gain compared to other SSRIs 1
• Specific concerns:
  • Associated with increased risk of suicidal thinking compared to other SSRIs 1
  • Strong anticholinergic effects (dry mouth, constipation, blurred vision)

Escitalopram

• Distinctive features:
  • Least effect on CYP450 isoenzymes (fewer drug interactions) 4
  • Better tolerated overall with fewer side effects
• Specific concerns:
  • QT prolongation risk at doses exceeding 40mg/day 1, 4
  • Should be used with caution in patients with congenital long QT syndrome 7

Citalopram

• Distinctive features:
  • QT prolongation risk at doses exceeding 40mg/day 1
  • Moderate drug interaction potential
• Specific concerns:
  • FDA warning about cardiac effects at higher doses
  • Should be avoided in patients with long QT syndrome 1

Fluvoxamine

• Distinctive features:
  • Higher incidence of gastrointestinal symptoms 6
  • Significant risk of discontinuation syndrome 1
• Specific concerns:
  • Greatest potential for drug-drug interactions among SSRIs 1
  • More sedating than other SSRIs

Severe Adverse Events

Serotonin Syndrome

• Potentially life-threatening condition caused by excessive serotonergic activity
• Symptoms: Confusion, agitation, hyperthermia, hyperreflexia, tremor, diarrhea, autonomic instability
• Risk increases when combining SSRIs with other serotonergic medications, especially MAOIs 1

Bleeding Risk

• SSRIs increase bleeding risk, especially when combined with NSAIDs or aspirin
• Manifestations range from ecchymoses and epistaxis to life-threatening hemorrhages 1, 7

Suicidality

• Increased risk of suicidal thinking and behavior, particularly in children, adolescents, and young adults
• Close monitoring recommended by FDA, especially during first months of treatment 1

Hyponatremia

• More common in elderly patients
• Symptoms include confusion, headache, fatigue, seizures 6

Discontinuation Syndrome

• Symptoms: Dizziness, sensory disturbances, anxiety, irritability, nausea
• More common with paroxetine, fluvoxamine, and sertraline 1
• Less common with fluoxetine due to its long half-life

Management of Side Effects

1. Sexual dysfunction:

   • Consider dose reduction
   • Drug holidays (for weekend sexual activity)
   • Switch to medications with fewer sexual side effects (bupropion) 4

2. Gastrointestinal effects:

   • Take medication with food
   • Gradual dose titration
   • Temporary use of antacids 4

3. Sleep disturbances:

   • Adjust timing of medication (morning for activating effects, evening for sedating effects)
   • Consider short-term sleep aids if needed 4

4. Weight gain:

   • Regular monitoring of weight
   • Dietary counseling and exercise recommendations 4

Special Considerations

• Elderly patients: Start with lower doses due to increased risk of side effects, especially hyponatremia and falls 4
• Pregnancy: Fluoxetine has demonstrated relative safety, but risk of neonatal complications exists 5
• Hepatic/renal impairment: Dose adjustments required, especially for escitalopram 4, 7
• Drug interactions: Caution when combining with medications affecting bleeding risk or serotonergic activity 1, 7

Most side effects are dose-dependent and may improve with time or dose adjustment. However, sexual dysfunction and weight gain often persist throughout treatment 3.