What is the order of side effects of Selective Serotonin Reuptake Inhibitors (SSRIs) from most common to least common?

Order of Side Effects of SSRIs from Most Common to Least Common

The most common side effects of SSRIs are nausea/vomiting, followed by sexual dysfunction, insomnia, diarrhea, headache, dizziness, somnolence, dry mouth, fatigue, decreased appetite, and sweating. 1

Most Common Side Effects (>10% incidence)

1. Nausea and vomiting: Approximately 15-18% of patients experience nausea, making it the most common side effect of SSRIs and the most common reason for discontinuation 1, 2

2. Sexual dysfunction: 12-17% of patients report sexual side effects including:

   • Ejaculatory delay (most common in males - 9-14%)
   • Decreased libido (6% in males, 3% in females)
   • Anorgasmia (3% in females)
   • Impotence (2-3% in males) 2, 3

3. Insomnia: 9-12% of patients experience sleep disturbances 2

Common Side Effects (5-10% incidence)

1. Diarrhea: 8% of patients report this gastrointestinal side effect 1, 2

2. Headache: 5-7% of patients experience headaches 1

3. Dizziness: 5% of patients report dizziness 1, 2

4. Somnolence/drowsiness: 6-13% of patients experience drowsiness or fatigue 1, 2

5. Dry mouth: Reported in approximately 3-9% of patients 1, 2

Less Common Side Effects (<5% incidence)

1. Fatigue: 5-8% of patients report fatigue 1, 2

2. Decreased appetite: 3% of patients experience reduced appetite 1, 2

3. Sweating: 3-8% of patients report increased sweating 1, 2

4. Constipation: 3-5% of patients experience constipation 1, 2

5. Weight changes: Weight gain is reported in real-world settings more frequently than in clinical trials 4

6. Tremor: Reported in approximately 2-3% of patients 1

Serious but Rare Side Effects

• Serotonin syndrome: Characterized by tremor, diarrhea, delirium, neuromuscular rigidity, and hyperthermia. Occurs in 14-16% of SSRI overdoses but is rare with normal dosing 1

• Suicidality: Increased risk of suicidal thinking and behavior, particularly in young adults under 24 years 1

• Behavioral activation/agitation: More common in younger patients and those with anxiety disorders 1

• Bleeding abnormalities: Especially when combined with NSAIDs or aspirin 1

• Hyponatremia: More common in elderly patients 1

Important Clinical Considerations

• Side effects typically emerge within the first few weeks of treatment, with most appearing in the first 2 weeks 5

• Contrary to expectations, most side effects (particularly sexual dysfunction and vision problems) persist during the first 3 months of treatment rather than resolving 5

• Physicians tend to significantly underestimate both the occurrence and bothersomeness of SSRI side effects 5

• Only about 40% of patients report side effects to their physicians, despite 55% experiencing at least one bothersome side effect 5, 4

• Different SSRIs have slightly different side effect profiles:

  • Sertraline has a higher rate of diarrhea than other SSRIs
  • Paroxetine has higher rates of sexual dysfunction and weight gain
  • Fluoxetine and paroxetine should generally be avoided in older adults due to higher rates of adverse effects 1

Medication Selection Algorithm

1. For most patients, sertraline is recommended as first-line due to favorable efficacy and tolerability 6

2. For patients concerned about sexual dysfunction, consider bupropion which has significantly lower rates of sexual side effects 1

3. For elderly patients, preferred agents include citalopram, escitalopram, and sertraline; avoid paroxetine and fluoxetine 1

4. For patients with insomnia, avoid activating SSRIs like fluoxetine; consider more sedating options 1

5. For patients with gastrointestinal concerns, escitalopram may have a more favorable profile than sertraline 2

Remember that approximately 63% of patients on SSRIs will experience at least one side effect, but the benefits in treating depression and anxiety often outweigh these risks 1.