What are the side effects of medications used to treat Obsessive-Compulsive Disorder (OCD), including Selective Serotonin Reuptake Inhibitors (SSRIs) like sertraline, fluoxetine, and paroxetine, and tricyclic antidepressants like clomipramine?

Side Effects of Medications for Obsessive-Compulsive Disorder (OCD)

Medications used to treat OCD commonly cause a range of side effects including gastrointestinal issues, sexual dysfunction, sleep disturbances, and rarely but importantly, increased suicidal thinking in young patients. 1

SSRI Side Effects (Sertraline, Fluoxetine, Paroxetine)

Common Side Effects

• Gastrointestinal symptoms:

  • Nausea (19-20%)
  • Dry mouth (10-11%)
  • Constipation (5-10%)
  • Diarrhea (9-11%)
  • Decreased appetite (5-6%)
  • Vomiting (3%)

• Nervous system effects:

  • Somnolence/drowsiness (15-16%)
  • Insomnia (11-12%)
  • Dizziness (6%)
  • Tremor (4-5%)
  • Headache
  • Nervousness (4%)

• Sexual dysfunction:

  • Abnormal ejaculation (13-28%)
  • Decreased libido (5-9%)
  • Impotence (5-9%)
  • Female genital disorders (5-9%)

• Other common effects:

  • Sweating (5-6%)
  • Fatigue/asthenia (12-14%)
  • Abnormal vision (3-4%)
  • Yawning (2-5%) 2, 1, 3

Dose-Dependent Side Effects

Side effects that increase with higher SSRI doses (which are typically required for OCD compared to depression):

• Dry mouth
• Sweating
• Constipation
• Somnolence
• Tremor
• Sexual dysfunction 3

Serious but Rare Side Effects

• Suicidal thinking and behavior (boxed warning for patients through age 24)
• Behavioral activation/agitation (restlessness, insomnia, impulsiveness, aggression)
• Hypomania/mania
• Serotonin syndrome
• Seizures
• Abnormal bleeding 2, 1

Clomipramine (Tricyclic Antidepressant) Side Effects

Common Side Effects

• Gastrointestinal:

  • Dry mouth (84%)
  • Constipation (47%)
  • Nausea (33%)
  • Dyspepsia (22%)
  • Anorexia (22%)

• Nervous system:

  • Somnolence (54%)
  • Tremor (54%)
  • Dizziness (54%)
  • Nervousness (52%)
  • Myoclonus (13%)

• Sexual dysfunction:

  • Ejaculation failure (42%)
  • Impotence (20%)
  • Changed libido

• Other:

  • Fatigue (39%)
  • Sweating (29%)
  • Weight gain
  • Visual changes (18%)
  • Myalgia (13%) 4

Serious Side Effects

• Cardiovascular effects (more common than with SSRIs):
  • QTc interval prolongation
  • Tachycardia
• Anticholinergic effects (much more pronounced than SSRIs)
• Higher risk of overdose toxicity compared to SSRIs 5, 6

Side Effect Comparison: SSRIs vs. Clomipramine

While clomipramine has similar efficacy to SSRIs in treating OCD, it has a significantly worse side effect profile:

• Higher discontinuation rates due to side effects (26% for clomipramine vs. 11% for sertraline) 7
• More pronounced anticholinergic effects (dry mouth, constipation)
• Greater cardiovascular risks
• Lower safety margin in overdose

This explains why SSRIs are generally preferred as first-line treatment despite comparable efficacy 6, 7.

Special Considerations

Children and Adolescents

• More vulnerable to behavioral activation/agitation with SSRIs
• Require closer monitoring for suicidal ideation
• May tolerate clomipramine poorly due to side effects 5, 8

Side Effect Management

• Most SSRI side effects emerge within the first few weeks of treatment
• Some side effects (nausea, dizziness) may diminish with continued therapy
• Others (dry mouth, somnolence, sexual dysfunction) may persist
• Slow dose titration can minimize initial side effects
• For persistent insomnia, short-term use of sleep aids may be considered 2, 1

Common Pitfalls

1. Premature discontinuation: Side effects often appear before therapeutic benefits, which may take 6-12 weeks
2. Inadequate dosing: Higher doses are typically required for OCD compared to depression or anxiety disorders
3. Abrupt discontinuation: Can lead to withdrawal symptoms; gradual tapering is recommended
4. Insufficient monitoring: Especially important during the first months of treatment and following dose adjustments 1

The side effect profile should be considered when selecting medication, with SSRIs generally offering better tolerability than clomipramine while maintaining similar efficacy in treating OCD.