Side Effects of Fluoxetine (SSRI) and Clomipramine (TCA)
Fluoxetine (SSRI) has fewer side effects than clomipramine (TCA), with the most common side effects including nausea, nervousness, insomnia, sexual dysfunction, and gastrointestinal disturbances, while clomipramine has a higher risk of cardiotoxic, hypotensive, and anticholinergic effects. 1, 2
Fluoxetine (SSRI) Side Effects
Common Side Effects
- Gastrointestinal disturbances (nausea, diarrhea) 1
- Insomnia or somnolence 1
- Nervousness and anxiety 2
- Sexual dysfunction 1
- Headache and dizziness 1
- Sweating 1
- Tremor 1
Serious Side Effects
- Serotonin syndrome (when combined with other serotonergic drugs) - symptoms include clonus, tremor, hyperreflexia, agitation, mental status changes, diaphoresis, and fever 1
- Risk of mania in patients with bipolar disorder 1
- Potential for SSRI withdrawal syndrome with sudden cessation 1
- Possible increased risk of suicidal ideation in adolescents (but not significantly in adults) 1
- Potential QT interval prolongation at high doses 3
- Seizures (rare, primarily at very high doses) 3, 2
Special Considerations
- Long half-life - side effects may not manifest for a few weeks 1
- Activating effects - may increase energy levels 1
- May interact with warfarin, increasing bleeding risk 3
- Generally well tolerated in overdose compared to TCAs 2
- Pregnancy considerations: potential risk for persistent pulmonary hypertension of the newborn when used after 20th week of gestation 3
Clomipramine (TCA) Side Effects
Common Side Effects
- Anticholinergic effects (dry mouth, constipation, urinary retention) 1
- Sedation 1
- Cardiotoxic effects (tachycardia, arrhythmias) 1
- Hypotension 1
- Sexual dysfunction 1
- Weight gain 1
Serious Side Effects
- Higher risk of cardiotoxicity compared to SSRIs 1
- Greater risk of seizures compared to SSRIs 1
- More dangerous in overdose than SSRIs 3
- Potential for significant drug interactions, especially with SSRIs 4
Comparison Between Fluoxetine and Clomipramine
Efficacy vs. Side Effects
- Clomipramine may have somewhat larger therapeutic effect in OCD but with more side effects 5
- SSRIs like fluoxetine are generally favored over clomipramine due to better side effect profile 1
- Fluoxetine has fewer anticholinergic side effects than clomipramine 2
Drug Interactions
- Combining fluoxetine and clomipramine can lead to dangerous metabolic interactions, resulting in subtoxic concentrations of clomipramine 4
- Both medications can contribute to serotonin syndrome when combined with other serotonergic agents 1, 6
Important Warnings and Precautions
- Never combine fluoxetine and clomipramine without careful monitoring as this can lead to dangerous elevations in clomipramine levels 4, 7
- Avoid abrupt discontinuation of either medication to prevent withdrawal symptoms 1
- Monitor for signs of serotonin syndrome when using either medication, especially in combination with other serotonergic drugs 1
- Both medications should be used with caution in patients with a history of seizures 3
- Fluoxetine should be avoided in patients with bipolar disorder due to risk of mania 1
- Careful dosing and monitoring is required in elderly patients for both medications 1