What are alternative antidepressants to bupropion (Wellbutrin) that do not cause constipation?

Alternative Antidepressants to Bupropion That Do Not Cause Constipation

Mirtazapine is the best alternative to bupropion for patients concerned about constipation, as it has the lowest gastrointestinal side effect profile among commonly used antidepressants and is not associated with constipation. 1

Understanding Antidepressant-Related Constipation

While bupropion is generally considered to have a favorable side effect profile, constipation can occur with this medication. 2, 3 In fact, a case report documented severe constipation requiring hemorrhoidectomy surgery in a patient taking extended-release bupropion, which resolved after discontinuation. 4

Anticholinergic drugs, including many antidepressants, are known to cause constipation, particularly tricyclic antidepressants (TCAs) which have significant anticholinergic effects. 2

Best Alternative: Mirtazapine

Mirtazapine stands out as having the fewest gastrointestinal side effects among second-generation antidepressants, with the only notable GI effect being increased appetite rather than constipation. 1

Key Advantages of Mirtazapine:

• Not associated with constipation in systematic reviews of gastrointestinal side effects 1
• Effective for depression with significant improvement in symptoms within 1-2 weeks of treatment 5
• Unique mechanism: Enhances norepinephrine and serotonin neurotransmission by blocking alpha-2 presynaptic adrenoceptors 5
• Dosing: 15-45 mg once daily at bedtime 5

Important Considerations:

• Most common side effect is sedation, which can be beneficial for patients with insomnia but may be problematic for others 5
• Weight gain and increased appetite are notable side effects 5
• Transient elevations in cholesterol and liver function tests may occur 5

Other Reasonable Alternatives

SSRIs (Use with Caution)

While SSRIs are effective antidepressants, escitalopram and sertraline are associated with the highest rates of gastrointestinal side effects, including nausea, vomiting, and diarrhea, though they are less commonly associated with constipation compared to TCAs. 1

SSRIs showed only possible improvement in symptom relief for IBS and did not significantly improve global symptoms, with low certainty of evidence. 2 However, they are not specifically associated with high rates of constipation. 1

Vortioxetine

Vortioxetine is a novel antidepressant with multimodal activity including serotonin transporter inhibition and various 5-HT receptor modulation. 5

• Most common adverse effects: Nausea, sexual dysfunction, constipation, and vomiting 5
• Note: Constipation is listed as a side effect, making it less ideal than mirtazapine 5
• Dosing: Maximum 20 mg daily, with improvement at 2 weeks and full effect at 4-6 weeks 5

Vilazodone

Vilazodone is an SSRI with 5-HT1A receptor partial agonist activity, offering potentially reduced sexual side effects compared to traditional SSRIs. 5

• Most common adverse effects: Diarrhea, nausea, vomiting, and insomnia (notably, constipation is not listed as a primary side effect) 5
• Dosing: 40 mg daily with improvement within 1 week 5

Antidepressants to Avoid for Constipation

Tricyclic Antidepressants (TCAs)

TCAs should be avoided or used with extreme caution in patients concerned about constipation due to their significant anticholinergic effects. 2

• Secondary amine TCAs (desipramine, nortriptyline) have lower anticholinergic effects than tertiary amines and may be better tolerated, but still cause constipation 2
• TCAs are known constipating medications that should be discontinued when possible in patients with existing constipation 2

Clinical Algorithm for Selection

When choosing an antidepressant for a patient concerned about constipation:

1. First-line choice: Mirtazapine - if sedation and potential weight gain are acceptable 1, 5

2. Second-line choice: Vilazodone - if activating properties are preferred and diarrhea risk is acceptable 5

3. Consider SSRIs (fluoxetine, citalopram) - if neither sedation nor activation is specifically needed, though nausea may be problematic 1

4. Avoid: TCAs, and use caution with vortioxetine which lists constipation as a side effect 2, 5

Critical Monitoring

For any antidepressant initiated:

• Monitor for suicidal ideation, especially in patients under 24 years, particularly during the first 1-2 months 2
• Allow 6-8 weeks at therapeutic doses before determining treatment response 2
• Assess gastrointestinal symptoms at each follow-up visit 2