Which antidepressant is known not to worsen Periodic Limb Movement (PLM) index?

Antidepressants and Periodic Limb Movement Index

Bupropion is the antidepressant least likely to worsen periodic limb movement index and may actually reduce PLMS, making it the preferred antidepressant choice for patients with or at risk for periodic limb movements. 1, 2, 3

Relationship Between Antidepressants and PLMS

Periodic Limb Movement Disorder (PLMD) is characterized by repetitive, stereotyped limb movements during sleep that can cause sleep disturbance and daytime fatigue. The relationship between antidepressants and PLMS is important to understand:

• Most antidepressants, particularly SSRIs and tricyclics, are known to exacerbate PLMS 4, 5
• PLMS are common in patients taking antidepressants 4
• A PLMS Index exceeding 15 per hour is considered abnormal in adults 4

Evidence for Bupropion

Bupropion stands out as the antidepressant least likely to worsen PLMS:

• Bupropion SR has been shown to reduce objective measures of PLMD in depressed patients with the disorder 1
• In adolescents, bupropion showed only slightly increased indexes of non-periodic leg movements during sleep, while SSRIs significantly increased PLMS compared to controls 2
• When bupropion is administered in combination with SSRIs, it appears to counteract the SSRI-induced increase in PLMS, suggesting its dopaminergic effect outmatches the antidopaminergic action of SSRIs 2
• A randomized controlled trial demonstrated that bupropion did not exacerbate RLS symptoms and may even improve them 3

Other Antidepressants and Their Effects on PLMS

Several antidepressants have been associated with worsening PLMS:

• SSRIs (sertraline, fluoxetine, paroxetine, citalopram) have been shown to increase PLMS 5, 6
• Mirtazapine may be associated with higher rates of RLS and PLMS 5
• Venlafaxine may increase RLS symptoms and PLMS 5
• Tricyclic antidepressants like amitriptyline appear to increase PLMS that do not disrupt sleep 5

Some sedating antidepressants appear less problematic:

• Trazodone, nefazodone, and doxepin do not seem to aggravate PLMS 5

Clinical Approach for Patients with PLMS Requiring Antidepressant Therapy

1. First-line choice: Consider bupropion for patients with or at risk for PLMS

   • Starting dose: 150 mg sustained-release once daily 3
   • Monitor for 3-6 weeks for optimal effect 3

2. If bupropion is contraindicated or not tolerated:

   • Consider sedating antidepressants like trazodone, nefazodone, or doxepin 5
   • Avoid mirtazapine and venlafaxine which may have higher risk 5

3. If SSRIs must be used:

   • Monitor for emergence or worsening of PLMS
   • Consider combination with bupropion if PLMS develop, as it may counteract SSRI-induced PLMS 2

4. Additional considerations:

   • Check serum ferritin levels (values <50 ng/mL may contribute to PLMS) 4, 7
   • Consider iron supplementation if ferritin is low 7
   • Evaluate for other secondary causes of PLMS 7

Monitoring and Follow-up

• Assess for clinical sleep disturbance or daytime fatigue that may indicate clinically significant PLMS 4
• Consider polysomnography to document PLMS if symptoms suggest significant sleep disruption 4, 7
• Regular follow-up to assess symptom control and medication effectiveness 7

The dopaminergic properties of bupropion likely explain its favorable profile regarding PLMS, making it a rational choice for patients requiring antidepressant therapy who have or are at risk for PLMS.