Trazodone Safety in Parkinson's Disease
Trazodone can be used cautiously in Parkinson's disease patients for sleep disturbances, but it carries significant risks including worsening motor function and potential drug-induced parkinsonism that must be carefully weighed against benefits.
Key Safety Considerations
Motor Function Risks
- Trazodone can worsen parkinsonian motor symptoms and reduce the duration of L-DOPA's anti-parkinsonian effect by approximately 21%. 1
- Case reports document reversible trazodone-induced parkinsonism in patients without pre-existing PD, with symptoms including bilateral cogwheel rigidity, shuffling gait, tremors, and falls that resolved within one week of discontinuation. 2, 3
- In parkinsonian marmoset models, trazodone 10 mg/kg significantly worsened parkinsonian disability despite reducing dyskinesia. 1
Cardiovascular and Other Risks
- Trazodone carries risks of orthostatic hypotension and cardiac arrhythmias, which are particularly concerning given that PD patients frequently experience autonomic dysfunction including baseline orthostatic hypotension. 4, 5
- The American Geriatrics Society Beers Criteria does not specifically list trazodone, though it warns about sedating medications in older adults with neurodegenerative disease. 4
- Trazodone requires caution in patients with premature ventricular contractions. 5
Evidence for Efficacy in PD Sleep Disorders
Comparative Trial Data
- A 2022 randomized, double-blind trial in PD patients demonstrated that trazodone 50 mg/day was effective and tolerable for improving sleep quality, with efficacy comparable to melatonin 3 mg/day and clonazepam 1 mg/day. 6
- Trazodone showed superior reduction in daytime sleepiness (ESS scores) compared to clonazepam, though melatonin was superior for REM sleep behavior disorder symptoms. 6
- Mild adverse events occurred in 2 patients in the trazodone group versus 3 in the clonazepam group and none with melatonin. 6
Potential Benefits
- In animal models, trazodone reduced L-DOPA-induced dyskinesia by approximately 39% and psychosis-like behaviors by 17%, though this came at the cost of worsened motor function. 1
- Trazodone has minimal anticholinergic activity compared to tricyclic antidepressants, potentially making it better tolerated in elderly PD patients. 5
Clinical Recommendations
When to Consider Trazodone
- Use trazodone only when first-line agents (melatonin, clonazepam) are contraindicated, ineffective, or not tolerated. 6
- Consider for PD patients with insomnia who also have significant daytime sleepiness that might benefit from trazodone's effects. 6
- May be considered as an alternative to antipsychotics for agitation in PD dementia at doses of 25-200 mg/day in divided doses. 5
Dosing and Monitoring
- Start with low doses (25-50 mg at bedtime) and monitor closely for worsening motor symptoms, falls, and orthostatic hypotension. 5, 6
- Assess for drug interactions, particularly with medications that inhibit trazodone metabolism (e.g., amiodarone), which can increase adverse effects. 3
- Monitor for excessive daytime sedation, gait instability, and falls during initial treatment. 7
Critical Contraindications and Warnings
- Avoid in PD patients with significant baseline motor instability, frequent falls, or severe orthostatic hypotension. 4, 3
- Discontinue immediately if new or worsening parkinsonian symptoms develop (tremor, rigidity, shuffling gait, falls). 2, 3
- Exercise extreme caution in patients with cardiac conduction abnormalities or those taking QT-prolonging medications. 5
Preferred Alternatives
First-Line Options for Sleep in PD
- Melatonin 3-15 mg at bedtime is preferred as first-line therapy for sleep disturbances in PD, with fewer side effects and specific benefits for REM sleep behavior disorder. 4, 6
- Clonazepam 0.25-1 mg remains an option but is listed on the Beers Criteria as potentially inappropriate in older adults. 4
For Psychosis in PD
- Quetiapine, clozapine, and pimavanserin are the recognized exceptions for antipsychotic use in PD, not trazodone. 4