Can trazodone (antidepressant medication) cause bone pain?

Trazodone and Bone Pain

Trazodone is not typically associated with bone pain as a side effect, and there is no substantial evidence in clinical guidelines linking trazodone to bone pain. 1

Understanding Trazodone's Side Effect Profile

Trazodone is a serotonin receptor antagonist and reuptake inhibitor (SARI) antidepressant used for treating major depressive disorder and off-label for insomnia. Its common side effect profile includes:

• Drowsiness/sedation (most common)
• Headache
• Dizziness
• Dry mouth
• Orthostatic hypotension (particularly in elderly patients)
• Minimal anticholinergic activity
• QT interval prolongation (rare)
• Cardiac arrhythmias (rare)
• Priapism (rare) 2

The National Comprehensive Cancer Network guidelines and other authoritative sources do not list bone pain among trazodone's known side effects 3, 1.

Potential Mechanisms for Pain Related to Trazodone

While bone pain specifically is not documented, there are some potential mechanisms that could theoretically cause pain in patients taking trazodone:

1. Referred pain: Trazodone's alpha-adrenergic blocking properties can cause priapism, which might manifest as referred pain to the flank region 1

2. Serotonergic effects: Medications affecting serotonin pathways can influence renal function, potentially manifesting as flank pain, though this is not specifically documented for trazodone 1

Differential Diagnosis for Bone Pain in Patients on Trazodone

If a patient on trazodone reports bone pain, consider these more likely causes:

• Musculoskeletal disorders (common in older adults) 3
• Cancer-related bone pain (if relevant) 3
• Osteoporotic fractures
• Inflammatory conditions
• Other medications the patient may be taking

Management Approach

If a patient on trazodone presents with bone pain:

1. Rule out common causes of bone/musculoskeletal pain first 1
2. Consider timing of pain onset in relation to trazodone initiation
3. Evaluate for other symptoms that might suggest alternative diagnoses
4. If trazodone is suspected as the cause and the clinical situation allows, consider a trial of discontinuation to see if symptoms resolve 1
5. Consider alternative medications for depression or insomnia if needed:
   • SSRIs
   • SNRIs
   • Other SARIs 1

Treatment Options for Bone Pain

For management of bone pain (regardless of cause):

• NSAIDs, acetaminophen, or steroids may improve bone pain control 3
• Topical diclofenac (gel or patch) may provide relief with minimal systemic effects 3
• For severe cases, consider consultation with pain specialists 3
• Physical and occupational therapy may be beneficial 3

Important Considerations

• Trazodone has a relatively safer profile in overdose compared to tricyclic antidepressants 2
• It has fewer anticholinergic and cardiovascular side effects than older antidepressants 4
• Maximum tolerated doses in elderly patients are 300-400 mg/day 4
• The prolonged-release formulation may provide improved tolerability 2

If bone pain persists after ruling out common causes and considering trazodone's role, further investigation for underlying conditions is warranted, as bone pain is more likely related to other medical conditions than to trazodone use.