In a patient with obsessive‑compulsive disorder on an SSRI who has insomnia, mood, and anxiety symptoms, can trazodone be used to improve sleep and mood/anxiety and also treat OCD?

Trazodone for Sleep, Mood, Anxiety, and OCD: Evidence-Based Recommendations

Trazodone should NOT be used for OCD treatment, as it lacks efficacy for this condition, and major guidelines explicitly recommend against its use for insomnia despite its common off-label prescription. 1, 2

Critical Evidence Against Trazodone for OCD

• Trazodone does not appear effective for obsessive-compulsive disorder, in direct contrast to fluoxetine and other SSRIs that demonstrate clear efficacy for OCD. 2

• The mechanism explains this failure: trazodone's primary action is 5-HT2A/2C receptor antagonism rather than serotonin reuptake inhibition, which is the mechanism required for OCD treatment. 2

• While fluoxetine (a pure SSRI) effectively treats OCD through serotonin uptake inhibition, trazodone's antagonist action at serotonin receptors does not produce anti-obsessional effects. 2

Trazodone for Insomnia: Strong Recommendations Against Use

Guideline Position

• The American Academy of Sleep Medicine and VA/DOD guidelines explicitly recommend AGAINST using trazodone for chronic insomnia because the low-quality evidence of modest benefit is outweighed by its adverse-effect profile. 1, 3

• Systematic reviews found no significant differences between trazodone (50-150 mg) and placebo for objective sleep measures including sleep efficiency, sleep-onset latency, total sleep time, or wake after sleep onset. 1

• Only modest subjective sleep quality improvement was noted, which guideline panels judged insufficient to justify use given safety concerns. 1

Why Trazodone Became Popular Despite Lack of Evidence

• From 1987-1996, trazodone prescriptions for insomnia increased nearly 150% as physicians sought to avoid benzodiazepine dependency concerns, despite the complete absence of efficacy studies for insomnia at that time. 4

• Trazodone remains the second most commonly prescribed sleep medication in the United States purely through off-label use, not evidence-based practice. 5

Trazodone for Mood and Anxiety: Limited Role

Depression Treatment

• For major depressive disorder, trazodone requires doses of 150-300 mg daily to achieve antidepressant effects—far higher than the 25-50 mg typically used for sleep. 1, 6

• At the low doses used for insomnia (25-50 mg), trazodone provides no meaningful antidepressant activity. 1

• Trazodone demonstrates comparable antidepressant efficacy to SSRIs and SNRIs when used at therapeutic antidepressant doses. 6

Anxiety Disorders

• While some evidence supports trazodone use for generalized anxiety disorder, it does NOT effectively treat panic disorder, similar to its failure in OCD. 7, 2

• The off-label use for anxiety disorders lacks the robust clinical trial evidence available for SSRIs. 7, 8

Evidence-Based Treatment Algorithm for Your Patient

For OCD (Primary Concern)

• Continue and optimize the current SSRI (increase to maximum therapeutic dose if not already there) as this is the evidence-based treatment for OCD. 2

• Consider switching to a different SSRI or clomipramine if the current SSRI fails at maximum dose. 2

• Do NOT add trazodone expecting any benefit for OCD symptoms. 2

For Insomnia (First-Line to Third-Line)

1. Cognitive Behavioral Therapy for Insomnia (CBT-I) MUST be offered first before any medication, as it demonstrates superior long-term efficacy with sustained benefits after discontinuation. 1

2. Second-line FDA-approved options (if CBT-I insufficient):

   • Eszopiclone 2-3 mg for sleep onset and maintenance 1
   • Zolpidem 10 mg for sleep onset and maintenance 1
   • Ramelteon 8 mg for sleep onset (preferred if substance-use history due to zero addiction potential) 1
   • Low-dose doxepin 3-6 mg for sleep maintenance (most effective for maintenance, minimal side effects, no abuse potential) 1

3. Trazodone should only be considered as a third-line agent after FDA-approved options have failed AND when comorbid depression requiring full antidepressant dosing is present. 1

For Mood/Anxiety Symptoms

• If depressive symptoms are prominent and require treatment, use therapeutic antidepressant doses of the SSRI already prescribed for OCD (typically 40-80 mg fluoxetine equivalent), which will simultaneously treat depression, anxiety, and OCD. 2

• If insomnia persists despite optimized SSRI therapy, add low-dose doxepin 3-6 mg rather than trazodone, as it has superior evidence for sleep maintenance with minimal side effects. 1

Critical Safety Concerns with Trazodone

• Daytime drowsiness, dizziness, and psychomotor impairment are common, particularly problematic in older adults. 1

• Orthostatic hypotension occurs frequently, especially in elderly patients or those with heart disease. 6

• Priapism is a rare but serious adverse effect requiring immediate emergency care if erection lasts >4 hours. 1

• Additive CNS depression occurs when combined with other sedatives, opioids, or alcohol. 1

Common Clinical Pitfalls to Avoid

• Do not prescribe trazodone expecting it to treat OCD—the mechanism of action is wrong and clinical evidence shows no efficacy. 2

• Do not use low-dose trazodone (25-50 mg) expecting antidepressant effects—these doses are subtherapeutic for mood disorders. 1

• Do not prescribe trazodone as first-line for insomnia—guidelines explicitly recommend against this practice. 1

• Do not combine trazodone with benzodiazepines or other sedatives without clear justification and close monitoring due to additive sedation and respiratory depression risk. 1

• Do not assume trazodone is "safer" than FDA-approved hypnotics—evidence does not support a superior safety profile. 1