Management of Sleep Disturbance in MDD with AUD History
Add mirtazapine to the current regimen rather than increasing Pristiq (desvenlafaxine). Mirtazapine specifically addresses the insomnia while maintaining depression treatment and poses no risk to alcohol use disorder remission, whereas higher doses of desvenlafaxine offer no additional efficacy and increase adverse effects.
Rationale for Adding Mirtazapine
Sleep-Specific Benefits
- Mirtazapine is specifically recommended for patients with both depression and insomnia due to its sedative properties, which directly target the frequent awakenings this patient is experiencing 1.
- The sedative effects are most beneficial when administered in the evening, allowing the medication to address nighttime sleep disturbances 1.
- Limited evidence shows similar efficacy among various antidepressants for treating depression with accompanying insomnia, but mirtazapine's sedating profile makes it particularly suited for augmentation in this clinical scenario 2.
Safety in Alcohol Use Disorder
- Mirtazapine has demonstrated effectiveness and tolerability specifically in patients with alcohol dependence and comorbid depressive disorders, with significant reductions in both mood symptoms and alcohol craving 3.
- In a multicentre study of alcohol-dependent patients with depression, mirtazapine reduced Hamilton Depression Rating Scale scores by 13.9 points and decreased alcohol craving scores by 42-53% 3.
- This is particularly important given the patient's history of AUD in remission, as mirtazapine does not appear to increase relapse risk 3.
Why Not Increase Pristiq
Desvenlafaxine shows no dose-response benefit above 50mg daily 4.
- FDA labeling explicitly states: "In studies directly comparing 50 mg per day and 100 mg per day there was no suggestion of a greater effect with the higher dose and adverse reactions and discontinuations were more frequent at higher doses" 4.
- The patient is already on 75mg, which exceeds the effective dose, making further increases unlikely to improve either depression or sleep 4.
- Higher doses of desvenlafaxine increase adverse effects without additional therapeutic benefit 4.
Practical Implementation
Dosing Strategy
- Start mirtazapine at 7.5-15mg at bedtime, as lower doses are often more sedating 5.
- Can titrate up to 30-45mg if needed for antidepressant augmentation, though sedation may paradoxically decrease at higher doses 5.
- Continue current Pristiq 75mg and naltrexone 50mg without modification 2.
Monitoring Considerations
- Common adverse effects include somnolence (54%), increased appetite (17%), and weight gain (12%) 5.
- Assess for improvement in sleep continuity within 1-2 weeks, as mirtazapine has a faster onset of action compared to other antidepressants 2.
- Monitor for any signs of alcohol craving or relapse, though mirtazapine has shown benefit in reducing craving 3.
Important Caveats
- Exercise caution if the patient has obstructive sleep apnea, as mirtazapine may worsen this condition 1.
- Naltrexone should be continued as it reduces relapse risk in alcohol use disorder, though it can cause hepatocellular injury and requires monitoring 2.
- Avoid benzodiazepines for sleep in this patient population due to abuse potential in individuals with AUD history 2.
Alternative Considerations if Mirtazapine Fails
- If mirtazapine is ineffective or not tolerated, consider switching (not augmenting) to a different antidepressant rather than increasing desvenlafaxine, as the STAR*D trial showed that switching medications resulted in remission in 25% of treatment-resistant patients 2.
- Sertraline combined with cognitive behavioral therapy has shown benefit in depressed alcoholics, though primarily for drinking outcomes rather than sleep 6.