What is the next best step for managing insomnia in a patient with alcohol use disorder and mild depression who has not responded to cognitive behavioral therapy?

Management of Insomnia in a Patient with Alcohol Use Disorder and Depression

Mirtazapine (option b) is the next best step for this patient, as it addresses both the insomnia and mild depression while avoiding the significant risks of benzodiazepines and Z-drugs in the context of active alcohol use disorder. 1, 2

Rationale for Mirtazapine Selection

In patients with comorbid insomnia and depression who have failed CBT-I, sedating antidepressants are the recommended third-line pharmacological approach after short-intermediate acting benzodiazepine receptor agonists. 1 However, the presence of moderate alcohol use disorder fundamentally changes this treatment algorithm.

Why Benzodiazepines and Z-Drugs Are Contraindicated

• Benzodiazepines (clonazepam, option a) and benzodiazepine receptor agonists (zolpidem option d, triazolam option c) should be avoided in patients with alcohol use disorder due to additive CNS depression, cross-tolerance with alcohol, and high risk of dependence and misuse. 1, 2

• The American Academy of Sleep Medicine explicitly warns about "additive effect on psychomotor performance with concomitant CNS depressants and/or alcohol use" and notes that "rapid dose decrease or abrupt discontinuance of benzodiazepines can produce withdrawal symptoms, including rebound insomnia, similar to that of barbiturates and alcohol." 1

• Benzodiazepines and GABA-A agonists should be avoided in patients with alcohol use disorder. 2

Evidence Supporting Mirtazapine

• Mirtazapine exhibits a moderate level of evidence for treating insomnia in patients with alcohol use disorder, making it one of the best-supported pharmacological options in this specific population. 2

• Mirtazapine addresses both the insomnia and the mild depression simultaneously, which is clinically advantageous since the American Academy of Sleep Medicine recommends sedating antidepressants "especially when used in conjunction with treating comorbid depression/anxiety." 1

• The recommended starting dose is 15 mg once daily, administered orally, preferably in the evening prior to sleep, with potential titration up to 45 mg per day if needed. 3

• Dose changes should not be made in intervals of less than 1 to 2 weeks to allow sufficient time for evaluation of response. 3

Alternative Considerations That Were Rejected

Zolpidem (option d)

• While zolpidem is typically a first-line agent for sleep-onset insomnia 1, 4, its use in active alcohol use disorder creates unacceptable risks of respiratory depression, cognitive impairment, and complex sleep behaviors when combined with alcohol. 1

Triazolam (option c)

• Triazolam is a short-acting benzodiazepine that carries all the risks of benzodiazepines in alcohol use disorder, including cross-tolerance, dependence, and dangerous interactions with alcohol. 1, 2

Clonazepam (option a)

• Clonazepam is a long-acting benzodiazepine with even greater risks than triazolam, including prolonged sedation, accumulation with repeated dosing, and severe withdrawal symptoms that mirror alcohol withdrawal. 1, 2

Critical Safety Monitoring

• Screen for bipolar disorder prior to initiating mirtazapine, as antidepressants can precipitate manic episodes in patients with undiagnosed bipolar disorder. 3

• Monitor for agranulocytosis: if the patient develops sore throat, fever, stomatitis, or other signs of infection along with low white blood cell count, discontinue mirtazapine immediately. 3

• Be vigilant for serotonin syndrome, particularly if the patient is taking other serotonergic medications. 3

• Counsel the patient that using alcohol to help fall asleep creates a higher risk of relapse, and continued alcohol use will undermine treatment effectiveness. 2

Common Pitfalls to Avoid

• Do not prescribe benzodiazepines or Z-drugs to patients with active substance use disorders, as this creates dangerous drug interactions and high potential for misuse. 1, 2

• Do not assume that standard insomnia treatment algorithms apply to patients with alcohol use disorder—the presence of active substance use fundamentally alters medication safety profiles. 2, 5

• Insomnia in alcohol use disorder may persist for weeks to months after initiating abstinence, so set realistic expectations about treatment timeline. 5, 6

• Do not discontinue mirtazapine abruptly; gradually reduce the dosage to avoid withdrawal symptoms. 3