What medication is recommended for a patient with anxiety and insomnia, considering potential substance abuse history and elderly patients?

Medication for Anxiety and Insomnia

First-Line Treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I)

All patients with chronic insomnia and anxiety should receive Cognitive Behavioral Therapy for Insomnia (CBT-I) as initial treatment before or alongside any pharmacotherapy, as it demonstrates superior long-term efficacy with sustained benefits and minimal adverse effects. 1

• CBT-I includes stimulus control therapy, sleep restriction therapy, relaxation techniques, and cognitive restructuring of negative thoughts about sleep 1
• CBT-I can be delivered through individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats show effectiveness 1
• Behavioral interventions provide longer-term sustained benefit compared to medications, which only offer short-term relief 1

Pharmacological Treatment Algorithm

For Patients with Comorbid Anxiety and Depression

Sedating antidepressants are the preferred initial pharmacological choice when comorbid depression or anxiety is present, as they simultaneously address both the mood disorder and sleep disturbance. 1

• Low-dose doxepin (3-6 mg) is specifically recommended for sleep maintenance insomnia with high-strength evidence showing improvement in sleep latency, total sleep time, and sleep quality 1
• Mirtazapine may be considered for patients with comorbid depression/anxiety, though it must be taken nightly on a scheduled basis (not PRN) due to its 20-40 hour half-life 1
• Trazodone is explicitly NOT recommended despite widespread off-label use, as the American Academy of Sleep Medicine advises against it for insomnia due to limited efficacy evidence and significant adverse effect profile 1

For Patients WITHOUT Comorbid Depression

Short-intermediate acting benzodiazepine receptor agonists (BzRAs) or ramelteon are first-line medications when sedating antidepressants are not indicated. 1

First-line options include:

• Eszopiclone 2-3 mg for both sleep onset and sleep maintenance insomnia 1
• Zolpidem 10 mg (5 mg in elderly) for both sleep onset and sleep maintenance 1
• Zaleplon 10 mg for sleep onset insomnia only 1
• Ramelteon 8 mg for sleep onset insomnia, particularly advantageous as it has no abuse potential 1, 2

Second-line options if first-line fails:

• Suvorexant (orexin receptor antagonist) for sleep maintenance insomnia 1
• Temazepam 15 mg for both sleep onset and maintenance 1

Special Considerations for Patients with Substance Abuse History

For patients with a history of substance abuse, avoid benzodiazepines and consider ramelteon or suvorexant as preferred agents. 1

• Ramelteon showed no differences in subjective responses indicative of abuse potential compared to placebo at doses up to 20 times the recommended therapeutic dose in subjects with a history of sedative/hypnotic abuse 2
• Ramelteon has no withdrawal potential or rebound insomnia after discontinuation 2
• Benzodiazepines carry significant risks of dependence and withdrawal reactions 1

Special Considerations for Elderly Patients

Low-dose doxepin (3-6 mg) is the first-choice pharmacological agent for elderly patients, offering the best balance of efficacy and safety with fewer adverse effects than other sleep medications. 3, 4

• Start at the lowest available dose (3 mg) due to altered pharmacokinetics and increased sensitivity to side effects 3, 4
• Doxepin does not carry black box warnings or significant safety concerns associated with benzodiazepines and Z-drugs 3

Alternative options for elderly patients if doxepin fails:

• Ramelteon 8 mg for difficulty falling asleep, with minimal adverse effects and no dependency risk 3, 2
• Suvorexant (start at 10 mg in elderly) for sleep maintenance with only mild side effects 3
• Eszopiclone 1-2 mg (reduced dose) for combined sleep-onset and maintenance problems 3
• Zaleplon 5 mg (reduced dose) for sleep-onset insomnia only 3
• Zolpidem 5 mg maximum (NOT 10 mg) for elderly patients due to increased sensitivity 1, 3

Medications to AVOID in elderly patients:

• All benzodiazepines (including temazepam, diazepam, lorazepam, clonazepam, triazolam) due to unacceptable risks of dependency, falls, cognitive impairment, respiratory depression, and increased dementia risk 3, 4
• Over-the-counter antihistamines (diphenhydramine, chlorpheniramine) due to strong anticholinergic effects including confusion, urinary retention, fall risk, and delirium 3, 4
• Trazodone despite widespread off-label use 3, 4
• Barbiturates and chloral hydrate are absolutely contraindicated 3

Critical Safety Considerations

• All hypnotics carry risks including daytime impairment, complex sleep behaviors (sleep-driving, sleep-walking), falls, fractures, and cognitive impairment, particularly in elderly patients 1
• Use the lowest effective dose for the shortest duration possible, typically less than 4 weeks for acute insomnia 1
• Monitor patients regularly to assess effectiveness and side effects, especially during the initial treatment period 1
• Pharmacotherapy should supplement, not replace, CBT-I 1

Common Pitfalls to Avoid

• Failing to implement CBT-I before or alongside medication, as behavioral interventions provide more sustained effects than medication alone 1
• Using benzodiazepines like lorazepam as first-line treatment for insomnia 1
• Continuing pharmacotherapy long-term without periodic reassessment 1
• Using over-the-counter sleep aids or herbal supplements with limited efficacy data 1
• Prescribing standard adult doses to elderly patients without age-adjusted dosing 1, 3