What are the guidelines for prescribing medication to a patient with insomnia, considering their medical history and potential for substance abuse or dependence?

Insomnia Medication Prescribing Guidelines

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

All patients with chronic insomnia must receive CBT-I as the initial treatment before or alongside any pharmacotherapy, as it demonstrates superior long-term efficacy compared to medications with sustained benefits after discontinuation. 1, 2, 3

• CBT-I includes stimulus control therapy (going to bed only when sleepy, using bed only for sleep/sex), sleep restriction therapy (limiting time in bed to actual sleep time), relaxation techniques, and cognitive restructuring of negative thoughts about sleep 1, 2, 3
• CBT-I can be delivered through individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats show effectiveness 2, 3
• Sleep hygiene education alone is insufficient as monotherapy but should supplement other CBT-I components: avoiding caffeine/alcohol in evening, maintaining consistent sleep-wake times, limiting daytime naps to 30 minutes before 2 PM 2, 3
• Improvements from CBT-I are gradual but durable beyond treatment end, with initial mild sleepiness and fatigue typically resolving quickly 2

First-Line Pharmacotherapy Algorithm

When pharmacotherapy is necessary (after CBT-I initiation or for patients unable to participate in CBT-I), prescribe short-intermediate acting benzodiazepine receptor agonists (BzRAs) or ramelteon as first-line agents. 1, 2, 3

For Sleep Onset Insomnia:

• Zaleplon 10 mg (5 mg in elderly): very short half-life, minimal residual sedation, take only when able to sleep 4+ hours 2, 3
• Zolpidem 10 mg (5 mg in elderly/women): effective for both onset and maintenance, take on empty stomach 2, 3, 4
• Ramelteon 8 mg: melatonin receptor agonist, zero addiction potential, no DEA scheduling, preferred for patients with substance use history 2, 3
• Triazolam 0.25 mg: associated with rebound anxiety, not considered first-line 2

For Sleep Maintenance Insomnia:

• Eszopiclone 2-3 mg: effective for both onset and maintenance, longer duration of action 2, 3, 5
• Zolpidem 10 mg (5 mg in elderly/women): addresses both onset and maintenance 2, 3, 4
• Temazepam 15 mg: traditional benzodiazepine option, higher risk profile than non-benzodiazepines 2, 3
• Low-dose doxepin 3-6 mg: reduces wake after sleep onset by 22-23 minutes, minimal anticholinergic effects at this dose, no weight gain 2, 3
• Suvorexant: orexin receptor antagonist, reduces wake after sleep onset by 16-28 minutes 2, 3

Second-Line Options

If initial BzRAs or ramelteon fail, try an alternate agent from the same class before moving to other drug categories. 1, 2, 3

Sedating Antidepressants (Third-Line):

• Use when comorbid depression/anxiety is present 1, 2, 3
• Trazodone: NOT recommended by AASM due to insufficient efficacy data and harms outweighing benefits 2, 3
• Mirtazapine: requires nightly scheduled dosing (not PRN), half-life 20-40 hours, appropriate for comorbid depression 2
• Amitriptyline: sedating but significant anticholinergic burden 1
• Low-dose doxepin 3-6 mg: specifically for sleep maintenance, different from higher antidepressant doses 2, 3

Combined BzRA or Ramelteon Plus Sedating Antidepressant:

• Consider when monotherapy insufficient and comorbid mood disorder present 1

Other Sedating Agents (Fourth-Line):

• Anti-epilepsy medications (gabapentin, tiagabine): tiagabine NOT recommended by AASM 2
• Atypical antipsychotics (quetiapine, olanzapine): NOT recommended for primary insomnia due to weak evidence and significant metabolic side effects including weight gain and metabolic syndrome 2, 3
• Only suitable for patients with comorbid conditions benefiting from primary drug action 1

Medications Explicitly NOT Recommended

Over-the-counter antihistamines (diphenhydramine, doxylamine) are NOT recommended due to lack of efficacy data, anticholinergic effects causing confusion/urinary retention/fall risk in elderly, daytime sedation, and tolerance development after 3-4 days. 1, 2, 3

• Herbal supplements (valerian) and nutritional substances (melatonin supplements): insufficient evidence of efficacy 1, 2, 3
• Barbiturates, barbiturate-type drugs, and chloral hydrate: outdated with unacceptable safety profiles 1, 3
• L-tryptophan: insufficient benefit 2, 3

Critical Prescribing Principles

All pharmacological treatment must be accompanied by comprehensive patient education covering: 1, 3

• Treatment goals and realistic expectations
• Safety concerns and potential side effects
• Drug interactions and contraindications
• Availability of cognitive-behavioral treatments
• Potential for dosage escalation
• Risk of rebound insomnia upon discontinuation

Follow patients regularly—every few weeks initially—to assess effectiveness, side effects, and ongoing medication need. 1, 3

Use the lowest effective maintenance dosage and taper medication when conditions allow; CBT-I facilitates successful discontinuation. 1, 3

Long-term administration may be nightly, intermittent (e.g., three nights per week), or as-needed to reduce tolerance and dependence. 1, 3

Chronic hypnotic medication may be indicated for long-term use in severe/refractory insomnia or chronic comorbid illness, but requires consistent follow-up, ongoing effectiveness assessment, adverse effect monitoring, and evaluation for new/worsening comorbid disorders. 1, 3

Special Population Considerations

Elderly Patients (≥65 years):

• Zolpidem maximum 5 mg due to increased sensitivity and fall risk 2, 3
• Ramelteon 8 mg or low-dose doxepin 3 mg are safest choices due to minimal fall risk and cognitive impairment 2, 3
• Avoid long-acting benzodiazepines completely due to drug accumulation, prolonged daytime sedation, increased fall/fracture risk, and cognitive impairment 2, 3

Patients with Substance Use History:

• Ramelteon is the only appropriate choice due to zero abuse potential and non-DEA-scheduled status 2, 3
• Avoid traditional benzodiazepines which have higher potential for abuse, tolerance, and severe withdrawal syndrome 2

Patients with Hepatic Impairment:

• Zaleplon dose reduced to 5 mg (clearance reduced 70% in compensated cirrhosis, 87% in decompensated cirrhosis) 2
• Eszopiclone reduced to 1 mg maximum 2
• Ramelteon and low-dose doxepin remain safe options 2

Pregnant Patients:

• Using zolpidem in last trimester may cause breathing difficulties or excess sleepiness in newborn; monitor for sleepiness, trouble breathing, or limpness 4
• Zolpidem passes into breast milk; discuss feeding options with provider 4

Critical Safety Warnings

All BzRAs may cause complex sleep behaviors (sleep-driving, sleep-walking, eating, talking, having sex while not fully awake) that have caused serious injury and death. 5, 4

Stop medication immediately and call provider if patient discovers they performed activities while not fully awake. 5, 4

Do NOT prescribe if patient: 5, 4

• Has ever experienced complex sleep behavior after taking hypnotics
• Drank alcohol that evening or before bed
• Takes other medicines causing sleepiness (without provider approval)
• Cannot get full night's sleep (7-8 hours)

Take medication right before getting in bed, not sooner, and never with or right after a meal. 5, 4

Morning-after ability to drive safely and think clearly may be decreased; warn patients not to drive or perform dangerous activities until fully awake. 5, 4

If insomnia persists beyond 7-10 days of treatment, reassess for underlying sleep disorders (sleep apnea, restless legs syndrome, circadian rhythm disorders). 2, 5, 4

Common Pitfalls to Avoid

• Failing to initiate CBT-I before or alongside pharmacotherapy 1, 2, 3
• Using traditional benzodiazepines (lorazepam, diazepam) as first-line treatment instead of non-benzodiazepine BzRAs 2, 3
• Prescribing trazodone for insomnia (explicitly not recommended by AASM) 2, 3
• Using over-the-counter antihistamines or herbal supplements with limited efficacy data 1, 2, 3
• Continuing pharmacotherapy long-term without periodic reassessment 1, 2, 3
• Failing to consider drug interactions and contraindications 1, 2
• Using doses appropriate for younger adults in elderly patients (e.g., zolpidem requires 5 mg maximum in elderly) 2, 3
• Prescribing sedating agents without considering specific effects on sleep onset versus maintenance 2
• Using mirtazapine PRN instead of scheduled nightly dosing 2