A patient with refractory insomnia who has failed temazepam 30 mg and multiple other hypnotics, sleeping only about 2 hours continuously, and has a polysomnography scheduled in one month—what is the strongest safe interim therapy?

Strongest Interim Therapy for Refractory Insomnia

For this patient with severe refractory insomnia sleeping only 2 hours nightly after failing temazepam 30 mg and multiple other hypnotics, I recommend adding low-dose quetiapine 25-50 mg at bedtime OR switching to suvorexant 10-20 mg, while immediately initiating Cognitive Behavioral Therapy for Insomnia (CBT-I) and ensuring a sleep study is completed to rule out primary sleep disorders.

Critical First Step: Rule Out Primary Sleep Disorders

Before escalating pharmacotherapy, this patient must be evaluated for occult sleep-disordered breathing, restless legs syndrome, or periodic limb movement disorder, as these conditions masquerade as treatment-resistant insomnia and will not respond to hypnotics alone 1, 2. The scheduled polysomnography in one month is essential—do not delay this study 3.

• Screen immediately for obstructive sleep apnea symptoms: witnessed apneas, loud snoring, morning headaches, excessive daytime sleepiness, hypertension 1
• Ask specifically about restless legs symptoms: uncomfortable leg sensations at rest, urge to move legs, symptoms worse in evening, relief with movement 3
• If high clinical suspicion exists, consider expediting the sleep study rather than adding more sedatives that may worsen undiagnosed sleep apnea 1

Strongest Pharmacologic Options for One-Month Bridge

Option 1: Low-Dose Quetiapine (Off-Guideline but Clinically Effective)

Quetiapine 25-50 mg at bedtime is recommended by NCCN palliative care guidelines specifically for refractory insomnia when first-line agents have failed 3. While the American Academy of Sleep Medicine guidelines from 2016 recommend against quetiapine due to metabolic risks 3, the NCCN guidelines explicitly position it for cases like this where multiple hypnotics have failed 3.

• Start quetiapine 25 mg at bedtime, increase to 50 mg after 3-5 nights if insufficient response 3
• Monitor for: orthostatic hypotension (especially first week), morning sedation, metabolic effects (weight gain, glucose) 3
• Advantage: Often effective when benzodiazepines and Z-drugs have failed; no abuse potential 3
• Disadvantage: Metabolic side effects, extrapyramidal symptoms, not FDA-approved for insomnia 3

Option 2: Suvorexant (Orexin Antagonist—Different Mechanism)

Suvorexant 10-20 mg represents a mechanistically distinct approach via orexin receptor antagonism, appropriate when benzodiazepine receptor agonists have failed 3, 4, 5.

• Start suvorexant 10 mg at bedtime, increase to 20 mg after one week if needed (maximum dose for non-elderly adults) 4, 5
• Evidence: Reduces wake after sleep onset by 16-28 minutes with moderate-quality evidence 3, 4
• Advantage: Different mechanism than failed temazepam; lower risk of complex sleep behaviors than Z-drugs 4, 5
• FDA data: Effective for both sleep onset and maintenance in 3-month trials 5
• Critical warning: Can cause next-morning driving impairment; counsel patient to allow ≥7 hours before driving 5

Option 3: Combination Low-Dose Doxepin + Existing Regimen

Doxepin 3-6 mg at bedtime specifically targets sleep maintenance via selective H₁-histamine antagonism with minimal anticholinergic effects at hypnotic doses 3, 4.

• Start doxepin 3 mg at bedtime, increase to 6 mg after one week if insufficient 3, 4
• Evidence: Reduces wake after sleep onset by 22-23 minutes with moderate-quality evidence 3, 4
• Advantage: No abuse potential, minimal drug interactions, can be combined with other agents 3, 4
• Best for: Patients with predominantly sleep-maintenance insomnia (frequent awakenings) 3, 4

Mandatory Concurrent Intervention: CBT-I

Cognitive Behavioral Therapy for Insomnia (CBT-I) must be initiated immediately, as it provides superior long-term outcomes compared to medications alone and is the only intervention with sustained benefits after discontinuation 3, 4.

• Core components to implement now:

  • Stimulus control: Bed only for sleep/sex; leave bedroom if awake >20 minutes; consistent wake time 3, 4
  • Sleep restriction: Limit time in bed to actual sleep time + 30 minutes (if sleeping 2 hours, allow only 2.5 hours in bed initially) 3, 4
  • Cognitive restructuring: Address catastrophic thinking about sleep consequences 3, 4
  • Sleep hygiene: No caffeine after 2 PM, no alcohol, dark/cool bedroom, no screens 1 hour before bed 3, 4

• Delivery options: Individual therapy, telephone-based programs, web-based modules (e.g., Sleepio, CBT-I Coach app), or self-help books—all formats show effectiveness 3, 4

What NOT to Do

Avoid these common pitfalls in refractory insomnia:

• Do NOT add another benzodiazepine (e.g., lorazepam, clonazepam) after temazepam failure—cross-tolerance makes this futile and increases fall/cognitive impairment risk 3, 4
• Do NOT use trazodone—explicitly not recommended by AASM guidelines due to minimal benefit (10-minute reduction in sleep latency) with no improvement in subjective sleep quality 3, 4
• Do NOT use diphenhydramine or other antihistamines—lack efficacy data, cause anticholinergic effects, and tolerance develops within 3-4 days 3, 4
• Do NOT combine multiple CNS depressants (e.g., adding a Z-drug to a benzodiazepine)—markedly increases respiratory depression, falls, and cognitive impairment risk 3, 4
• Do NOT continue current ineffective regimen unchanged—if temazepam 30 mg provides only 2 hours of sleep, it has clearly failed and should be tapered off 3

Specific Treatment Algorithm for This Patient

1. Week 1-2:

   • Start suvorexant 10 mg OR quetiapine 25 mg at bedtime (choose based on patient preference and comorbidities) 3, 4, 5
   • Begin tapering temazepam by 25% every 1-2 weeks to avoid withdrawal 3
   • Initiate CBT-I with focus on stimulus control and sleep restriction 3, 4
   • Reassess after one week: sleep latency, total sleep time, nocturnal awakenings, daytime functioning 3, 4

2. Week 2-4:

   • If insufficient response: Increase suvorexant to 20 mg OR quetiapine to 50 mg 3, 4, 5
   • Continue temazepam taper (should be off by week 4) 3
   • Optimize CBT-I: Adjust sleep restriction based on sleep diary data 3, 4

3. At polysomnography (1 month):

   • If sleep apnea diagnosed: Initiate CPAP/BiPAP; hypnotics may worsen apnea 3, 1
   • If restless legs/PLMD diagnosed: Add ropinirole or pramipexole with pregabalin 3
   • If no primary sleep disorder: Continue current regimen and plan gradual medication taper as CBT-I effects consolidate 3, 4

Critical Safety Monitoring

• Assess weekly for:

  • Complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating)—discontinue medication immediately if these occur 3, 4, 5
  • Morning sedation or driving impairment—particularly with suvorexant 20 mg 5
  • Falls or cognitive impairment—especially if elderly 3
  • Metabolic changes if using quetiapine (weight, glucose, lipids at 1 month) 3

• Document at each visit:

  • Sleep-onset latency, total sleep time, number of awakenings, daytime functioning 3, 4
  • Adverse effects and medication adherence 3, 4
  • Progress with CBT-I techniques 3, 4

Long-Term Plan

After polysomnography results and 4-8 weeks of combined pharmacotherapy + CBT-I:

• If improved: Begin gradual medication taper using CBT-I to maintain gains; aim for medication-free sleep within 3-6 months 3
• If still refractory: Refer to sleep medicine specialist for comprehensive evaluation of perpetuating factors and consideration of alternative diagnoses 3, 2
• FDA guidance: Pharmacologic treatments are intended for short-term use (≤4 weeks for acute insomnia); evidence does not support routine long-term use beyond this period 3