What are the best treatments for insomnia in patients with End-Stage Renal Disease (ESRD) undergoing hemodialysis?

Best Treatments for Insomnia in Hemodialysis Patients

For hemodialysis patients with mild to moderate chronic insomnia, neither cognitive behavioral therapy for insomnia (CBT-I) nor trazodone demonstrates superiority over placebo, and trazodone carries significantly increased cardiovascular risk—therefore, prioritize non-pharmacological interventions including exercise therapy, sleep hygiene optimization, and dialysis adequacy before considering any pharmacological approach. 1

Evidence-Based Treatment Algorithm

Step 1: Optimize Dialysis and Correct Reversible Causes

• Ensure adequate dialysis delivery with minimum three times weekly sessions and achieve target dry weight, as inadequate dialysis and volume overload directly contribute to insomnia 2
• Correct anemia to recommended ranges, which impacts overall well-being and sleep quality 2
• Review all medications for side effects that may worsen sleep disturbance 2
• Consider nocturnal hemodialysis if available, as it provides better clearance of uremic toxins and may reduce daytime sleepiness, though sleep fragmentation from periodic limb movements often persists 3

Step 2: First-Line Non-Pharmacological Interventions

• Implement structured exercise therapy targeting moderate-intensity physical activity for at least 150 minutes per week, as moderate-quality evidence demonstrates aerobic exercise decreases depressive symptom burden and improves overall symptom management in hemodialysis patients 2
• Initiate cognitive behavioral therapy for insomnia (CBT-I) as it has proven efficacy in reducing depression (which commonly co-occurs with insomnia) in hemodialysis patients, though the 2024 SLEEP-HD trial showed no superiority over placebo specifically for insomnia 2, 1
• Apply music therapy during dialysis sessions with calming and uplifting lyrics, as this reduces stress, anxiety, and pain perception without adverse effects 4

Step 3: Consider Complementary Approaches

• Auricular acupressure therapy (AAT) applied to specific auricular acupoints showed significant improvement in Pittsburgh Sleep Quality Index scores, shorter sleep latency, less sleep disturbance, and reduced dependency on sleep medications (weekly estazolam consumption decreased from 6.98±4.44 to 4.23±2.66 pills, p<0.01) in a pilot study, though effects were not sustained one month after treatment cessation 5
• Sleep trackers and remote monitoring may inform on insomnia patterns and help tailor interventions 6

Pharmacological Approaches: Use With Extreme Caution

Critical Evidence Against Standard Treatments

The landmark 2024 SLEEP-HD randomized controlled trial (n=126) demonstrated that neither CBT-I nor trazodone was more effective than placebo for chronic insomnia in hemodialysis patients. At 7 weeks, ISI score changes were: CBT-I -3.7, trazodone -4.2, placebo -3.1 (no significant differences). Critically, trazodone was associated with significantly higher serious adverse events, particularly cardiovascular events (annualized cardiovascular SAE incidence: trazodone 0.64 vs placebo 0.21 vs CBT-I 0.05) 1

If Pharmacotherapy Is Absolutely Required

• SSRIs have not shown consistent benefit over placebo in hemodialysis patients and carry documented increased adverse effects, particularly gastrointestinal symptoms (nausea occurs 2.67 times more frequently than placebo) 2
• No randomized controlled trials address pharmacological management of anxiety (which commonly co-occurs with insomnia) in kidney failure populations 2, 4
• Zolpidem pharmacokinetics are not significantly altered in end-stage renal disease patients undergoing hemodialysis, with no accumulation after 14-21 days and no need for dosage adjustment 7
• Consider short-acting benzodiazepines or non-benzodiazepine hypnotics (zaleplon, zolpidem) for short-term use only if daytime impairment is severe, using the lowest effective dose for the shortest period possible 6

Medications to Avoid

• Avoid long-acting benzodiazepines (diazepam, clonazepam, lorazepam) due to half-lives longer than 24 hours, active metabolites, and accumulation risk 6
• Avoid antihistamines due to daytime sedation and delirium risk, especially in older patients 6
• Avoid antipsychotics as first-line due to metabolic side-effects and lack of evidence 6
• Do not prescribe trazodone given the increased cardiovascular risk demonstrated in the SLEEP-HD trial 1

Implementation and Monitoring

Assessment Tools

• Use validated screening tools including the Pittsburgh Sleep Quality Index (PSQI), Edmonton Symptom Assessment System-Renal (ESAS-r:R), or Dialysis Symptom Index to quantify insomnia severity 6, 2
• Establish symptom assessment programs with core processes including symptom elicitation, evaluation, management, and clinician follow-up 6

Common Pitfalls to Avoid

• Do not prescribe SSRIs or trazodone as first-line treatment without first optimizing dialysis adequacy, correcting anemia, and attempting non-pharmacological interventions 2
• Avoid polypharmacy burden in this already medically complex population by prioritizing interventions without drug interactions 2
• Do not ignore the placebo response, which was substantial (ISI score reduction of -3.1 to -4.3) in the SLEEP-HD trial, suggesting that attention to sleep concerns and supportive care may be therapeutic 1
• Recognize that uremia itself contributes to daytime sleepiness, with blood urea nitrogen levels correlating with sleep latency (R=0.58, p=0.008), emphasizing the importance of dialysis adequacy 3

Special Considerations

• QT prolongation and altered pharmacokinetics must be considered when prescribing any psychotropic medication in kidney failure 6
• Periodic limb movements are highly prevalent in hemodialysis patients (PLM index 57±47/hr in somnolent patients vs 6±10/hr in alert patients) and contribute to sleep fragmentation, though they are difficult to treat 3
• Acknowledge the power of acknowledgment—even when definitive treatment cannot be offered, validating the patient's sleep concerns and offering coping strategies has therapeutic value 6