Baseline Insomnia Severity Index Score
Severe insomnia recorded before orexin antagonist therapy begins.
- 0–28: ISI score range (clinician/self-rated scale)
- ≥22: Severe cutoff (defines this baseline)
- 7: Items assessed (sleep and daytime domains)
- DORA: Drug class (dual orexin receptor antagonist)
Seven-item questionnaire
Items rate onset, maintenance, satisfaction, and daytime impact.
Severity threshold
A score of 22 or higher marks severe insomnia.
Why orexin antagonists
They block wake-promoting signaling instead of sedating broadly.
Early Improvement in Sleep Onset and Maintenance
First two weeks bring modest gains in falling and staying asleep.
- ~-15%: Onset latency change (typical by week 2)
- Fewer: Night awakenings (early orexin suppression effect)
- ~17–19h: Lemborexant half-life (supports maintenance benefit)
- Highest: Dropout risk (during weeks 1–2)
Onset and maintenance lead
Falling and staying asleep improve before daytime symptoms.
Adherence matters early
Missed doses blunt gains during this fragile window.
Side-effect monitoring
Next-day somnolence is checked closely at this stage.
Moderate Range Improvement by Treatment Week Four
Total score shifts from severe into the moderate insomnia band.
- 15–21: Target ISI band (moderate insomnia range)
- Week 4: Typical visit (first efficacy checkpoint)
- ↑ steadily: Sleep efficiency (measured by actigraphy)
- Additive: CBT-I combo effect (when paired with therapy)
Moderate range entry
Score typically crosses below 22 by this visit.
Daytime items lag
Interference and distress items improve more slowly.
Titration decisions
Dose or behavioral add-ons considered if response stalls.
Continued Improvement Toward the Subclinical Range
By week eight, scores approach the subthreshold insomnia band.
- 8–14: Target ISI band (subthreshold insomnia range)
- Sustained: Response trajectory (gains hold across weeks)
- Notable: Functional gains (daytime interference eases)
- Low: Tolerance risk (for DORA class at 8 weeks)
Nearing subthreshold
Most items fall below moderate severity by now.
Functioning recovers
Concentration and mood benefit from consolidated sleep.
Maintenance planning
Clinicians plan whether to continue or taper therapy.
Clinically Meaningful Treatment Response Achieved
A drop of seven or more points marks a genuine treatment response.
- ≥7 pts: MCID threshold (minimal clinically important difference)
- ≤7: Remission target (ISI score for full remission)
- ~60–70%: Response rate (reported in DORA trials)
- Ongoing: Relapse watch (periodic ISI re-scoring advised)
Defining response
A seven-point drop is considered clinically meaningful.
Remission goal
Scores at or below seven indicate full remission.
Long-term follow-up
Periodic rescoring guards against symptom relapse.