A 21‑year‑old patient taking Vyvanse (lisdexamfetamine) 30 mg reports inability to fall asleep despite using a sleeping aid; how should his stimulant‑induced insomnia be managed?

Management of Stimulant‑Induced Insomnia in a 21‑Year‑Old on Vyvanse 30 mg

Initiate Cognitive Behavioral Therapy for Insomnia (CBT‑I) immediately as first‑line treatment, and if pharmacotherapy is required after 2–4 weeks of CBT‑I, add low‑dose doxepin 3–6 mg at bedtime as the preferred hypnotic for this patient.

Understanding Stimulant‑Induced Sleep Disruption

• Lisdexamfetamine (Vyvanse) has a duration of action extending 13–14 hours post‑dosing, meaning a 30 mg morning dose can interfere with sleep initiation and maintenance well into the evening 1, 2.
• In clinical trials, 19.3% of adults taking lisdexamfetamine reported insomnia as a treatment‑emergent adverse event, though most cases were mild to moderate in severity 2.
• Importantly, the overall Pittsburgh Sleep Quality Index (PSQI) global score did not worsen significantly with lisdexamfetamine compared to placebo (LS mean change –0.8 vs –0.5, P = 0.33), and daytime functioning actually improved significantly (P = 0.0001) 2.

First‑Line Behavioral Intervention (Mandatory Before or Alongside Medication)

• The American Academy of Sleep Medicine and the American College of Physicians issue a strong recommendation that all adults with chronic insomnia receive CBT‑I as the initial treatment before any pharmacotherapy 3, 4.
• CBT‑I provides superior long‑term efficacy compared with hypnotic medications, with sustained benefits for up to 2 years after treatment discontinuation, whereas medication effects cease when stopped 3, 4.

Core CBT‑I Components to Implement Immediately

• Stimulus control therapy: Use the bed only for sleep; if unable to fall asleep within ~20 minutes, leave the bed and engage in a quiet, non‑stimulating activity in dim light until drowsy, then return to bed 3, 4.
• Sleep restriction therapy: Track total sleep time via a sleep log for 1–2 weeks, then limit time in bed to match actual sleep time plus 30 minutes (minimum 5 hours), adjusting weekly based on sleep efficiency (total sleep time ÷ time in bed × 100%) 3, 4.
• Cognitive restructuring: Address maladaptive beliefs such as "I can't sleep without medication" or catastrophic thinking about the consequences of poor sleep 3, 4.
• Relaxation techniques: Practice progressive muscle relaxation, deep breathing exercises, or guided imagery before bed to lower physiological arousal 3, 4.
• Sleep hygiene optimization: Maintain a consistent wake time every day (including weekends), eliminate all caffeine after noon, avoid screens for ≥1 hour before bedtime, keep the bedroom dark, cool, and quiet, and avoid clock‑watching 3, 4.

Pharmacologic Management (Only After CBT‑I Initiation)

Preferred First‑Line Hypnotic: Low‑Dose Doxepin

• Low‑dose doxepin 3 mg at bedtime is the preferred first‑line pharmacologic option for this patient because it reduces wake after sleep onset by 22–23 minutes, has minimal anticholinergic effects at hypnotic doses, carries no abuse potential, and does not worsen stimulant‑related side effects 3.
• If 3 mg is insufficient after 1–2 weeks, increase to 6 mg while maintaining the favorable safety profile 3.
• Doxepin at hypnotic doses (3–6 mg) exhibits minimal anticholinergic activity, making it especially suitable for young adults who may need long‑term therapy 3.

Alternative First‑Line Options (If Doxepin Fails or Is Contraindicated)

• Ramelteon 8 mg at bedtime is appropriate for patients preferring a non‑controlled substance or those with a history of substance use; it improves sleep‑onset latency through melatonin‑receptor agonism with no abuse potential and no withdrawal symptoms 3, 5.
• Eszopiclone 2 mg at bedtime (starting dose for adults <65 years) improves both sleep onset and maintenance, increasing total sleep time by 28–57 minutes with moderate‑to‑large improvements in subjective sleep quality 3.
• Zolpidem 10 mg at bedtime shortens sleep‑onset latency by ~25 minutes and adds ~29 minutes to total sleep time; take within 30 minutes of bedtime with ≥7 hours remaining before planned awakening 3.

Medications Explicitly NOT Recommended

• Trazodone should be avoided because it yields only a ~10‑minute reduction in sleep latency with no improvement in subjective sleep quality, and adverse events occur in ~75% of users 3, 6.
• Over‑the‑counter antihistamines (diphenhydramine, doxylamine) are contraindicated due to lack of efficacy data, strong anticholinergic effects (confusion, daytime sedation), and rapid tolerance development within 3–4 days 3.
• Benzodiazepines (lorazepam, temazepam, clonazepam) should be avoided because of unacceptable risks of dependence, cognitive impairment, falls, and associations with dementia and fractures 3.
• Antipsychotics (quetiapine, olanzapine) must not be used for insomnia; evidence of benefit is weak and they carry significant risks including weight gain, metabolic syndrome, and extrapyramidal symptoms 3.
• Melatonin supplements are not recommended because they produce only a ~9‑minute reduction in sleep latency with insufficient supporting evidence 3.

Implementation Algorithm

1. Week 0: Initiate full CBT‑I program immediately (stimulus control, sleep restriction, cognitive restructuring, relaxation training, sleep hygiene) 3, 4.
2. Week 2–4: Reassess sleep parameters; if CBT‑I alone is insufficient, add low‑dose doxepin 3 mg at bedtime while continuing CBT‑I 3, 4.
3. Week 4–6: If doxepin 3 mg is well‑tolerated but insufficient, increase to 6 mg; if ineffective or not tolerated, switch to ramelteon 8 mg or eszopiclone 2 mg 3.
4. Week 8–12: Reassess efficacy and adverse effects; if sleep consolidates, attempt gradual medication taper while maintaining CBT‑I techniques 3.

Monitoring and Safety

• Reassess sleep‑onset latency, total sleep time, nocturnal awakenings, and daytime functioning after 1–2 weeks of pharmacotherapy 3.
• Screen for complex sleep behaviors (sleep‑driving, sleep‑walking, sleep‑eating) at every visit; discontinue the hypnotic immediately if such behaviors occur 3.
• FDA labeling limits hypnotic use to ≤4 weeks for acute insomnia; continuation beyond this period requires documented rationale and periodic reassessment 3.
• Use the lowest effective dose for the shortest necessary duration, integrating CBT‑I to enable eventual tapering 3.

Common Pitfalls to Avoid

• Do not prescribe a hypnotic without concurrent CBT‑I; this violates strong guideline recommendations and results in less durable benefit 3, 4.
• Do not use the patient's existing "sleeping aid" (likely an OTC antihistamine or inappropriate agent) long‑term; transition to evidence‑based therapy immediately 3.
• Do not combine multiple sedating agents (e.g., adding a benzodiazepine to doxepin), which markedly increases the risk of respiratory depression, cognitive impairment, and falls 3.
• Do not continue pharmacotherapy beyond 4 weeks without periodic reassessment (every 2–4 weeks) to evaluate efficacy, side effects, and ongoing need 3.
• Do not adjust the Vyvanse dose or timing without first implementing CBT‑I and appropriate hypnotic therapy; the stimulant is therapeutically necessary for ADHD management 1, 2.