narcolepsy/RLS

Typical age peaks for narcolepsy onset?

15 years and ~35 years.

What is the DSM-5 definition of narcolepsy?

Recurrent episodes of irresistible need to sleep or napping ≥3x/week for ≥3 months plus at least one of:

1. Cataplexy (a few times per month).

2. Hypocretin deficiency (low CSF).

3. REM latency ≤15 min on PSG or MSLT with ≥2 sleep-onset REM periods.

How is narcolepsy severity rated?

• Mild: Cataplexy <1/week.

• Moderate: Cataplexy daily-every few days, disturbed sleep.

• Severe: Multiple daily cataplexy attacks, constant sleepiness, resistant to meds.

What are the four classic symptoms (tetrad) of narcolepsy?

• Excessive daytime sleepiness (EDS).

• Cataplexy.

• Hypnagogic/hypnopompic hallucinations.

• Sleep paralysis.

Which symptom is present in nearly all narcolepsy patients?

Excessive daytime sleepiness (100%).

What autoimmune mechanism is thought to cause narcolepsy?

Destruction of hypocretin (orexin)-producing neurons.

What family history risk is associated with narcolepsy?

10–40× higher risk if first-degree relative affected.

What lifestyle strategies are recommended for narcolepsy?

• Regular sleep schedule.

• Avoid alcohol/CNS depressants.

• Scheduled naps (10–30 min every 2h).

• Use modest caffeine.

• Avoid shift work.

• Educate family/friends.

First-line treatment for EDS in narcolepsy?

Modafinil.

What are second-line options for EDS if modafinil not sufficient?

Dextroamphetamine, (dexedrine), Methylphenidate (Ritalin)

Newer alternatives for EDS in narcolepsy?

Solriamfetol, Pitolisant.

Efficacy of modafinil in narcolepsy?

A: Improves vigilance, ↓ daytime sleep episodes, little effect on nighttime sleep.

PK of modafinil?

Onset <1h, duration 6–8h.

Common adverse effects of modafinil?

↑ BP, headache, nausea, anxiety, insomnia, GI upset, dizziness.

Serious adverse effects of modafinil?

Rash (SJS), psychiatric symptoms (mania, psychosis, suicidality), cardiovascular events.

Efficacy of stimulants in narcolepsy?

Improve alertness, mood, daytime performance.

Adverse effects of stimulants?

↑ BP, HR, sweating, irritability, weight loss, insomnia, tolerance, risk of diversion.

Contraindications to stimulants?

Narrow angle glaucoma, hyperthyroidism, moderate-severe HTN, pheochromocytoma, symptomatic CVD, history of mania/psychosis.

Efficacy of solriamfetol?

↑ wakefulness duration slightly more than modafinil vs. placebo.

Adverse effects of solriamfetol?

↑ BP, tachycardia, headache, anxiety, insomnia, decreased appetite.

Contraindication for solriamfetol?

Avoid in unstable CVD, arrhythmias.

Efficacy of pitolisant?

May work as well as modafinil for EDS; modest cataplexy benefit.

MOA of pitolisant?

Histamine-3 receptor inverse agonist → ↑ histamine release in brain

Adverse effects of pitolisant?

Nausea, anxiety, insomnia, QT prolongation.

Q: Important drug interactions with pitolisant?

CYP2D6 inhibitors, CYP3A4 inducers, ↓ efficacy of hormonal contraceptives.

What are first-line treatments for cataplexy?

Sodium oxybate, pitolisant.

What antidepressants are commonly used off-label for cataplexy?

Venlafaxine, Clomipramine (TCAs > SSRIs).

Why should antidepressants for cataplexy be tapered gradually?

Abrupt discontinuation may cause rebound cataplexy or status cataplecticus.

MOA of sodium oxybate?

CNS depressant, GABA-B agonist, improves nocturnal sleep quality.

Efficacy of sodium oxybate in narcolepsy?

↓ cataplexy frequency/severity, ↑ daytime alertness.

Q: Major adverse effects of sodium oxybate?

Nausea, dizziness, sleepwalking, enuresis, disorientation, misuse potential, respiratory depression (boxed warning).

When should patients be followed up after treatment initiation?

4–6 weeks initially, then every 6–12 months.

Difference between primary and secondary RLS?

• Primary: idiopathic, often familial (50% have + family history).

• Secondary: due to conditions like iron deficiency, CKD, endocrine disorders, pregnancy, neuropathy.

Name key risk factors for RLS.

Older age, female sex, iron deficiency (<50 mcg/L), pregnancy, diabetes, hypothyroidism, MS, Parkinson’s, RA, CKD, vitamin deficiencies (B12, folate), electrolyte imbalances, venous insufficiency.

What is the hallmark feature of RLS?

Urge to move legs with uncomfortable sensations, worse at rest, relieved by movement, and more bothersome in evening/night.

What frequency and duration of symptoms od RLS meets DSM-5 criteria?

≥3 times per week for ≥3 months with functional impairment.

What mnemonic summarizes DSM-5 criteria for RLS?

URGE = Urge to move, Rest worsens, Getting up relieves, Evening symptoms.

What are periodic limb movements of sleep (PLMS)?

Forceful, repetitive leg jerks during sleep (occur in ~90% of RLS patients).

What labs should be ordered for suspected RLS?

BC, electrolytes, creatinine, thyroid, fasting glucose, vitamin B6/B12/folate, iron studies (serum iron, ferritin, iron saturation).

Name medications that can cause or worsen RLS.

Antidepressants (mirtazapine, TCAs, lithium, some SSRIs), antipsychotics, dopamine-blocking antiemetics (metoclopramide), antiepileptics (topiramate), sedating antihistamines, calcium channel blockers, alcohol, nicotine, caffeine, withdrawal from sedatives/opioids.

What are the treatment goals in RLS?

Improve motor restlessness & discomfort, improve sleep, reduce PLMS, improve daytime function, minimize rebound/augmentation from drug therapy.

Non-drug strategies for RLS?

Reduce alcohol/caffeine/nicotine, hot baths, stretching, exercise, massage, mental alertness activities, treat iron deficiency, stop offending meds, improve sleep hygiene.

What is first-line therapy if ferritin <75 mcg/L?

Oral iron supplementation.

First-line pharmacologic class for chronic RLS (≥3x/week)?

GABA analogues (gabapentin, pregabalin).

Which agents are 3rd line due to augmentation risk?

Dopamine agonists (pramipexole, ropinirole, rotigotine), levodopa/carbidopa.

What is recommended for intermittent RLS (<3x/week)?

Levodopa/carbidopa (PRN), low-dose opioids, or benzodiazepines.

Why are gabapentin/pregabalin often preferred for chronic RLS?

Good for insomnia, GAD, neuropathy, minimal augmentation risk.

Adverse effects of gabapentin/pregabalin?

Somnolence, dizziness, edema, weight gain (pregabalin).

Common dopamine agonists for RLS?

Pramipexole, ropinirole, rotigotine patch.

What is augmentation in RLS therapy?

Paradoxical worsening of symptoms (earlier onset, more severe, spread to trunk/arms).

What is rebound in RLS therapy?

Recurrence of symptoms late at night/early morning when drug effect wears off.

Adverse effects of dopamine agonists?

Orthostatic hypotension, hallucinations, somnolence, sudden sleep attacks, compulsive behaviors (gambling, hypersexuality).

Why is levodopa/carbidopa restricted to intermittent RLS use?

High risk of augmentation and rebound if used daily.

Adverse effects of levodopa/carbidopa?

Nausea, dizziness, orthostatic hypotension, dry mouth.

Q: What role do opioids play in RLS?

Low-potency opioids (e.g., codeine) may help refractory RLS, but risk dependence & sedation.

What role do benzodiazepines play in RLS?

A: Improve sleep quality but don’t treat core RLS symptoms; risk of sedation and dependence.

How is RLS managed in pregnancy?

Non-drug strategies and iron supplementation; avoid pharmacotherapy (none proven safe).

How is RLS managed in breastfeeding?

Non-drug strategies preferred; dopamine agonists suppress lactation; gabapentin may be considered if necessary.

what should be monitored with dopamine agonists?

Compulsive behaviors, augmentation.

What should be monitored with gabapentin/pregabalin?

Dizziness, falls.