Narcolepsy

What is the DSM-5 criteria for narcolepsy?

Recurring episodes of excessive daytime sleepiness with ONE OR MORE of the following:

- Cataplexy

- CSF hypocretin deficiency (< 110 pg/mL)

- Mean sleep latency ≤ 8 minutes

Occurring at least 3 times/week and lasting at least 3 months

What does CHESS stand for in narcolepsy?

Cataplexy

Hallucinations

Excessive daytime sleepiness

Sleep paralysis

Sleep disruption

What are non-pharmacologic interventions for narcolepsy?

Psychosocial support

Notify people

Schedule naps for 10-20 min every 2 hours

Avoid sedating medications

Health maintenance of comorbid conditions

Driving safety considerations

What pharmacologic classes can treat narcolepsy?

Stimulants

CNS Depressant

Histamine-3 Receptor Antagonist

Dopamine and NE Reuptake Inhibitor (DNRI)

Antidepressants

Which narcolepsy drugs are stimulants?

FDA approved:

- Modafinil (Provigil)

- Armodafinil (Nuvigil)

NOT FDA approved:

- Methylphenidate (Ritalin)

- Dextroamphetamine (Dexedrine)

When should modafinil and armodafinil be dose adjusted?

Reduce dose in hepatic impairment

What are ADEs of modafinil and armodafinil?

RASH (1-5 weeks)

HTN, GI upset, insomnia, psychiatric sx

What class of controlled substance is modafinil and armodafinil?

C-IV substance = abuse potential

Describe the metabolism of modafinil and armodafinil

CYP2C19 inhibitors

What can modafinil and armodafinil decrease the effectiveness of?

Decreased oral contraceptive effectiveness

Describe the aspects of metabolism that are specific to modafinil

CYP3A4 substrate & AUTO-INDUCER

Describe plasma concentrations with armodafinil

Higher plasma concentrations later in the day = insomnia

Which narcolepsy drug is a dopamine and NE reuptake inhibitor (DNRI)?

Solriamfetol (Sunosi)

When should solriamfetol be dose adjusted?

Reduce dose in renal impairment

What are ADEs of solriamfetol?

INCREASE IN BP & HR

Psychiatric sx, decreased appetite, N/V, insomnia, anxiety

When should solfiamfetol be taken?

Once daily upon awakening, no sooner than 9 hours before bed

When is solriamfetol contraindicated and why?

Contraindicated with MAOIs due to solriamfetol's serotonergic properties

When should solriamfetol be used with caution?

Caution in psychosis

Which narcolepsy drug is a histamine-3 receptor antagonist?

Pitolisant (Wakix)

When should pitolisant be dose adjusted?

Reduce dose in hepatic & renal impairment

What are ADEs of pitolisant?

QTc PROLONGATION

Insomnia, N/V, anxiety

How often should pitolisant be taken?

Once daily in the AM

What can pitolisant reduce the efficacy of?

Can reduce efficacy of hormonal contraceptives

When is pitolisant contraindicated?

Contraindicated in severe hepatic impairment and ESRD

Describe the metabolism of pitolisant

Metabolized by CYP2D6

Reduce dose with poor metabolizers

Which narcolepsy drug is a CNS depressant?

Sodium oxybate (Xyrem or Lumryz)

What are ADEs of sodium oxybate?

CONFUSION, DISORIENTATION

N/V, dizziness

What schedule controlled substance is sodium oxybate?

C-III with REMS program

How often is Xyrem dosed?

BID

What should be done and avoided after taking sodium oxybate?

DO = lie down in bed after dosing

AVOID driving for at least 6 hours

What risk is associated with sodium oxybate use?

Risk of parasomnias

How long can it take for sodium oxybate to take full effect?

Up to 3 months for full effect

Which antidepressants are used for cataplexy in narcolepsy?

SSRIs, Venlafaxine, TCAs, selegiline