Treatment of Cataplexy in Adults
Sodium oxybate is the first-line treatment for cataplexy in adults with narcolepsy, as it is FDA-approved and demonstrates clinically significant improvements in both cataplexy frequency and excessive daytime sleepiness. 1, 2, 3
First-Line Pharmacological Treatment
Sodium Oxybate (Xyrem/Xywav)
The American Academy of Sleep Medicine strongly recommends sodium oxybate as the primary treatment for cataplexy in adults with narcolepsy, based on moderate-quality evidence from 6 RCTs and 6 observational studies showing clinically significant improvements in cataplexy attacks, excessive daytime sleepiness, and disease severity. 4
Sodium oxybate is administered as a liquid in two equally divided doses at night: the first dose at bedtime and the second dose 2.5-4 hours later. 1, 3
The medication is FDA-approved for treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy. 3
Clinical trial data demonstrate that patients randomized to placebo after stable sodium oxybate treatment experienced significant worsening in weekly cataplexy attacks compared to those continuing treatment, establishing robust efficacy. 3
Pitolisant
- Pitolisant (a histamine-3-receptor inverse agonist) is also effective for cataplexy management and has the advantage of not being a controlled substance. 1, 2
Critical Safety Considerations for Sodium Oxybate
Black Box Warnings and Controlled Substance Status
Sodium oxybate carries an FDA black box warning as it is a central nervous system depressant that may cause respiratory depression; use with extreme caution in patients with respiratory conditions. 1, 5
This medication is an FDA Schedule III controlled substance (sodium salt of gamma hydroxybutyrate/GHB) and is only available through the Risk Evaluation Mitigation Strategy (REMS) program using certified pharmacies. 4, 5
Common Adverse Events
Frequently reported adverse events include nausea, dizziness, nocturnal enuresis, headache, chest discomfort, sleep disturbances, and confusion. 4
In real-world clinical practice, approximately 50% of patients experience at least one side effect, and 26.6% discontinue treatment due to limiting adverse effects. 6
Nausea, mood swings, and enuresis are the most commonly reported side effects in routine clinical practice. 6
Special Population Considerations
For elderly patients, careful monitoring is required due to potential adverse effects, particularly psychosis, which is associated with increasing age and typically occurs early after drug initiation. 1, 5, 6
Dosing should be initiated at lower levels and titrated more gradually in elderly patients. 1
The balance of risks and harms is likely different for pregnant and breastfeeding women. 4
Second-Line Pharmacological Options
Antidepressants
Antidepressants are effective for cataplexy control, particularly those affecting norepinephrine and serotonin systems (TCAs and SSRIs). 1, 7
TCAs were found beneficial for cataplexy treatment over 40 years ago, and SSRIs have been used more recently. 7
Stimulants (for Excessive Daytime Sleepiness, Not Cataplexy)
Note that solriamfetol, armodafinil, modafinil, dextroamphetamine, and methylphenidate are recommended for excessive daytime sleepiness but do NOT directly treat cataplexy. 4
Approximately 59% of patients in clinical trials continued taking a stable dose of CNS stimulant alongside sodium oxybate for management of daytime sleepiness. 3
Dosing and Titration Strategy
Initial Dosing
Patients not previously taking sodium oxybate should be initiated at 4.5 g/night and titrated at a rate of 1 or 1.5 g/night/week to a tolerable and effective dose. 3
The recommended adult dosage range is 6-9 g/night, with at least 6 g needed to adequately reduce both cataplexy and daytime drowsiness. 8
Dose Adjustments
In clinical trials, 69% of patients switching from Xyrem to the lower-sodium formulation (Xywav) had no dosage change; 27% required an increase, and 3% required a decrease. 3
Most dosage changes were within one titration step (≤1.5 g). 3
The required maintenance dose cannot be predicted based on gender, body mass index, or clinical factors. 6
Non-Pharmacological Management
Behavioral Modifications
Maintaining good sleep hygiene and regular sleep-wake schedules can help control cataplexy. 1
Occupational considerations include avoiding shift work and on-call schedules. 1
Monitoring and Follow-Up
Regular Assessment Requirements
Regular assessment of cataplexy frequency and severity is necessary to evaluate treatment efficacy. 1
Monitor for medication side effects, particularly respiratory depression, enuresis, nausea, and headache with sodium oxybate. 1, 5
Watch for cataplexy exacerbation if any medication affecting adrenergic systems is initiated, as the loss of hypocretin-producing neurons suggests adrenergic systems are downstream mediators of cataplexy pathology. 1, 2
Medication Reduction Potential
- In real-world practice, 60% of patients on sodium oxybate were able to reduce or discontinue other medications for narcolepsy. 6
Common Pitfalls to Avoid
Diagnostic Errors
- Failure to recognize cataplexy as distinct from seizures or other neurological conditions can lead to misdiagnosis and inappropriate treatment. 1
Treatment Inadequacy
- Inadequate treatment of both excessive daytime sleepiness and cataplexy components can worsen overall symptom burden; both symptoms require attention. 1
Drug Interactions
Co-administration with divalproex sodium increases GHB exposure by approximately 25% and causes greater impairment on attention and working memory tests than either drug alone. 3
Altered consciousness and respiratory depression can occur after a single intake of a dose two or three times higher than recommended. 8
Misuse Potential
- The odorless and colorless nature of the oral solution facilitates misuse, including potential for chemical or drug-induced submission ("date rape" drug). 8
Referral Considerations
- Primary care physicians should refer patients to a sleep specialist when narcolepsy with cataplexy is suspected for proper diagnosis and treatment initiation. 1