Narcolepsy

Medications Used in the Treatment of Narcolepsy

Alerting Agents

Anticataplectic Agents

Alerting Agents (wake-promoting therapeutics and stimulants)

Occasionally, patients prefer to avoid medications and to take extra naps during the day instead. This approach may not provide enough daytime alertness to people suffering from excessive sleepiness associated with narcolepsy function adequately. In these cases, medications classified as alerting agents provide substantial improvements in their daytime alertness. However, for most patients with narcolepsy, alerting agents will not yield a normal degree of daytime alertness. Optimal improvement usually requires scheduled naps.

Modafinil (Provigil, Cephalon) 
Modafinil is a novel wake- promoting medication. It is comparable to traditional stimulants in promoting alertness, but without a number of negative side effects commonly associated with stimulant therapy. The effect may last longer. It is now considered first-line therapy for all newly diagnosed narcolepsy patients or for patients currently demonstrating inadequate response to, or bothersome side effects from, traditional stimulant therapy. 

Modafinil is well tolerated, effective, and extensively studied in narcolepsy. It is often the first-line treatment for narcolepsy.

See Modafinil datasheet for information on dosage and side reactions

If treatment with modafinil alone is not sufficient, traditional stimulants are given with it. 

Traditional stimulants

Commonly used traditional stimulants for narcolepsy include methylphenidate and dextroamphetamine. Other amphetamines, amphetamine-analog agents, and sustained-release preparations are available. 

Many people experience negative effects with these stimulants. It also may exacerbate sleepiness ( rebound hypersomnia) as the dose wears off. The patient may develop tolerance (tachyphylaxis) to the alerting effect with repeated dosing. 

Amphetamines

Common Side effects are: headache, gastrointestinal disturbance, anxiety, irritability, increased pulse, increased blood pressure

Amphetamines are frequently used for narcolepsy and are generally very effective.

See drug information for amphetamines for information about dosage, side effects and warnings.

Methylphenidate

Side effects: headache, gastrointestinal disturbance, anxiety, irritability, increased pulse, increased blood pressure - The side effects are often characterized as not as prominent as in amphetamines.

Commonly used agent for narcolepsy, effective. 

See drug information for methyphenidate for information about dosage, side effects and warnings.

Pemoline (Cylert. Abbott) 

Pemoline in normal doses is less effective in improving daytime sleepiness than methylphenidate, dextroamphetamine, or methamphetamine. This medication also has the potential for hepatotoxicity. Because of these reasons, it is used only when modafinil or traditional stimulants cannot be used. If you use this, regular liver function evaluation is recommended.

Side effects: hepatotoxicity, amphetamine-Iike side effects are generally less pronounced.

This medication was previously used frequently in narcolepsy. But potential for hepatic failure renders pemoline a second- or third-line agent.

See drug information for pemoline for information about dosage, side effects and important safety warnings.

Mazindol

Dosage

Common initial dose - 1-2 mg once or twice daily
Usual maximal dose (carefully monitored higher doses may sometimes be required) - 8 mg in divided doses

Mazindol is generally considered less effective as a stimulant.

See drug information for Mazindol for information about dosage, side effects and important safety warnings.

Medications for Cataplexy (Anticataplectic Agents)

Medications useful in the treatment of cataplexy usually also improve hypnagogic/hypnopompic hallucinations and sleep paralysis. In general, tricyclic antidepressants (TCAs) are effective in ameliorating or eliminating symptoms of cataplexy. Dosage required is much less than that for depression. Disadvantage is the side effects.

Selective serotonin reuptake inhibitors (SSRIs) have also proven useful in treating cataplexy. Doses comparable to that required for depression are required. Also, SSRIs are not as effective as TCAs in some patients. SSRIs, however, may be better tolerated by some than TCAs.

Sodium oxybate (also known as gamma-hydroxybutyrate or GHB) had been used in Europe. It is now undergoing clinical trials in the US. It appears to be an effective   anticataplectic agent, even in individuals with inadequate responses to other agents. GHB is highly effective in reducing nocturnal sleep disruptions and consolidating nocturnal sleep. It also exhibits an alerting effect during the day. 

See Gamma-Hydroxybutyrate (GHB) for more information 

Antidepressants with central nervous system noradrenergic activity have been reported in individual cases to provide effective treatment for cataplexy. Venlafaxine extended-release (Effexor ER) has been found to be particularly effective for cataplexy by a number of clinicians.

Tricyclic antidepressants

Dosage

Common initial dose - 25 mg once or twice daily 
Usual maximal dose  - 150-300 mg divided (doses this high are rarely required)

Side effects: orthostatic hypotension, sedation, anticholinergic effects

TCAs are often more effective, but less tolerable than SSRls

See drug information for TCA for information about dosage, side effects and important safety warnings.

SSRI antidepressants

Dosage

Common initial dose - 20 mg (Prozac and Paxil), 50 mg (Zoloft), daily 
Usual maximal dose 
fluoxetine (Prozac) - 80 mg
paroxetine (Paxil)- 60 mg
sertraline (Zoloft)- 200 mg

Side effects: nausea, insomnia, anxiety, decreased appetite

SSRIs may be less effective than TCAs. But thay are often better tolerated than TCAs.

More Info about side effects, interactions and safety concerns of Prozac, see: drug information for fluoxetine

More Info about side effects, interactions and safety concerns of Paxil, see: drug information for paroxetine

More Info about side effects, interactions and safety concerns of Zoloft, see: drug information for sertraline

Sodium oxybate (Xyrem, Orphan Medical)

Dosage

Common initial dose - 1.5g at HS and 3-4 h later 
Usual maximal dose (carefully monitored higher doses may sometimes be required) - 4.5g at HS and 3-4 h later

Side effects: sedation, nausea, lightheadedness, dizziness

Remarks: usually well tolerated with time; improves nocturnal sleep disruption and can improve daytime sleepiness, FDA approval pending

Venlafaxine (Effexor XR, Wyeth Ayerst)

Dosage

Common initial dose - 37.5 mg once daily
Usual maximal dose  - unknown, but maximum recommended dose for depression is 225 mg

Side effects: nausea, dizziness, sedation

Venlafaxine is not well studied in cataplexy, but clinical reports are promising. It is generally better tolerated than TCAs.

For more Info about side effects, interactions and safety concerns of Venlafaxine, see: drug information for venlafaxine

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