Options For Wake-Promoting Medication For Narcolepsy

In managing narcolepsy, it’s usually a matter of using a combination of non-drug strategies such as napping and managing commitments together with medications to help people stay awake and, if needed, additional medications to manage other symptoms such as cataplexy or sleep disturbance. The 3 most commonly used wake-promoting medications are modafinil, dexamphetamine and methyphenidate (Ritalin). Also, sodium oxybate (Xyrem) has become available in Australia under the Special Access Scheme.

Medication for narcolepsy. What is used?

Modafinil (Modavigil in Australia, Provigil in US): Modafinil is a wakefulness-promoting drug (eugeroic) with a duration of action of around 6-12 hours. It comes in 100mg tablets, and in narcolepsy is used at doses of up to 400mg daily. Although modafinil is reasonably long acting, it can be taken in divided doses with a second dose around the middle of the day. Exactly how modafinil works is not clear, but it seems to be more selective than the other medications, working predominately on wake-promoting centres in the brain. This means it is less likely to cause side effects of over stimulation or cardiovascular effects than the other medications.

Dexamphetamine:  is an amphetamine-based psychostimulant that has been used as a treatment for narcolepsy for many years. It comes in 5mg tablets and can be used at doses of up to 60mg daily. It has duration of action of 3-6 hours and the effect comes on quickly, usually within 30 minutes, which means it can be taken as 2-3 doses across the day. Dexamphetamine works by activating the sympathetic nervous system, the ‘fight flight response’ so, in addition to helping people feel more awake, can increase alertness and give a sense of being ‘on’. It can also increase heart rate and over time lead to high blood pressure or heart wall thinkening. Dexamphetamine is available on the PBS in Australia. As it’s an old medication it’s very cheap, so even without PBS subsidy it is around $15 for 100 tablets. New formulations of dexamphetamine that are longer acting such as Vyvanse are now available in Australia. However these are not approved for use in narcolepsy and not subsidised on the PBS. The cost is around $130 for 30 x 30mg tablets.

Methylphenidate (Ritalin / Concerta): Methylphenidate, is chemically somewhat different from dexamphetamine, but is also a psychostimulant that is also used to treat attention deficit disorder. As Ritalin acts in a similar way to dexamphetamine, activating the sympathetic nervous system, effects and side effects are similar to dexamphetamine. Ritalin comes in a range of tablet sizes and both long and short acting formulations and can be used in doses up to 60mg daily. Short-acting forms come in 10mg tablets, and long-acting forms (Ritalin LA) comes in 10, 20, 30 and 40mg. Another formulation of methylphenidate called Concerta is also available in Australia. It is a long-acting formulation and comes in doses of 18, 36 and 54mg. Methylphenidate is not subsidised on the PBS in Australia for the treatment of narcolepsy. It costs around $10 for 100 x 10mg Ritalin tablets, $40 for 30 x 30mg Ritalin LA tablets, and $54 for 30 x 36mg Concerta tablets.

Sodium Oxybate (Xyrem): Different to other wake-promoting medications, rather than turning on or activating the ‘wake system’, sodium oxybate reduces sleepiness through having positive effects on sleep, sleep quality and possibly by reducing sleep drive. Sodium oxybate comes in liquid form (500mg/ml in 180ml bottles) and is used at doses of up to 9grams per night in 2 divided doses. It has a duration of action of 2-4 hours, so a dose is taken on getting in to bed, then around 2-4 hours later. Sodium oxybate works by acting on the GABA and GHB receptors. As sodium oxybate is a powerful sedative the most common side effect is over-sedation which can be severe enough to suppress breathing if the dose is too high.

How are medications used in practice?

To give you an idea of which medications are used, the graph below shows the proportion of people with narcolepsy on different wake-promoting medications in my practice. This was an audit of 91 people with narcolepsy I managed in 2013.

The interesting points for me are:

  • 20% of people were on no wake-promoting medications
  • 13% (1 in 8) were on a combination of medications
  • People with cataplexy were more likely to be on modafinil (56% vs 37%). Whereas those without cataplexy were more likely to be on dexamphetamine (25% vs 9%). I think this relates to the PBS criteria in Australia which make it easier to access modafinil for those with a clear history of cataplexy.

Side effects and how to minimise them

Side effects from wake-promoting medications are common, but there are some strategies that can be used to minimise side effects or reduce the risk of them occurring:

  • Don’t rely on medications to do all the work. Make sure non-drug strategies such as napping, managing general health and not over-committing are also part of your treatment plan.
  • Don’t expect too much from the medications and aim to use the minimum dose required to get a reasonable effect
  • Have a break from wake-promoting medications periodically. This seems to be less important with modafinil, but for dexamphetamine and methylphenidate having some time off medication can ‘reset’ tolerance that develops. No hard and fast rules for how often or how long, but if you feel that medications are becoming less effective look ahead at your schedule and see where you could manage a week or so off medication

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