The use of Modafinil

Position Statement: The use of Modafinil

Excessive Daytime Sleepiness

Excessive daytime sleepiness (EDS) is increasingly recognised as a potentially serious symptom worthy of assessment and possible treatment. Excessively sleepy patients appear in general medical and psychiatry clinics as well as those dedicated to sleep medicine. The commonest cause of EDS across the population is poor sleep hygiene (insufficient sleep opportunity and/or an irregular sleep pattern). However, EDS is also a feature of many ‘medical’ sleep problems. The more common causes include Obstructive Sleep Apnoea (OSA) and Restless Legs Syndrome (RLS).

Additionally, a significant proportion of subjects with EDS have a primary (‘central’) cause for their symptoms. In these individuals, there is presumed or proven neurological dysfunction in the brain’s ‘sleep centres’, most typically the hypothalamus in cases of classical Narcolepsy with Cataplexy. However, there are a number of situations where the diagnosis remains uncertain or there are atypical features. For example, if the strict criteria for diagnosing narcolepsy are not met, the term Idiopathic Hypersomnia is often used although this is almost certainly a heterogeneous diagnosis. These patients are generally sleepy despite good sleep hygiene with 8-10 or more hours of sleep opportunity. They are often able to sleep in the daytime for hours at a time and still feel un-refreshed on waking.

A number of sleepy subjects, therefore, have unclear diagnoses with symptoms that are sufficiently severe to justify empirical treatment strategies. This patient group is not large in number and since the underlying aetiologies are also heterogeneous, it is unlikely that they will ever attract the investment required to develop licensed drug treatments.

Modafinil
Modafinil has been widely used as a wake-promoting agent for over 12 years and has largely replaced less specific psycho-stimulant therapies that are usually amphetamine-like in their action (Dexamphetamine, Methylphenidate etc). As such, it is widely regarded as a safer option from several perspectives. Indeed, in clinical practice, it is generally perceived as a useful drug that will improve alertness whatever the cause of the underlying somnolence with very few adverse consequences. In Europe and other parts of the world Modafinil has been used (and indeed was previously licensed) for ‘softer’ indications such as Shift Work Sleep Disorder. It has also been advocated for ‘recreational’ or ‘occupational/academic’ enhancement. However, in the UK it has been more selectively prescribed (often under specialist direction) for profoundly sleepy patients whose lives have been devastated economically, occupationally and often socially by their profound level of sleepiness.

More recently there have been safety concerns over the use of Modafinil. The European Medicines Agency (EMA) has recommended a restriction in licensing to narcolepsy only. The predominant concerns relate to potential increases in systolic blood pressure, a possible link to severe skin reactions seen in a few young subjects, and non-specific psychiatric side-effects.

This restriction has caused concern for many clinicians dealing with sleep disorders, particularly in view of the lack of effective or safe alternative treatments. Patients who have been managing well on Modafinil for years may now find that they are no longer able to obtain a prescription. Many patients are rendered profoundly sleepy without medication and are unable to work, fulfil their family commitments and relationships my break up. They may be unable to drive or may suffer accidents at work and in the home. Patients may be left with little choice but to either suffer or use less safe alternatives that may be obtained illegally.

Recommendations
The BSS recommends that Modafinil should remain an available treatment in sleep disorders causing EDS provided potential side effects are closely monitored. As with the majority of drugs prescribed in sleep medicine, its use would be ‘off licence’ and most appropriately recommended from secondary care. Examples of situations where Modafinil might be used with caution include EDS in Myotonic Dystrophy, Parkinson’s Disease and Multiple Sclerosis. Idiopathic Hypersomnia also responds well to Modafinil despite a lack of evidence from controlled studies. Subjects with OSA and residual EDS (despite optimal airway treatment with CPAP) may also benefit from supplementary Modafinil. However, particular care is needed when monitoring blood pressure in this group who are predisposed to other cardiovascular risk factors such as Hypertension, Hyperlipidaemia and Type-2 Diabetes Mellitus.

Specifically:

  • Patients with significant EDS should be assessed in a Sleep Clinic.
  • Those with significant EDS without a treatable/successfully treated cause may be considered for a trial of Modafinil.
  • The risks of treatment should be explained fully to ensure that both patient and doctor agree that potential benefits outweigh those risks.
  • Treatment effectiveness should be monitored and Modafinil stopped if little or no benefit is apparent or significant side effects arise.
  • A written Shared Care Agreement should be established between primary care and the sleep clinic to facilitate managing these patients and to support primary care colleagues with prompt advice.

Modafinil is not a cheap treatment and arguments that it is not cost effective may be made. However, data on this are lacking. The recent concerns have focussed solely on side effects which are either relatively easy to monitor or extremely rare and should not, in the opinion of most ‘sleep’ clinicians, severely limit prescribing this useful drug. It must be remembered that profound EDS can ruin a patient’s quality of life, their employment prospects and make them accident prone. There are few therapeutic choices for treating EDS and Modafinil has very often been proven to be effective.

On behalf of the British Sleep Society
PO Box 247
Colne
Huntingdon
Cambridgeshire
PE28 3UZ

Email: bssoffice@btopenworld.com
Web: www.sleeping.org.uk