Drugs that increase alertness (psychostimulants) for excessive daytime sleepiness (hypersomnia) in myotonic dystrophy

Myotonic dystrophy is an inherited muscular dystrophy causing muscle weakness and wasting. Many people with myotonic dystrophy complain about excessive daytime sleepiness. This symptom is related to disordered central respiratory control. Psychostimulants are drugs that increase alertness and include caffeine, amphetamine, selegiline, methylphenidate and modafinil. In this updated review there were few randomized controlled trials which evaluated the efficacy and safety of psychostimulants in myotonic dystrophy. One randomized controlled trial of selegiline involving 11 participants did not demonstrate any benefit. Four studies of another drug modafinil suggested inconsistent and slight benefits. Only two of these studies used the gold standard test, a sleepiness scale, to evaluate hypersomnia and found non significant improvement. In these four studies modafinil seemed well tolerated. Further randomized trials are needed to determine the utility of psychostimulants for myotonic dystrophy.

Authors' conclusions: 

There is low quality evidence from two small trials that psychostimulants do not significantly improve the maintenance of wakefulness test in myotonic dystrophy. There is low quality evidence from four studies that modafinil significantly improves the Epworth Sleepiness Scale. More randomized trials are needed to evaluate the efficacy and safety of psychostimulants.

Read the full abstract...
Background: 

Excessive daytime sleepiness is a common symptom of myotonic dystrophy. Psychostimulants are drugs increasingly used to treat hypersomnia in myotonic dystrophy.

Objectives: 

To search systematically for, and combine all evidence from, randomized trials relating to the effects of psychostimulants in myotonic dystrophy patients with hypersomnia.

Search strategy: 

We searched the Cochrane Neuromuscular Disease Specialized Register (October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (19 October 2010, issue 4, 2010 in the Cochrane Library), MEDLINE (January 1966 to October 2010) and EMBASE (January 1980 to October 2010) for randomized trials concerning psychostimulants in myotonic dystrophy, checked the bibliographies of identified papers and made enquiries of the authors of the papers.

Selection criteria: 

We considered all randomized or quasi-randomized trials that have evaluated any type of psychostimulant (versus a placebo or no treatment) in children or adults with proven myotonic dystrophy and hypersomnia.

Data collection and analysis: 

Potentially relevant papers were scrutinized by two authors and the selection of eligible studies was agreed by them and a third author. Data were extracted by one author and checked by a second author.

Main results: 

Primary outcome
Mean improvement in the maintenance of wakefulness test was available for two of the five identified trials accounting for 48 participants. The mean difference +2.52(95% confidence interval (CI) -2.32 to +7.37), was not significant and there was marked heterogeneity across these studies (I2= 50%).

Secondary outcomes
Mean improvement in the Epworth Sleepiness Scale was available in four trials accounting for 101 participants. The mean difference was -2.26 (95% CI -3.78to -0.73), significantly in favor of modafinil with marked heterogeneity across the studies (I2= 84%). There was no evidence for any treatment benefit on the multiple sleep latency test or quality of life.