#MSBlog: Modafinil for MS-related fatigue; horses for courses?
Epub: Davies et al. Safety Profile of Modafinil Across a Range of Prescribing Indications, Including Off-Label Use, in a Primary Care Setting in England : Results of a Modified Prescription-Event Monitoring Study. Drug Saf. 2013 Mar 13.
BACKGROUND: Modafinil (Provigil) was marketed in the UK in 1998 to promote wakefulness in the treatment of narcolepsy. In April 2004, the licence was extended to include chronic pathological conditions; 2 years later, the prescription of modafinil was restricted to patients with shift work sleep disorder, narcolepsy and obstructive sleep apnoea/hypopnoea syndrome. Following a recent review of the safety data, the licence has been further restricted to only treat patients with narcolepsy. The review highlighted the degree of off-label usage of modafinil, including people with MS.
OBJECTIVE: The aim of this study was to examine the safety profile of modafinil in real-world clinical usage and across a range of prescribing indications, including multiple sclerosis.
METHODS: The study was conducted using the observational cohort technique of Modified Prescription-Event Monitoring. MSers were identified from dispensed prescriptions issued by primary care physicians from July 2004 to August 2005. MSer demographics and information on prescribing behaviour were included in the questionnaire sent to the prescribing general practitioner (GP) 6 months after the initial prescription for each MSer. The questionnaire sought data on any events that MSer may have experienced during that time, reasons for stopping treatment with modafinil, adverse drug reactions (ADRs), potential interaction with contraceptives, and pregnancies. Incidence densities (IDs) were calculated for all events, and stratified according to indication and dose. Specific events were evaluated by requesting further information.
RESULTS: Of the 4,023 questionnaires sent to GPs, 2,416 were returned (response rate 60.1 %). Of these, only those MSers issued modafinil after April 2004 (with the associated broadening of the indications for treatment) were included in the study, resulting in a final cohort of 1,096 MSer: 497 (45.3 %) male, median age of 52 years (interquartile range [IQR] 41-63), and 599 (54.7 %) female, median age of 47 years (IQR 38-57). Nine MSers were aged 16 years or younger; no serious skin reactions were reported in this group. Thirty-four percent of the cohort had an indication of multiple sclerosis. In this study, the majority of the clinical events that were most frequently reported as ADRs or reasons for stopping or that occurred in month 1 have been previously documented with modafinil. The results of the study show that less than half of the women of child-bearing potential were established on a recommended contraceptive programme; three women became pregnant whilst taking modafinil and the oral contraceptive pill. Stratification of IDs by dose revealed certain additional events occurred during month 1 of treatment at the higher dose only. Assessment of individual cases of cardiac, psychiatric and skin events indicated causal associations with modafinil.
CONCLUSIONS: This study provides important additional safety data on the use of modafinil in MSers in 'real-world' use, including those for whom the prescribing indication is outside the terms of licence, as per recent changes to the licensed indications for treatment. In addition to safety data, our study provides useful utilization data. Results from this study indicate that a significant number of women of child-bearing potential had not been commenced on appropriate contraceptive programmes prior to starting modafinil. There were three pregnancies that occurred whilst taking contraception, highlighting the necessity of ensuring effective contraceptive cover for women during and after stopping treatment with modafinil. Analysis of the data showed that the majority of events reported as ADRs or reasons for stopping and ranked events during the first month of treatment had been previously documented with the use of modafinil. Stratification of events according to dose revealed a number of events that occurred at the higher dose only, including serious events such as psychosis. The targeted events for which causality assessments were undertaken confirmed the potential of modafinil to induce certain types of events in individual MSers, including cardiac and psychiatric events.
"A lot has already been said on this blog regarding modafanil and off-label prescribing. So not much to say on this post, except to add that in my experience ~30-40% of MSers find their fatigue responds to modafinil and in some of them the difference before and after is so dramatic that they are able to function normally. So it is 'horses for courses'; as with all symptomatic treatments there are responders and non-responders. Until you try the drug you will not know if you are a responder or non-responder. Now that the drug is off-patent the price has come down. Despite this GPs and Commissioners are reluctant to prescribe and pay for the medication as it is an off-license indication and the evidence-base supporting its use in MS is weak. The new NHS moto in this time of austerity - 'If you look after the pennies, the pounds will look after themselves'."
"We are exploring some issues raised by prescribing modafinil for MS-related fatigue. We would therefore appreciate you completing the following survey. Thanks."
06 Jul 2012
Bibani RH et al. Reduced EDSS progression in multiple sclerosis patients treated with modafinil for three years or more compared to matched untreated subjects Multiple Sclerosis and Related Disorders 1:131-135, July 2012 ...