When people with ME/CFS say they’re not the same person they used to be, it’s not just physical illness they’re talking about it; for many the ‘mental component’; the loss of sharpness, of focus, of the ‘cognitive grace’ they used to experience can be difficult. Losing or altering such intimate parts of who we consider ourselves can be challenging to say the least.
So when something shows up that may reverse some of the ‘brain drain’ it’s interesting. Brain stimulants are used (or at least tried) fairly regularly in chronic fatigue syndrome but few studies have examined their effects. Now a rare placebo-controlled double-blinded trial suggests a new and less addictive type of amphetamine called lisdexamfetamine dimesylate or Vyvanse, could work for some patients.
Amphetamines increase energy levels, enhance concentration and motivation and tend to boost the ‘reward’ centers of the brain. As such they’ve been used legally and illegally to boost performance in many sectors of society including the military, athletes and by college students cramming for exams.
Paul Erdos, one of the greatest mathematicians of the 20th century, claimed he lost a month of work after quitting amphetamines for a month to win a bet, saying “Before, when I looked at a piece of blank paper my mind was filled with ideas. Now all I see is a blank piece of paper.” It’s no wonder, given their cognitive challenges and depleted energy levels, that many people with ME/CFS give them a try…
Problems with physical and psychological dependence, however, have lead amphetamines to be classified as Schedule II drugs which have a high potential for abuse.
Approved for use in ADHD, Vyvanse is being studied in depression, multiple sclerosis, menopause, excessive daytime sleep, traumatic brain injury, addiction, and binge eating. ADHD may be common in both fibromyalgia and ME/CFS (Saez-Frances et. al. 2012).
Vyvanse affects executive functioning, which studies suggests in impaired in chronic fatigue syndrome. Executive functioning is needed for planning or decision-making (ach!) or when we’re faced with novel situations. If your ability to plan or make decisions took a hit, or if you’ve had more trouble overcoming temptations, or if you feel you’ve become locked into habitual responses since you came down with this disorder, then poor executive decision making may be to blame.
The ME/CFS patients in the study had documented problems with executive functioning and over 60% of them also scored above the threshold for ADHD on the ADHD-RS test.
Less confusion, better decision making, more mental alertness, etc. would be a nice thing to have. Let’s see how they did on Vyvanse.
The participants took from 30 to 50 to 70 mgs/day of the drug or placebo for six weeks. The Behavior Rating Inventory of Executive Function-Adult ( Brief-A) test was used to measure working memory, planning and organizational ability, emotional control, etc. People with a wide variety of disorders ranging from ADHD to autism to multiple sclerosis to depression have abnormal results on this test.
The results were positive with ME/CFS patients on the drug scoring significantly higher (p<.005) on the Brief-A test. Interestingly, but perhaps not surprisingly, given the growing recognition that poor cognition effects more than the mind, the people on the drug also experienced significantly less fatigue and less pain. The researchers stated…
“the present study demonstrates that (Vyvanse) is safe and well tolerated among participants with both CFS and clinically signiﬁcant executive functioning deﬁcits. Although it does not appear to be curative, further studies should be undertaken to assess the rate of relapse following cessation of treatment. Observations in the clinic thus far suggest the beneﬁts are sustained only with ongoing treatment.”
The finding that the drug improved cognition and resulted in less fatigue and pain was intriguing. Nobody knows exactly why a psychostimulant should be able to relieve pain but the theory is that improved cognition may be enhance a person’s ability to filter out pain sensations.
This idea that cognitive ‘weakness’ could result in pain signals being magnified or less well controlled, or on the flip side, that increasing one’s cognitive ‘strength’ could enhance one’s ability to reduce pain levels is appealing. Meditators, after all, have been shown to have a higher tolerance to pain probably because they are able to blunt the emotional response to pain, which turns on the fight/flight response, which in turn increases pain levels.
Executive Functioning and the Prefrontal Cortex
The prefrontal cortex (PFC) could be a key player in this scenario. The PFC, which sits in the front, top region of the brain, has long been known as the source of high-level cognitive thought. The PFC, for instance, is supposed to tame the ‘cruder’, more automatic reactions of the fear center of the brain, the amygdala, and keep it from over-reacting. Amygdala activation is tied not just to fear and the activation of the fight/flight response but also playsrole in pain production.
Some evidence suggests the prefrontal cortex may not be working particularly well in chronic fatigue syndrome. If the PFC is too weak to control the amygdala then a drug that could strengthen PFS functioning could quiet down the amygdala and conceivably reduce pain and fatigue levels as well.
Intriguingly, Vyvanse regulates both sympathetic nervous system (noradrenergic) and dopamine activity in the prefrontal cortex. Dopamine levels are typically low in ADD and ADHD (and ME/CFS?) and can effect not just concentration but interestingly enough, another issue in ME/CFS - muscle control and coordination. Could Vyvanse’s effects on the prefrontal cortex be smoothing out an overheated and over-reactive system?
This was a very small study – just 26 people, half of whom got the drug but hopefully we’ll get larger studies in the future.
Vyvanse is a next generation amphetamine which promises fewer side effects than other amphetamines but the list of ‘common’ side effects (>5% in frequency) is a long one and includes dizziness, agitation, nausea, anxiety, diarrhea, weight loss, euphoria, rapid heartbeat and severe side effects can include tachycardia, fever, muscle tremors, seizures, etc. The authors reported few side effects in the small CFS population tested.
Use of lixdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: A double blind, placebo-controlled study. Psychiatry Res. 2012 Oct 9. pii: S0165-1781(12)00503-3. doi: 10.1016/j.psychres.2012.09.007.
Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients. Sáez-Francàs N, Alegre J, Calvo N, Antonio Ramos-Quiroga J, Ruiz E, Hernández-Vara J, Casas M. Psychiatry Res. 2012 May 28
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