Trying to Remedy Unrefreshing Sleep in ME Source: http://findanswerstome.blogspot.co.uk/2012/07/trying-to-remedy-unrefreshing-sleep-in.html This is just a quick post I will follow up with further links to studies when I have the time. Things that can help some people with the paralyzing feeling left over from unrefreshing sleep. I have found that Pregabalin 300mg can increased Slow Wave Sleep Stages 3&4. Also 5HT2a antagonists such as Risperidone inhibit only 5HT2a receptors at low doses (i.e. 0.5mg) a higher dose will cause side effects and not as selectively target the 5HT2a receptor and thus inhibit other receptors such as D2 etc. I have found that Pregabalin 300mg combined with Risperidone 0.5 give the best results for reducing that dreadful feeling where you wake up feeling like you've had a seizure - like your head's been kicked around like a football (aka unrefreshing sleep). Take these an hour before you go to bed - you may need to use them in conjunction with a sedative med like low dose doxepin 6-10mg that does not interfere with deep sleep. I use this to get me to sleep. I would not use any benzodiazepines in conjunction with these deep sleep meds because benzos will reduces Stages 3&4 sleep. Zopiclone, zolpidem etc are okay because they do not reduce SWS. In the near future more potent deep sleep inducing medications will become available in the form of 5HT2a inverse agonists such as Ketanserin. These could provide a safer alternative to Sodium Oxybate (Xyrem). I have to say though unfortunately I seem to build tolerance to almost all medications and hence I would recommend to administer these drugs in a cyclical fashion, rotating them frequently or if an alternative is not available, coming off them for several days before going back on. This should reduce receptor downregulation to some extent.