SYMPOSIA

Abstracts of the Invited Speakers
Hypersomnias and the effects of vigilance-promoting compounds
Antigone Papavasiliou
Department of Neurology, Pendeli Children’s Hospital
E-mail: theon@otenet.gr
Hypersomnia is characterized by a propensity to fall asleep in situations when one is expected to be awake and alert. It may present with
prolonged sleep episodes coupled with excessive daytime sleepiness (EDS) and frequent napping. It is described in narcolepsy, a neurological
disorder characterized by EDS occurring with or without cataplexy; in idiopathic hypersomnia, also of central origin, characterized by EDS
and episodes of prolonged nocturnal sleep; in recurrent hypersomnias, rare disorders manifesting with recurrent episodes of more or
less continuous sleep (average duration of 1 week), recurring at highly variable intervals (one to several months), such as, Kleine–Levin
syndrome and menstrual-related hypersomnia. Chronic sleep loss and/or poor sleep quality may be underlying reasons for EDS; these occur
in numerous sleep disorders, such as obstructive sleep apnea (OSA) and in psychiatric disorders, particularly depression. Approximately
80% of depressive states are associated with insomnia; patients do not necessarily have a higher propensity to fall asleep in daytime but
report subjective sleepiness that differs from the EDS encountered in narcolepsy and OSA. There are also hypersomnias attributable to other
medical conditions, drugs, or substances, as well as behaviorally induced hypersomnia caused by insufficient time to sleep.
Transition between sleep and wakefulness is simply described as oscillations between two opponent processes, one promoting sleep,
another promoting wakefulness. The complex neurobiological mechanisms and the neurotransmitters and neuromodulators underlying
these processes, including noradrenergic, serotonergic, cholinergic, adenosinergic, and histaminergic systems and more recently, the
hypocretin/orexin and dopamine systems, have been established. The mechanisms of action of some vigilance-promoting agents are as
follows: psychostimulants act through enhanced dopamine action (amphetamines, methylphenidate) or acetylcholine action (caffeine);
modafinil may act through enhanced central histamine, hypocretin, and possibly dopamine action; γ -hydroxybutyrate (GHB), acts on GABA
and GHB receptors. EDS in narcolepsy is traditionally treated with psychostimulants; these are rarely effective in idiopathic hypersomnia,
although this was not examined through randomized controlled trials. Modafinil, a first-line wakefulness-promoting medication, is a
useful alternative to psychostimulants for EDS in narcolepsy (Level I evidence). It may be effective for EDS due to idiopathic hypersomnia
(one Level IV study and expert consensus). It is not associated with rebound hypersomnolence, cardiovascular problems, or abuse
potential, as may be seen with amphetamines. Modafinil alleviates sleepiness and fatigue in shift work disorders, residual sleepiness in
treated sleep apnea syndrome, multiple sclerosis, Parkinson’s disease and depression. It is promising as an alternative to psychostimulants
for excessive fatigue associated with medical and psychiatric disorders and as an augmentation medication for treatment-resistant
depression. Due to rare serious complications (allergic and psychiatric), the EMA concluded that its benefit/risk balance was positive for
narcolepsy but negative for other sleep disorders and neurological diseases, including idiopathic hypersomnia. The FDA has approved it
for EDS in narcolepsy, shift work sleep disorder, and OSA. In narcolepsy, GHB at bedtime reduces nocturnal awakenings, increases stage
3 and 4 sleep, and consolidates REM sleep periods; these effects coincide with improvement in daytime symptoms, including cataplexy.
Key words: Vigilance-promoting agents, hypersomnia, psychostimulants, modafinil, γ -hydroxybutyrate
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S44
[JS-04]
The International Union of Basic and Clinical Pharmacology (IUPHAR)
Symposium title: Pharmacogenomics of psychoactive drugs
Role of polymorphic drug transporter in treatment-resistant depression
Tanja Brueckl, M. Uhr
Max Planck Institute of Psychiatry, Germany
E-mail: brueckl@mpipsykl.mpg.de
To be effective antidepressants and other centrally acting drugs have to penetrate the blood-brain barrier. Transport proteins such as
p-glycoprotein that are located at the BBB do not only transport toxic substances but also many drugs back into the blood. In preclinical
animal models and a study examining more than 400 patients, the relationship between polymorphisms in the ABCB1 gene coding
for p-glycoprotein and the clinical efficacy of antidepressants could be demonstrated. With respect to those antidepressants that are
S44 Bulletin of Clinical Psychopharmacology, Vol: 21, Supplement: 2, 2011 - www.psikofarmakoloji.org