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