Newsletters.no

Azilect nyhetsbrev nr 3
Vel overstått sommerferie!
“Treatment decisions in newly
diagnosed Parkinson’s disease”
Vel tilbake på arbeid venter pasienter, kolleger og legemiddelindustrien på din tid betydningsfull i kraft av din kompetanse og hos den enkelte pasient er så forskjellig, Det er selvfølgelig individuelt, men noen bør man tenke på ved valg av behandling fellestrekk er det. Et av dem er å delta på for å få riktig balanse mellom reduserte internasjonale kongresser. EFNS er nettopp nevrologer fra hele verden var samlet for å annen side? Dette er beslutninger som har høre, se, presentere og diskutere nye funn En oase for den vitebegjærlige, og en utstillingsplass for forskeren. Norge har både absolutt og relativt vært blant de største deltagerlandene, men ikke i år 2012. Norsk deltagelse er nærmest “When monotherapy becomes
halvert fra 2011, og det til tross for at suboptimal”
kongressen ble arrangert i vårt naboland. Dersom dette har sammenheng med at legemiddelindustrien ikke lenger organiserer og sponser norske leger, håper jeg både for arbeidsgivere kjenner sin besøkelsestid! under EFNS i Stockholm i september. Han forklarer både mekanismer som er involvert i wearing-off, og mulige strategier for å redusere problemet. Jenner Vel møtt på neste kongress!
poengterer at optimal dopaminerg kontroll allerede tidlig i sykdomsforløpet av Parkinsons sykdom er viktig. Abstraktet Vil du ikke motta nyhetsbrev i fremtiden klikk her for å melde deg av
Treatment decisions in newly diagnosed Parkinson’s disease
Werner Poewe

Abstract
Parkinson’s disease (PD) stands out among the neurodegenerative diseases by the availability of highly efficacious symptomatic therapies. Treatment decisions in newly diagnosed patients with PD are nevertheless complex and involve multiple patient-related and drug-related factors. Types and severity of presenting symptoms may differ markedly between patients. Age and individual risk profiles for drug-related side effects, as well as personal needs and perceptions, all have to be factored in, when deciding how to best initiate therapy. There may also be a question if treatment should be initiated immediately following diagnosis or not. Whether or not early treatment can favourably influence disease clinical progression remains an open question, although several experimental and clinical lines of evidence suggest that early monotherapy may be associated with better functional outcomes compared to delayed treatment. Placebo-controlled drug trials in early PD have shown that UPDRS scores in early PD decline by 6–14 points/year and the ADAGIO study has shown that, even in patients with very early and mild disease, significant treatment effects can be detected with MAO-B inhibition alone. Deciding on which drug to use for which patient always involves careful consideration of expected efficacy versus side effect risk, as well as ease-of-use and compliance. At present, there is a choice of three main categories of monotherapy for newly diagnosed patients – levodopa, a dopamine agonist (DA), or an MAO-B inhibitor. Levodopa is efficacious in the control of motor symptoms, and has good tolerability. However, the risk of motor complications with increasing dose levels and treatment duration (particularly in younger patients), as well as the need for multiple daily dosing, are all notable disadvantages. As for the DAs, their efficacy against motor symptoms and in delaying dyskinesias is well established, but the association with daytime somnolence, and impulse control disorders (ICDs), may limit their use. Rasagiline has also displayed significant efficacy in monotherapy with impact on the motor and non-motor symptoms of PD, and on activities of daily living (ADLs), from the very early stages of disease. Moreover, it offers a favourable tolerability profile even in the older age groups, and a convenient once-daily dosing. Therefore, treatment decisions in newly diagnosed PD must be carefully considered in order to create the right balance for each patient, by improving symptoms and ADLs, minimising tolerability issues, and thereby maintaining QoL. When monotherapy becomes suboptimal
Peter Jenner

Abstract
Over a period of years, most patients who receive monotherapy for Parkinson’s disease (PD) will experience a decline in their response to treatment, known as ‘wearing-off’. Wearing-off is a typical response to a potent but short-acting agent, in which symptoms begin to return prior to the next dose of treatment. In PD, patients may not only experience the return of cardinal motor symptoms, but also non-motor signs including pain, fatigue, and mood changes which may precede the return of motor symptoms. Recent studies have revealed that wearing-off occurs much earlier in the disease course than previously thought – affecting almost 50% of patients between 1–2 years after the initiation of levodopa. In the ELLDOPA study, fluctuations were detected even earlier, with symptom re-emergence observed within 5–6 months. However, although wearing-off is acknowledged as the biggest challenge of levodopa therapy, it has also been observed with dopamine agonist treatment. In terms of underlying mechanisms, wearing-off is caused by a combination of disease pathology and drug-related effects. It has been suggested that post-synaptic changes in the mediation of striatal receptor and intercellular activity, and functional abnormalities in basal ganglia output pathways, are involved. In PD, these post-synaptic changes may create compensatory mechanisms in response to the depletion of pre-synaptic dopamine, and thereby modulate the output of the basal ganglia. However, the addition of drugs to supply pulsatile dopamine stimulation may compromise this compensatory activity. Experiments also indicate that preservation of the tonic dopaminergic stimulation of post-synaptic receptors (as opposed to phasic stimulation) is important in restoring the normal physiological function of the basal ganglia, and preventing the onset of wearing-off. In the drive to retain this physiological state for as long as possible, strategies have been employed to prolong and stabilise the activity of levodopa. In addition, therapy with MAO-B inhibitors (which are irreversible and, therefore, non-pulsatile) prevents the breakdown of endogenous and exogenous dopamine, and thereby brings dopaminergic transmission towards its normal, physiological level. In terms of clinical relevance, early wearing-off may be one of the most important indicators that a patient with PD is entering a more complex stage of the disease. Therefore, ensuring that the currently available treatments achieve optimal dopaminergic control as early as possible in the disease course is an important consideration.

Source: http://www.newsletters.no/sites/default/files/pdf/archive/Azilect%20NL%203.pdf