WT and JNK1 2/2 mice were challenged with adenovirus expressing IL-17A for three days

a constant upward trend when its patent expired in 2003. Contrary to citalopram, paroxetine use dropped in February 2002, the same year that its patent status expired, and prior to the first period of increased media coverage and regulatory warnings. Most of the negative media coverage was directed towards paroxetine in both the NL and UK. In 2001, GlaxoSmithKline lost its first lawsuit concerning paroxetine’s association with murder and suicide, and this resulted in a FDA product warning. In 2002, the BBC aired a documentary `The Secrets of Seroxat’ that highlighted safety concerns about this product, both in terms of suicidality and difficulties with discontinuing use. These series of events may have induced the plunge in paroxetine use in the UK observed in our results prior to the first period of media coverage of regulatory warnings, in February 2002. Specific SSRI use in the NL was comparable with the UK to a limited extent. Citalopram, escitalopram, and sertraline use also showed upward trends in the period under survey, albeit with limited signs of diminished use towards the end of the survey period and after the periods of media coverage of regulatory warnings. The Dutch GP guideline for the treatment of depression in adults recommends either a TCA or an SSRI as first-line treatment, giving priority to fluvoxamine, paroxetine, sertraline and a lower priority to fluoxetine due to the long-half life. Remarkably, individual SSRIs with a large market uptake and a positive benefit/risk profile, such as citalopram and escitalopram are not mentioned, nor recommended in the Dutch guidelines. The Dutch guideline for specialists extensively considers the benefits and risks of citalopram and escitalopram. The preference for paroxetine in GP guidelines may be one of many factors why its use was less affected in the NL by media coverage of regulatory warnings compared to the UK where citalopram, escitalopram, and fluoxetine are recommended for GP use. Most of the SSRI prescriptions in the NL were issued by a GP, confirming previous research. Dutch GPs and specialists started prescribing less paroxetine towards the end of the first period of media coverage of regulatory warnings, apparently indicating a timely reaction from prescribers to the regulatory advisories or media attention. On the other hand, the increasing prescription rate of citalopram by both Dutch GPs and specialists demonstrated little or no effect during both periods of media coverage of regulatory warnings, as well as either prescribers’ disregard of the regulatory warnings or switching. The influence of guidelines, reimbursement policies, and prescribing habits for SSRI use should be further studied to better understand the differences for specific SSRIs and between countries. Notwithstanding the modest reduction in paroxetine use in the NL, we measured MGCD516 biological activity significant drops in use for pediatrics, adolescents, and young adults prior to the period of media coverage of regulatory warnings. Therefore, no direct association between the periods of media coverage of regulatory warnings and decreased paroxetine use was found in young groups. Conversely, both periods of media coverage of regulatory warning were associated with decreased paroxetine use in adults and elderly, although the warnings were originally not thought to affect these age groups. Presumably, disadvantages regarding the use of paroxetine, such as the high risk of withdrawal effects or akathisia, could have caused