OBJECTIVES: Major Depressive Disorder (MDD) is an important and growing health problem in Turkey. Inclusion of a new drug in the positive list for its treatment requires the proof of cost effectiveness. The objective of this study was to assess the cost effectiveness of Agomelatine versus Venlafaxine and Duloxetine in treatment of MDD in Turkey. The study was undertaken from the payer perspective. METHODS: A discrete event model, already validated by European health authorities was used to compare Agomelatine with Venlafaxine and Duloxetine. An indirect comparison was made between Agomelatine and Duloxetine. In order to reflect the real clinical practice, the model defined 3-6 months of treatment, however the maintenance phase, defined as the recommended time to prevent eventual recurrences, was modeled longer (12 weeks and 24 weeks).The clinical outcome was measured as life years in remission. All direct costs for the year 2011 were taken into account. Costs and benefits were discounted by 3% and robustness of the results were tested by Monte Carlo simulation. RESULTS: Incremental Cost Effectiveness Ratios(ICER) were calculated and results were displayed as cost per additional life year in remission. The ICER was calculated as -18,799 TL/year in remission for Agomelatine versus Venlafaxine and -27,453 TL/year in remission for Agomelatine versus Duloxetine. CONCLUSIONS: Agomelatine dominated Venlafaxine and Duloxetine in treatment of MDD in Turkey. Sensitivity analyses revealed that the results were robust.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children, with worldwide prevalence of ADHD varying from 5.9 to 7.1 %, depending on the reporter. In case of inadequate response to stimulants, combination therapy of stimulants and an adjunctive medication may improve the control of ADHD symptoms, reduce the dose-limiting adverse events, and help control comorbidities. To date, the only medication to be used for adjunctive therapy to psychostimulants is guanfacine extended release (GXR). The aim of this study was to assess the economic impact of GXR as an adjunct therapy with long-acting stimulants (GXR + stimulant) compared to long-acting stimulant monotherapy (stimulant alone) in the treatment of children and adolescents with ADHD in Canada.MethodA Markov model was developed using health states defined based on the clinician-reported Clinical Global Impression-Severity (CGI-S) score (normal, mild, moderate, severe). Transition probabilities were calculated based on patient-level data from a published study. Long-acting stimulants available in Canada were considered in the base-case model: amphetamine mixed salts, methylphenidate HCl formulations, and lisdexamfetamine dimesylate. Analyses were conducted from a Canadian Ministry of Health (MoH; Ontario) and a societal perspective over a 1-year time horizon with weekly cycles.ResultsOver a 1-year time horizon, GXR + stimulant was associated with 0.655 quality-adjusted life year (QALY), compared to 0.627 QALY with stimulant alone, for a gain of 0.028 QALY. From a MoH perspective, GXR+ stimulant and stimulant alone were associated with total costs of $CA1,617 and $CA949, respectively (difference of $CA668), which resulted in an incremental cost-effectiveness ratio (ICER) of $CA23,720/QALY. From a societal perspective, GXR + stimulant and stimulant alone were associated with total costs of $CA3,915 and $CA3,582, respectively (difference of $CA334), which resulted in an ICER of $CA11,845/QALY. Probabilistic sensitivity analysis (PSA) of GXR + stimulant showed that it remains a cost-effective strategy in 100 % of the simulations from both perspectives in numerous PSA and one-way sensitivity analyses, relative to a willingness to pay threshold of $50,000/QALY.ConclusionsThis economic evaluation demonstrates that GXR + stimulant is cost-effective compared to stimulant alone in the treatment of children and adolescents with ADHD in Canada.

L-type prostaglandin synthase (L-PGDS) produces PGDProstaglandins (PGs) 5 are lipid mediators formed from arachidonic acid through the action of cyclooxygenases (COXs). COXs convert arachidonic acid released from the plasma membrane to an intermediate substrate, PGH 2 , which is metabolized by specific synthases to produce PGs like PGD 2 (1, 2). PGD 2 is involved in various physiological processes such as vasodilatation, bronchoconstriction (3), regulation of pain (4), and sleep (5) but is also implicated in inflammatory responses such as asthma (6) and atherosclerosis (7). PGD 2 was shown to exhibit anti-inflammatory properties as well, as increased levels of PGD 2 are observed during the resolution phase of inflammation (8 -10). Recent work by our group showed that PGD 2 displays anabolic properties in bone (11,12).There are two types of prostaglandin D 2 synthase (PGDS). The hematopoietic PGDS (H-PGDS) is glutathione-requiring (13) and is expressed mainly in mast cells (14), megakaryocytes (15), and T-helper 2 lymphocytes (16). The lipocalintype PGDS (L-PGDS), also called ␤-trace, is glutathione-independent and is expressed abundantly in the central nervous system (17, 18), the heart (19), the retina (20), and the genital organs (21). L-PGDS is also the only enzyme among the members of the lipocalin gene family and binds small lipophilic substances like retinoic acid (22), bilirubin (23), and gangliosides (24).The arrestin family consists of ubiquitously expressed arrestin-2 and -3 (also known as ␤-arrestin-1 and -2) and two retinal arrestins (25). Arrestin-2 and -3 are multifunctional molecules in addition to their well known role in desensitization and internalization of G protein-coupled receptors (26). The identification of numerous non-receptor binding partners has expanded their functions to protein ubiquitination, chemotaxis, apoptosis, mitogen-activated protein kinases activation (27, 28), osteoclastogenesis inhibition (29), and regulation of the interleukin 1 (IL-1) pathway (30).It is remarkable how very little is known about the interaction partners and the mechanisms regulating the activity of PG synthases considering their crucial physiological and pathological roles and the clinical problems associated with the long term use of COX inhibitors. Here we show that arrestin-3 interacts with L-PGDS and increases L-PGDS-mediated PGD 2 production. An arrestin-3 peptide was identified as capable of inducing PGD 2 production by L-PGDS. This is important because it shows that by identifying interacting partners of PG synthases we can not only further our understanding of the

BackgroundBipolar disorder (BPD) is prevalent and is associated with a significant economic burden. Asenapine, the first tetracyclic antipsychotic approved in Canada for the treatment of BPD, has shown a comparable efficacy profile to other atypical antipsychotics. In addition, it is associated with a favourable metabolic profile and minimal weight gain potential. This study aimed to assess the economic impact of asenapine compared to olanzapine in the treatment of BPD in Canada.MethodsA decision tree combined with a Markov model was constructed to assess the cost-utility of asenapine compared with olanzapine. The decision tree takes into account the occurrence of extrapyramidal symptoms (EPS), the probability of switching to a different antipsychotic, and the probability of gaining weight. The Markov model takes into account long-term metabolic complications including diabetes, hypertension, coronary heart diseases (CHDs), and stroke. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective over a five-year time horizon with yearly cycles.ResultsIn the treatment of BPD, asenapine is a dominant strategy over olanzapine from both a MoH and a societal perspective. In fact, asenapine is associated with lower costs and more quality-adjusted life years (QALYs). Results of the probabilistic sensitivity analysis indicated that asenapine remains a dominant strategy in 99.2% of the simulations, in both a MoH and a societal perspective, and this result is robust to the many deterministic sensitivity analyses performed.ConclusionsThis economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine in the treatment of BPD in Canada.

Despite the short time horizon, the lack of compliance data and the assumptions made, this economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine and to most of the atypical antipsychotics frequently used in Canada.