Medication strategies in first episode psychosis patients:A survey among psychiatrists

Aim There is an ongoing debate regarding the optimal timing of discontinuation of antipsychotic drugs for patients with first episode psychosis. Although most guidelines recommend maintenance therapy for at least 1 or 2 years after reaching remission, study results indicate that early discontinuation may be beneficial for at least a subsample of patients. To date, little is known about which medication strategies are applied in patients recovering from a first psychotic episode. In this study, we examined the beliefs and practices of clinicians on medication discontinuation. Methods We performed a survey among 50 experienced Dutch psychiatrists to assess how often specific treatment strategies have been applied in the past 12 months, as well as their knowledge and expectations with respect to medication discontinuation. Results Psychiatrists estimated that, after remission, they continued medication at the same dose for at least 12 months in 51.2% of cases, continued in a reduced dose in 33.8% of cases and discontinued medication in 9.1% of cases after 4.4 months of remission on average. Although the medication is discontinued in only a relatively small proportion of patients, almost half of all clinicians (45.9%) used this strategy at least once in the past 12 months. Conclusions There is substantial practice variation in antipsychotic medication strategies after remission from a first psychotic episode. Future research on long-term effects of early medication discontinuation can guide clinicians in making evidence-based decisions when treating first-episode patients

Preventive cognitive therapy versus treatment as usual in preventing recurrence of depression:Protocol of a multi-centered randomized controlled trial

Background Major depressive disorder (MDD) is projected to rank second on a list of 15 major diseases in terms of burden in 2030. The contribution of MDD to disability and health care costs is largely due to its highly recurrent nature. Therefore, part of the efforts to reduce the disabling effects of depression should focus on preventing recurrence, especially in patients at high risk of recurrence. The best established effective psychological intervention is cognitive therapy, with indications for prophylactic effects after remission. Methods/Design In this randomized controlled trial (cost-) effectiveness of Preventive Cognitive Therapy (PCT) after response to Acute Cognitive Therapy (A-CT) will be evaluated in comparison with Treatment As Usual (TAU). Remitted patients that responded to A-CT treatment with at least two previous depressive episodes will be recruited. Randomization will be stratified for number of previous episodes. Follow-ups are at 3, 6, 12 and 15 months. The primary outcome measure will be the time to relapse or recurrence of depression meeting DSM-IV criteria for a major depressive episode on the Structured Clinical Interview for DSM-VI Axis I Disorders (SCID-I). Costs will be measured from a societal perspective. Discussion This study is the first to examine the addition of PCT to TAU, compared to TAU alone in patients that recovered from depressive disorder with A-CT. Alongside this effect study a cost effectiveness analysis will be conducted. Furthermore, the study explores potential moderators to examine what works for whom. Trial registration Netherlands Trial Register (NTR): 2599, date of registration: 11-11-2010. Keywords Depression Relapse Recurrence Cognitive Therapy Preventio

Effect of Terbinafine on the Pharmacokinetics of Cyclosporin in Humans

Cyclosporin is largely metabolized by hepatic cytochrome P450 enzymes, and azole drugs that inhibit cytochrome P450 may precipitate cyclosporin toxicity. The allylamine terbinafine binds to a small subfraction of hepatic cytochrome P450 in type I fashion, and has no effect upon hepatic metabolism of cyclosporin in vitro. The purpose of this study was to determine whether oral terbinafine alters the pharmacokinetics of oral cyclosporin in vivo.Twenty male volunteers (age 19–44 years), were randomly allocated to two groups. The first group received three single oral doses of cyclosporin 300mg at intervals of 21 d. The second and third doses of cyclosporin were preceded by a 6-d course of oral terbinafine 250mg each morning. A further 250mg of terbinafine was taken with the second and third doses of cyclosporin. Blood levels of cyclosporin and terbinafine were monitored for 36h after each dose. The second group received a 7-d course of terbinafine 250mg each morning. On the seventh day a single dose of cyclosporin 300mg was taken together with the terbinafine. Blood levels of both cyclosporin and terbinafine were monitored for 36kh. Two further single doses of cyclosporin 300mg were given at intervals of 2 weeks and the cyclosporin levels again monitored. In both groups each cyclosporin dose was preceded by an 8-h fast.The mean peak blood concentration of cyclosporin when taken alone was 958 μg/I, and 822 when taken with terbinafine. The mean area under the curve for cyclosporin was 4207 μg/l/h when taken alone and 3665 when taken with terbinafine. The mean absorption half-life for cyclosporin when taken alone was 0.29 h, and 0.33 when taken with terbinafine. The mean time of maximum concentration and elimination half-life of cyclosporin were unaltered by terbinafine. The results suggest that terbinafine is likely to prove a safe systemic anti-fungal treatment for patients who are taking cyclosporin

Victimization of patients with severe psychiatric disorders: prevalence, risk factors, protective factors and consequences for mental health. A longitudinal study

<p>Abstract</p> <p>Background</p> <p>Victimization among people with a Severe Mental Illness is a common phenomenon. The objectives of this study proposal are: to delineate the extent and kind of victimization in a representative sample of chronic psychiatric patients; to contribute to the development and validation of a set of instruments registering victimization of psychiatric patients; to determine risk factors and protective factors; and to gain insight into the possible consequences of victimization.</p> <p>Methods/Design</p> <p>An extensive data set of 323 patients with Sever Mental Illness (assessed 4 years ago) is used. In 2010 a second measurement will be performed, enabling longitudinal research on the predictors and consequences of victimization.</p> <p>Discussion</p> <p>The consequences of (re)victimization have barely been subjected to analysis, partially due to the lack of a comprehensive, conceptual model for victimization. This research project will contribute significantly to the scientific development of the conceptual model of victimization in chronic psychiatric patients.</p

Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis

BACKGROUND: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. METHODS: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. RESULTS: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. CONCLUSIONS: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes

Usutu virus NS4A suppresses the host interferon response by disrupting MAVS signaling

Usutu virus (USUV) is an emerging flavivirus that can infect birds and mammals. In humans, in severe cases, it may cause neuroinvasive disease. The innate immune system, and in particular the interferon response, functions as the important first line of defense against invading pathogens such as USUV. Many, if not all, viruses have developed mechanisms to suppress and/or evade the interferon response in order to facilitate their replication. The ability of USUV to antagonize the interferon response has so far remained largely unexplored. Using dual-luciferase reporter assays we observed that multiple of the USUV nonstructural (NS) proteins were involved in suppressing IFN-β production and signaling. In particular NS4A was very effective at suppressing IFN-β production. We found that NS4A interacted with the mitochondrial antiviral signaling protein (MAVS) and thereby blocked its interaction with melanoma differentiation-associated protein 5 (MDA5), resulting in reduced IFN-β production. The TM1 domain of NS4A was found to be essential for binding to MAVS. By screening a panel of flavivirus NS4A proteins we found that the interaction of NS4A with MAVS is conserved among flaviviruses. The increased understanding of the role of NS4A in flavivirus immune evasion could aid the development of vaccines and therapeutic strategies