Tamar Wohlfarth

HOW NEUROTICISM, LONG-TERM DIFFICULTIES, AND LIFE SITUATION CHANGE INFLUENCE PSYCHOLOGICAL DISTRESS - A LONGITUDINAL MODEL

The causal relationships between neuroticism (N), long-term difficulties (LTDs), life situation change (LSC), and psychological distress (PD) were examined using self-report and interview data from a 7-year, 3-wave study in a general population sample (N = 296). LTDs were classified as either endogenous (dependent) or exogenous (independent). We found that earlier neuroticism had a strong direct and a moderate indirect effect (through endogenous LTDs) on PD. The direct effect was strikingly stronger than those of LTDs and LSC. In addition, much correlation between endogenous LTDs, LSC, and PD could be attributed to the confounding effects of earlier neuroticism. High neuroticism tended to strengthen the effect of LSC on PD. These findings suggest that temperamental dispositions are more powerful than environmental factors in predicting PD.

Screening for Posttraumatic Stress Disorder: an evaluation of two self-report scales among crime victims.

The validity of the Impact of Events Scale (IES) and the Posttraumatic Stress Disorder (PTSD) Symptom Scale, Self-Report version (PSS-SR) was examined among crime victims. Both instruments performed well as screeners for PTSD. For the IES, sensitivity ranged between .93 and 1.00; for the PSS-SR, sensitivity ranged between .80 and .90. Specificity for the IES ranged between .78 and .84 and for the PSS-SR ranged between .84 and .88. Some individual items from the 2 scales performed just as well as the total scales. The authors conclude that either of these short self-report instruments or their individual items are suitable as screeners for PTSD, specifically in settings where mental health professionals are unavailable. Cross-validation of these results is necessary because of the small sample size in this study.

Antidepressants use in children and adolescents and the risk of suicide

OBJECTIVEnAntidepressants use in paediatric patients has been linked with risk of suicidal behaviours. The aim of this paper, therefore, is to examine whether all antidepressants are associated with such risk.nnnMETHODnAll 22 paediatric short-term placebo-controlled trials of SSRIs and NSRIs that were submitted to European registration authorities by pharmaceutical companies were identified and examined for events related to suicidality, which were defined as suicide, suicide attempts or suicidal thoughts. Random effect meta-analysis was used to combine the information from all trials.nnnRESULTSnNo completed suicides were reported. However, for each compound there was at least one study with an increased risk for events related to suicidality in the active compound group. The overall OR for these events in the depression studies was 1.67 (95% CI: 1.05-2.65) and for anxiety 1.33 (95% CI: 0.33-5.35).nnnCONCLUSIONSnCaution is called for in the use of all SSRIs and NSRIs in the paediatric population. Furthermore, in the absence of contradictory information, caution in the use of other antidepressants in this population should be exercised as well (e.g. tricyclic antidepressants).

The EU paediatric regulation: effects on paediatric psychopharmacology in Europe.

Child and adolescent psychiatry is a relatively young field and the recognition, classification, and treatment of disorders in children and adolescents lag behind those in adults. In recent years there is an increasing awareness of the differences between children and adults in psychopathology and pharmacology. Related to this new paediatric regulations have been introduced. This article reviews the regulatory and legislative measures that were adopted in the EU in 2007 and the subsequent impact of these measures on the field of paediatric psychopharmacology. The consequences of the paediatric regulation in the EU are reflected in several domains: regulatory, research aimed at drug development and clinical practices. In the regulatory domain, the consequences include: new paediatric indications, inclusion of special (class) warnings, specification of dose regimens, and information on safety specific to children and adolescents, and development of new medicinal formulations. The paediatric regulation leads to timely development of paediatric friendly formulations and better quality of the clinical evidence. In clinical practices, an increased awareness of the uniqueness of paediatric pharmacology is emerging among medical professionals, and subsequent improvement of medical care (i.e. correct doses, appropriate formulation, monitoring for expected adverse events). In addition, clinical guidelines will have to be revised more frequently in order to integrate the recently acquired knowledge. The new regulations stimulate transparency and discussions between academia, pharmaceutical industry, and regulators. The purpose is to optimize clinical research and obtain evidence for paediatric psychopharmacology, thereby providing adequate support for treatment.

Insomnia medication: Do published studies reflect the complete picture of efficacy and safety?

Selective publication can have a deleterious effect on evidence based medicine, health policy decision making and treatment guidelines. Using the European Public Assessment Reports (EPARs) as reference, this study examined selective publication and selective reporting of efficacy and safety of insomnia medication. EPARs of with three insomnia medications were used to identify all clinical trials that were performed between 1998 and 2007 for the purpose of registration in the EU. The matching publication for each trial was searched through a systematic literature search. Accuracy of information in the publications was examined by comparison to the information in the EPARs. Only 55% of the trials with insomnia medications identified in EPARs were published. Positive trials were approximately two times more likely to be published. The lag time from study completion to publication was shorter for the positive compared to the negative trials. Sample size did not correlate with publication of negative trials. The meta-analysis of the effect size of insomnia medication was 1.6 times larger in the published data compared to the complete data. While the primary end points of the trials were reported reliably in the publications, remarkable inconsistencies were detected in the reporting of the secondary end points, methods, results and, especially safety. In conclusion, selective publication and reporting lead to an overestimation of efficacy and underestimation of safety of insomnia products. Authors of treatment guidelines should be aware of this bias. EPARs/FDA reviews provide a more unbiased view of the benefit-risk balance of insomnia and other medications and hence these documents should be consulted by e.g. authors of meta-analyses and of treatment guidelines.

Psychopharmacology for children: From off label use to registration

Pharmacological treatment of children and adolescents is largely based on evidence from adults studies. There is, however, growing awareness that this evidence cannot simply be extrapolated to children. The Dutch Medicines Evaluation Board (MEB) in collaboration with the Child and Adolescent section of the Dutch Association of Psychiatry and the National Expertise Centre Child and Adolescent Psychiatry have organised a workshop to discuss the kind of evidence that would be necessary and the methods involved. There was consensus about the need to demonstrate efficacy in targeted disorders as well as symptoms within specific disorders and about the need for separate evidence for children and for adolescents. In addition, too little is known about safety, especially long-term safety, as consequences of treatment. Main issues are effects on growth, cognitive, motor, emotional, and sexual development, metabolic symptoms, cardiotoxicity, and dependence. Specific methodological issues were discussed, such as the role of different informants and the high rate of comorbidity.