When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

BACKGROUND: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. METHODS: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. OUTCOMES: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. INTERPRETATION: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial.

Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients.

A multi-centre, randomised, double-blind, placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study).

Based on many clinical and preclinical findings the 'vigilance regulation model of mania' postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study - a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) - assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20-40mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20-40mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. TRIAL REGISTRATION: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).

Discriminant validity of the ZKPQ in a sample meeting BPD diagnosis vs. normal-range controls.

Widiger and Simonsen (2005) state that given the limitations of the categorical model of Personality Disorders classification proposals are to be expected for dimensional classifications. The purpose of this paper is to test the alternative five factorial model (AFFM) of personality in a sample with PDs. Subjects were administered the ZKPQ to test the discriminant capacity of the AFFM in classifying subjects diagnosed with BPD (n = 74) vs normal-range controls (n = 148) paired by age and sex, and identifying sensitive and/or specific dimensions that can be of help in diagnosing BPD. The results showed that high scores on N-Anx and Imp-SS, and low scores on Act are prognostic factors for being diagnosed with BPD. Likewise, this model correctly classified 88% of subjects with a kappa index of 0.73. The AFFM of personality appears to have a substantial power for predicting SCID-II interview-based BPD diagnosis.

The 'European Alliance Against Depression (EAAD)': a multifaceted, community-based action programme against depression and suicidality.

Action programmes fostering partnerships and bringing together regional and national authorities to promote the care of depressed patients are urgently needed. In 2001 the 'Nuremberg Alliance Against Depression' was initiated as a community-based model project within the large-scale 'German Research Network on Depression and Suicidality' (Kompetenznetz 'Depression, Suizidalität'). The 'Nuremberg Alliance Against Depression' was an action programme, conducted in the city of Nuremberg (500,000 inhabitants) in 2001/2002, addressing four intervention levels (Hegerl et al. Psychol Med 2006;36:1225). Based on the positive results of the Nuremberg project (a significant reduction of suicidal behaviour by more than 20%) 18 international partners representing 16 different European countries established the 'European Alliance Against Depression' (EAAD) in 2004. Based on the four-level approach of the Nuremberg project, all regional partners initiated respective regional intervention programmes addressing depression and suicidality. Evaluation of the activities takes place on regional and international levels. This paper gives a brief overview of the background for and experiences with the EAAD. It describes the components of the programme, provides the rationale for the intervention and outlines the current status of the project. The aim of the paper is to disseminate information about the programme's potential to reduce suicidal behaviour and to provide examples of how European community-based 'best practice' models for improving the care of depressed patients and suicidal persons can be implemented using a bottom-up approach. EAAD is mentioned by the European commission as a best practice example within the Green Paper 'Improving the mental health of the population: Towards a strategy on mental health for the European Union' (European Commission 2005).