Effectiveness of adjuvant occupational therapy in employees with depression: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder is among the medical conditions with the highest negative impact on work outcome. However, little is known regarding evidence-based interventions targeting the improvement of work outcomes in depressed employees. In this paper, the design of a randomized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression. This occupational intervention is based on an earlier intervention, which was designed and proven effective by our research group, and is the only intervention to date that specifically targets work outcome in depressed employees.</p> <p>Methods/Design</p> <p>In a two-arm randomized controlled trial, a total of 117 participants are randomized to either 'care as usual' or <it>' </it>care as usual' with the addition of occupational therapy. Patients included in the study are employees who are absent from work due to depression for at least 25% of their contract hours, and who have a possibility of returning to their own or a new job. The occupational intervention consists of six individual sessions, eight group sessions and a work-place visit over a 16-week period. By increasing exposure to the working environment, and by stimulating communication between employer and employee, the occupational intervention aims to enhance self-efficacy and the acquisition of more adaptive coping strategies. Assessments take place at baseline, and at 6, 12, and 18-month follow-ups. Primary outcome measure is work participation (hours of absenteeism and time until work resumption). Secondary outcome measures are work functioning, symptomatology, health-related quality of life, and neurocognitive functioning. In addition, cost-effectiveness is evaluated from a societal perspective. Finally, mechanisms of change (intermediate outcomes) and potential patient-treatment matching variables are investigated.</p> <p>Discussion</p> <p>This study hopes to provide valuable knowledge regarding an intervention to treat depression, one of the most common and debilitating diseases of our time. If our intervention is proven (cost-) effective, the personal, economic, and health benefits for both patients and employers are far-reaching.</p> <p>Trial registration number</p> <p>NTR2057</p

Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder

BACKGROUND: In major depressive disorder, selective serotonin reuptake inhibitors target the serotonin transporter (SERT). Their response rates (30-50%) are modified by SERT promotor polymorphisms (5-HTTLPR). OBJECTIVES: To quantify the relationship between SERT occupancy and response, and whether 5-HTTLPR is a modifier. METHODS: Drug-free depressed outpatients (n=49; both sexes; aged 25-55 years), received paroxetine (20 mg/day). We quantified SERT occupancy with iodine-123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane single-photon emission computed tomography imaging at baseline and after 6 weeks; we genotyped 5-HTTLPR (S, LG, LA). Primary outcomes: percentage decrease in 17-item Hamilton Depression Rating Scale and response (>/=50% decrease of 17-item Hamilton Depression Rating Scale). RESULTS: A significant positive relationship between SERT occupancy and clinical response existed only in the LA/LA genotype (P <0.002). Relative to paroxetine serum concentrations maximal midbrain SERT occupancy was numerically higher for LA/LA compared with other genotypes, but this difference was nonsignificant (P=0.188). CONCLUSION: Higher SERT occupancy is only associated with more clinical improvement in the LA/LA genotype. We hypothesize that the LA/LA carriers have a more dynamic serotonergic system, which seems more responsive to selective serotonin reuptake inhibitors. (ISRCTN trial register ISRCTN44111488; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=193

Patient-treatment matching with anti-craving medications in alcohol-dependent patients: A review on phenotypic, endophenotypic and genetic indicators.

International audienceObjectives: Craving plays an important role in the development and maintenance of alcohol dependence and in relapse after periods of abstinence. Anti-craving compounds, such as acamprosate, naltrexone or serotonergic compounds, are found to be only moderately effective. These moderate effects might be due to inadequate matching of specific patients to specific treatments. In 1999, Verheul et al. proposed a three-pathway model of craving in alcoholics, which hypothesised that reward drinkers would better respond to naltrexone, relief drinkers to acamprosate and obsessive drinkers to serotonergic compounds. However, these matching hypotheses are not yet validated. This article reviews the literature on predictors and matching variables of the effectiveness of pharmacological interventions in alcohol dependent patients directed at the reduction of craving and the prevention of relapse. Methods: Studies were selected through a literature search in September 2004, focusing on matching or predicting variables for anti-craving compounds in the treatment of alcoholics. Matching or predicting variables were categorised as either phenotypic (e.g., level of baseline anxiety), endophenotypic (e.g., physiological cue reactivity) or genetic (e.g., m opioid receptor polymorphisms). Results: Studies using clinical or phenotypic effect modifiers have produced inconsistent and rather disappointing results. In contrast, the predictive value of genetic effect modifiers are quite promising (e.g., m opioid receptor polymorphisms). No studies that looked at endophenotypic predicting or matching variables were identified. Conclusion: It is concluded that phenotypic matching variables might be too distal, i.e., far removed from the pathogenic process, and that matching research should shift its attention toward more proximal variables (e.g., genetic and endophenotypic variables)

Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators

Acamprosate and naltrexone are effective medications in the treatment of alcoholism. However. effect sizes are modest. Pharmacogenomics may improve patient-treatment-matching and effect sizes. It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system, whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system. Alcohol-dependent subjects were randomly assigned to either acamprosate or naltrexone. Subjects participated in a cue-exposure experiment at the day before and at the last day of medication. Reductions in cue-induced craving and physiological cue reactivity were measured. Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid, dopamine, glutamate and GABA-receptors. Significant matching effects were found for polymorphisms at the DRD2. GABRA6 and GABRB2 gene. In addition, a trend was found for the OPRM1 polymorphism. This provides evidence for the matching potential of genotypes. It is expected that more effective treatments can be offered when genetic information is used in patient-treatment-matchin