Patients' Perspectives on the Development of Prescription Opioid Use Disorder in Patients with Chronic Non-Cancer Pain

INTRODUCTION: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients' perspective on developing a prescription OUD. METHODS: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. RESULTS: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. CONCLUSION: Patients' experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use

The Relationship of Early Sleep Improvement With Response to Pharmacotherapy in Unipolar Psychotic Depression

BACKGROUND: Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific. METHODS: This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks). RESULTS: EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = &lt;0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome. CONCLUSIONS: Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.</p

A genetic risk score to predict treatment nonresponse in psychotic depression

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = −0.32, p = 0.0023, n = 88) and remission (r = −0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.</p

Exploring Brain Derived Neurotrophic Factor and Cell Adhesion Molecules as Biomarkers for the Transdiagnostic Symptom Anhedonia in Alcohol Use Disorder and Comorbid Depression

Background: Alcohol Use Disorder (AUD) and depressive disorder often co-exist and have a shared heritability. This study aimed to investigate Brain-Derived Neurotrophic Factor (BDNF) and three Cell Adhesion Molecules (CAMs) as transdiagnostic biomarkers in AUD and depression co-morbidity. Methods: In a cross-sectional study, patients with AUD (n=22), AUD and depression (n=19), and healthy controls (n=20) were examined. Depression and anxiety severity were assessed using the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale. Anhedonia, alcohol use and dependence, craving, and social adaptation were assessed through self-report questionnaires. BDNF and CAM concentrations in peripheral serum were measured after overnight fasting using a Luminex assay. After controlling for age and gender, biomarker levels were compared across groups. The association between biomarker concentrations and symptom severity scales were explored using correlation and multiple regression analyses. Results: BDNF and Neuronal CAM were lower in patients with AUD with and without depression compared to healthy controls. No differences were observed for Vascular CAM-1 and Interstitial CAM-1. BDNF correlated negatively with anhedonia levels. BDNF, age and gender together explained 21% of variability in anhedonia levels. Conclusion: This pilot study suggests that peripheral levels of BDNF and NCAM might be reduced in AUD with and without comorbid mood disorder. Since low BDNF levels were associated with self- reported anhedonia across these conditions, BDNF and anhedonia might reflect transdiagnostic aspects involved in AUD and depression

A genetic risk score to predict treatment nonresponse in psychotic depression

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = −0.32, p = 0.0023, n = 88) and remission (r = −0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.</p

Effect of apomorphine on cognitive performance and sensorimotor gating in humans

Contains fulltext : 88792.pdf (publisher's version ) (Closed access)INTRODUCTION: Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. METHODS: Fifteen healthy male volunteers received apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. RESULTS: After administration of apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain apomorphine levels after subcutaneous administration. CONCLUSION: The apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of apomorphine.1 januari 201

The World Federation of ADHD International Consensus Statement:208 Evidence-based conclusions about the disorder

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.</p

Using the Recovery Capital Model to Explore Barriers to and Facilitators of Recovery in Individuals with Substance Use Disorder, Psychiatric Comorbidity and Mild-to-Borderline Intellectual Disability: A Case Series

Recovery capital (RC) encompasses the wide range of resources individuals can employ to recover from Substance Use Disorder (SUD). It consists of five subdomains: human, social, cultural, financial, and community RC. Negative recovery capital (NRC) represents the obstacles to recovery. Research on (N)RC in complex multimorbid populations is scarce. This study offers an initial exploration of the viability of (N)RC in three individuals with SUD, psychiatric comorbidities, and an intellectual disability (a triple diagnosis) in inpatient addiction treatment. We collected case file data, ranked recovery goals, and conducted follow-up interviews. The data were subjected to template analysis, using (N)RC domains as codes. All domains were prevalent and relevant, showing dynamic and reciprocal effects, influenced by critical life events acting as catalysts. Notably, during treatment, patients prioritized individual skill development despite challenges in other domains. RC emerges as a valuable concept for mapping recovery barriers and facilitators in individuals with a triple diagnosis, serving as an alternative to the medical model and complementing the biopsychosocial model. It provides a systematic framework to assess critical factors for recovery in complex cases and accordingly align interventions. Future studies should explore the intersections of NRC domains and the dynamic nature of (N)RC to enhance the understanding of the challenges faced by individuals with a triple diagnosis