Emerging drugs in phase II and III clinical development for the treatment of alcohol use disorder.

INTRODUCTION: Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their communities and society at large. Even though pharmacotherapy is an integral part of AUD treatment, the few available substances show limited efficacy and limited clinical impact. Thus, there is a need for new innovative pharmacotherapeutic approaches. AREAS COVERED: This paper provides a comprehensive review of drugs approved for the treatment of AUD as well as those currently in phase II and III development. Data from recent clinical trials has been reviewed and supplemented by additional literature based on a systematic search of the PubMed database and clinical trials registries. Compounds discussed include disulfiram, naltrexone, nalmefene, acamprosat, baclofen, sodium oxybate, doxazosin, varenicline, zonisamide, gabapentin, apremilast, ibudilast, ivermectin, tolcapone, mifepristone, suvorexant, ketamine, psilocybin, semaglutide, oxytocin and cannabidiol. EXPERT OPINION: Even though the majority of the discussed compounds lack sufficient evidence to support their efficacy, multiple promising new treatment options are currently under investigation. Future research has to consider specific phenotypes and subgroups of AUD as well as a possible enhancement of the effects of psychotherapy through combination with pharmacotherapy. Practitioners should be encouraged to use available compounds to support existing therapeutic regimens.

Stability of resilience in times of the COVID-19 pandemic.

There is disagreement among researchers regarding the conceptualization of resilience as a dynamic state or stable trait. Aiming to shed light on the state-versus-trait debate, we explored the stability and construct validity of four of the most frequently utilized state or trait resilience scales in a longitudinal assessment. Additionally, we examined the predictive validity of these scales. Our study was conducted before and during the COVID-19 pandemic, which served as collectively experienced adversity. Correlations among the resilience scales and among resilience scales and Big Five personality traits were strong. All except one scale showed high test-retest correlations. Experience of an additional critical life event during the pandemic led to an increase in resilience. Other than in cross-sectional studies, associations between resilience and psychological distress were weak, because personality and baseline psychological distress were controlled for. Nevertheless, next to personality, resilience explained additional variance in distress change. Our results show relatively high stability of resilience overall. Yet, they also confirm dynamic resilience features, suggesting that resilience change occurs with significant adversity, leading to improved adaptation. To gauge the true association between resilience and mental health, baseline levels of these variables as well as personality traits should be considered.

Resilience and personality as predictors of the biological stress load during the first wave of the Covid-19 pandemic in Germany.

Since the Covid-19 outbreak, pandemic-specific stressors have potentiated the-already severe-stress load across the world. However, stress is more than an adverse state, and chronic exposure is causally involved in the development of mental and physical disease. We ask the question whether resilience and the Big Five personality traits predict the biological stress response to the first lockdown in Germany. In a prospective, longitudinal, observational study, N = 80 adult volunteers completed an internet-based survey prior to the first Covid-19-related fatality in Germany (T0), during the first lockdown period (T1), and during the subsequent period of contact restrictions (T2). Hair strands for the assessment of systemic cortisol and cortisone levels were collected at T2. Higher neuroticism predicted higher hair cortisol, cortisone and subjective stress levels. Higher extraversion predicted higher hair cortisone levels. Resilience showed no effects on subjective or physiological stress markers. Our study provides longitudinal evidence that neuroticism and extraversion have predictive utility for the accumulation of biological stress over the course of the pandemic. While in pre-pandemic times individuals high in neuroticism are typically at risk for worse health outcomes, extraverted individuals tend to be protected. We conclude that, in the pandemic context, we cannot simply generalize from pre-pandemic knowledge. Neurotic individuals may currently suffer due to their general emotional lability. Extraverted individuals may primarily be socially stressed. Individualized stress management programs need to be developed, and offered in a lockdown-friendly format, to minimize the stress burden caused by Covid-19 or future pandemics and to protect the most severely affected individuals from the development of stress-associated disease.