Medications development to treat alcohol dependence: a vision for the next decade

Abstract

More than 76 million people worldwide are estimated to have diagnosable Alcohol Use Disorders (AUDs) (alcohol abuse or dependence), making these disorders a major global health problem. Pharmacotherapy offers promising means for treating AUDs, and significant progress has been made in the past 20 years. The U.S. Food and Drug Administration approved three of the four medications for alcoholism in the last two decades. Unfortunately, these medications do not work for everyone, prompting the need for a personalized approach to optimize clinical benefit or more efficacious medications that can treat a wider range of patients, or both. To promote global health, the potential reorganization of the National Institutes of Health (NIH) must continue to support the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA’s) vision of ensuring the development and delivery of new and more efficacious medications to treat AUDs in the coming decade. To achieve this objective, the NIAAA Medications Development Team has identified three fundamental long-range goals: 1) to make the drug development process more efficient; 2) to identify more efficacious medications, personalize treatment approaches, or both, and 3) to facilitate the implementation and adaptation of medications in real-world treatment settings. These goals will be carried out through seven key objectives. This paper describes those objectives in terms of rationale and strategy. Successful implementation of these objectives will result in the development of more efficacious and safe medications, provide a greater selection of therapy options, and ultimately lessen the impact of this devastating disorder.

The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects

“…Model-specific covariates are noted in the relevant figure legends. The Kenward-Roger correction (Kenward and Roger, 1997) was used in all models, as the use of this correction is highly recommended in repeated-measures models with more complex covariance structures, especially when there is an unbalanced design (Littell et al, 2006). We note that this correction may result in atypical denominator degrees of freedom compared with traditional repeated-measures models (e.g., denominator degrees of freedom may actually be higher than the number of subjects).…”

“…A major objective of alcohol research is therefore to develop medications with an ability to prevent relapse to alcohol use. Preclinical studies have identified several classes of molecules with an ability to block relapse-like behaviors in experimental animals Litten et al, 2012). One of the conclusions that have emerged from this research is that type 1 receptors for corticotropin-releasing factor 1 (CRF1) are key mediators of stress-induced alcohol seeking.…”

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

“…However, existing pharmacotherapy has shown limited efficacy (Anton et al 2006); therefore, further investigation of possible alcohol neurochemical targets could lead to new pharmacological interventions (Heilig & Egli 2006;Litten et al 2012). Alcohol targets components of the mesolimbic dopamine system (Larsson & Engel 2004;Vengeliene et al 2008;Soderpalm, Lof, & Ericson 2009), which is involved in the expression of its reinforcing properties (Adinoff 2004).…”

Acamprosate Produces Its Anti-Relapse Effects Via Calcium

“…One further consequence of excessive alcohol use is that 76 million adults worldwide are alcohol dependent (Rehm et al, 2009). Currently, there are four medications approved by the U.S. Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, oral naltrexone, a longlasting injectable naltrexone, and acamprosate (Litten et al, 2012). In Europe, nalmefene has been also approved in 2013 (Mann et al, 2013).…”