Prazosin Effects on Stress‐ and Cue‐Induced Craving and Stress Response in Alcohol‐Dependent Individuals: Preliminary Findings

Abstract

Background Stress, alcohol cues and dysregulated stress responses increase alcohol craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress and cue-induced alcohol craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha1 receptor antagonist, prazosin, in modulating these relapse-relevant factors in alcohol dependent (AD) individuals. Methods Seventeen early abstinent, treatment-seeking alcohol dependent individuals (12 Males /5 Females) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double-blind, placebo controlled manner over four weeks. During week 4, all patients participated in a 3-day laboratory experiment involving 5-min guided imagery exposure to stress, alcohol cue and neutral-relaxing/control conditions, one exposure per day, on consecutive days in a random, counterbalanced order. Alcohol craving, anxiety and negative emotion, cardiovascular measures, plasma hypothalamic-pituitary-adrenal (HPA; cortisol, ACTH) were assessed repeatedly in each session. Results The prazosin group (n=9) versus the placebo group (n=8) showed significantly lower alcohol craving, anxiety and negative emotion following stress exposure. The placebo group also showed significantly increased stress and cue-induced alcohol craving, anxiety, negative emotion and blood pressure as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in craving, anxiety, negative emotion and blood pressure, and no blunted HPA response to stress and alcohol cue exposure. Conclusions Prazosin appears efficacious in decreasing stress- and cue-induced alcohol craving and may normalize the stress dysregulation associated with early recovery from alcoholism. Further research to assess the efficacy of prazosin in reducing alcohol craving and stress-related relapse risk is warranted.

The Corticotropin Releasing Hormone-1 (CRH1) Receptor Antagonist Pexacerfont in Alcohol Dependence: A Randomized Controlled Experimental Medicine Study

“…Our study obtained craving-and distress-responses of a magnitude very similar to that reported in non-selected alcohol-dependent patients (see eg, Sinha et al, 2011), and shown to be sensitive to pharmacological effects (Fox et al, 2012). We did not directly evaluate the clinical efficacy of pexacerfont in alcoholism, and limited data are available to determine the predictive validity of the surrogate markers we obtained.…”

Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations

“…Prazosin treatment also facilitates abstinence in treatment-seeking alcohol-dependent men, as demonstrated in a study in which the subjects were unaware of their treatment condition (prazosin vs placebo) and there were no differences in side effects reported (Simpson et al, 2009). In addition, prazosin decreases stress-and cue-induced alcohol craving in alcohol-dependent men and women (Fox et al, 2012). The present study investigated whether prazosin, administered only at the time of stress during alcohol deprivation, would block increases in anxiety behavior after alcohol reinstatement and an additional deprivation.…”

Relationship Between Drug Dreams, Affect, and Craving During Treatment for Substance Dependence

“…Also, drugs such as Prazosin, an alpha-1 adrenergic antagonist, might be considered as adjunct pharmacotherapy for individuals who are particularly troubled by DD. This drug is considered an effective treatment for posttraumatic stress disorder nightmares (Kung et al, 2012), and there is preliminary evidence that it can reduce craving precipitated by stress and exposure to drug cues (Fox et al, 2012). Incidentally, if DDs are partly reflective of craving and negative affect experienced during the day as a result of withdrawal, then clinical approaches to reduce their impact could be conceived as a broader withdrawal management strategy.…”