Personalised treatment for Alcohol Use Disorder: Identification and intervention of target mechanisms

Abstract

Alcohol is among the leading contributors to the global burden of morbidity and mortality. Alcohol Use Disorders (AUD) account for the majority of this burden. Numerous interventions have demonstrated effectiveness in the treatment of AUD, but treatment response is modest and relapse rates remain high. No one treatment approach has demonstrated unequivocal superiority, prompting calls for individualised intervention strategies. Insufficient understanding of the mechanisms involved in AUD maintenance and treatment response impair the design and implementation of such approaches. The aim of this thesis was to progress understanding of potential treatment targets within personalised treatments for AUD. Alcohol craving, alcohol outcome expectancies, and rash impulsivity comprise the focus of this thesis, as each has been implicated in AUD maintenance and treatment response. A series of studies examining clinical applications of alcohol craving, outcome expectancies, and rash impulsivity within personalised AUD interventions were conducted.Study 1 (Chapter Two) examined the clinical utility of alcohol craving, focusing on issues of measurement. Highlighting the absence of a theoretically and psychometrically robust measure of craving which is also brief enough to be routinely administered within busy clinical settings, the study aimed to develop a new measure. Using data from 747 treatment seeking AUD patients the 22-item Alcohol Craving Experience Questionnaire (ACE) was reduced to 5-items while preserving its key theoretical elements, psychometric integrity, and clinical implications. The shortened ‘Mini ACE’ (MACE) is ideal for use with AUD populations in time-limited settings, such as weekly assessment in treatment contexts. An extended review of common issues in craving measurement is provided in the following chapter (Chapter Three). The chapter is intended to assist researchers and treatment providers in the selection, effective application, interpretation of the scales comprising the Alcohol Craving Experience Questionnaire.Study 2 (Chapter Four) highlights an absence of research on targeting alcohol outcome expectancies within Cognitive Behavioural Therapy (CBT) for AUD. Alcohol expectancies of 175 patients who completed a 12-week CBT program for AUD were assessed pre-and post-treatment. Several positive expectancies were predictive of drinking behaviour during treatment, and most reduced toward community norms post-treatment. However, positive expectancy change was not related to drinking behaviour during treatment, challenging cognitive theory emphasising the importance of this process. Increase in negative expectations of alcohols effect on mood was associated with fewer drinking days, supporting emphasis on modification of negative alcohol expectations within treatment. Further implications of both positive and negative alcohol outcome expectancies regarding AUD treatment are discussed.Study 3 (Chapter Five) is a large clinical randomised controlled trial (RCT; n = 379) examining the effectiveness of personalising AUD treatment based on individual differences in a) alcohol craving, b) alcohol outcome expectancies, and c) rash impulsivity. Patients were randomly assigned to Treatment as Usual (TAU, 8 sessions of standard CBT for AUD) or Targeted Treatment (TT). TT manualised content for 4 of 8-sessions sessions to address the risk-factor most elevated for each patient based on measures standardised by AUD norms (either Craving, Expectancy or Impulsivity). No significant differences in treatment outcome were observed between overall TT and standard, CBT (TAU) conditions. Craving and impulsivity, though not positive outcome expectancies, were found to reduce more for patients within their respective target modules. Only reduction in craving was associated with reduced drinking, supporting an indirect effect for personalised interventions targeting craving. The effectiveness of targeting rash impulsivity and outcome expectancies within personalised AUD could not be confirmed. Alcohol craving stands out as useful construct for consideration within future research of personalised interventions.Study 4 (Chapter Six) examined the association between alcohol craving and rash impulsivity in the prediction of treatment response. Craving and rash impulsivity were positively associated among 470 AUD patients. Both were found to predict lapse-risk during treatment, though impulsivity was mediated by craving. Patients with higher craving pre-treatment, were found to have more persistent craving as treatment progressed, which increased risk of lapse. These findings have clinical implications for the assessment and treatment of AUD, as well as theoretical implications for cognitive models of craving and impulsivity. The mediating role of craving is further considered in the context of the RCT findings (Chapter Three, Study 4).These four studies progress understanding of key mechanisms implicated within AUD maintenance and treatment response. Support was found for the utility of alcohol craving, outcome expectancies, and rash impulsivity as prognostic markers for AUD treatment. The novel contributions of this thesis pertain to understanding their utility as treatment targets. The processes which determine treatment response are complex, requiring equally sophisticated procedures to effectively adapt treatment to individuals. The findings of this program of research can inform the progression of such approaches.