The role of impulsivity in relapse vulnerability
Highlights
► This paper reviews evidence for an important role of impulsivity in drug addiction with a particular focus on relapse vulnerability. ► Impulsivity levels can reliably predict onset and maintenance of drug taking and seeking as well as relapse rates. ► Impulsivity as a target for pharmacological intervention to prevent relapse may seem a promising strategy. ► It remains to be determined whether impulse control and relapse vulnerability are interrelated processes or represent independent entities.
Introduction
In searching for novel therapeutic interventions to facilitate and promote recovery in drug dependence, the contribution of executive cognitive disturbances as risk factors has received considerable attention over the last decade. In particular, diminished cognitive control and impulsivity have been linked to the onset, maintenance and relapsing nature of drug dependence. Indeed, maladaptive impulsivity is a common behavioral phenomenon in various populations of drug-dependent subjects, including stimulant and nonstimulant users [1, 2, 3]. The idea that impulsivity might be a vulnerability trait for drug abuse and dependence [4] has received support from several prospective studies in humans [5•, 6•, 7•] and preclinical studies in laboratory animals (see preclinical observations).
As has been extensively and elegantly reviewed elsewhere [8••, 9, 10, 11], there is considerable evidence for the idea that impulsivity is a multifactorial construct consisting of neuroanatomically and neurobiologically separable behavioral phenomena. In order to operationalize these forms of impulsive behavior in humans often self-report measures such as the Barratt Impulsiveness Scale are employed, as well as laboratory measures from neuropsychological tasks including the stop-signal task and delay discounting tasks. In addition, in laboratory animals various translational analogues have been developed based on the aforementioned human neuropsychological tasks. By and large, one can recognize impulsive behavior that results from diminished inhibitory response control processes, which is often referred to as impulsive action. These impulsive behaviors, although there is neuroanatomical and neurobiological overlap, largely differ from those originating from delay discounting and impulsive decision-making processes often termed impulsive choice. It is of interest that the dissociation between impulsive action and impulsive choice assessed in laboratory tasks appears to be a cross-species phenomenon as it has recently been demonstrated in healthy volunteers and laboratory rats using a translational approach [12].
Importantly, regarding the collective work over the last decade the varieties of impulsivity seem relevant for predicting several aspects of reward sensitivity and relapse vulnerability. Much of the evidence for this idea is derived from preclinical animal models of impulsive behavior and drug self-administration, as combining these models within individuals allow the investigation of causal interrelationships between levels of impulsivity and various aspects of sensitivity towards the addictive properties of drugs of abuse including relapse vulnerability. The purpose of this paper is to briefly summarize the current findings in particular with respect to the role of impulsivity in relapse vulnerability in drug dependence and to address the implications of these findings for rehabilitation.
Section snippets
Clinical observations
Of relevance to the hypothesis that impulsivity is an important behavioral trait that facilitates and sustains drug consumption and drug seeking are several clinical observations of the past decade. These studies have demonstrated that disturbances in cognitive functioning, comprising risk-taking and decision-making, and associated abnormal frontostriatal brain activation patterns are strong determinants of treatment outcome and relapse vulnerability in alcoholics [13•] and
Preclinical observations
Relapse to drug use after a period of withdrawal is a hallmark of drug addiction. In this regard, self-administration-reinstatement models are the best-validated animal models in addiction research to study the neurobiology of relapse and to test (pharmacological) interventions as possible relapse prevention strategies [27]. In addition, these models appear to be powerful tools in detecting individual differences in vulnerability to addictive behaviors by creating the possibility to separate
Treatment options: preclinical observations
From a clinical and therapeutic perspective the critical question arises as to whether improving impulse control by pharmacological tools could promote and support abstinence and reduce the risk to relapse in drug-dependent individuals. In this respect, previous preclinical studies have demonstrated beneficial effects of the clinically employed norepinephrine transporter inhibitor atomoxetine on impulsivity [42, 43] and drug taking or seeking [44•], supporting this notion. Nonetheless, it
Treatment options: clinical observations
There is preliminary empirical evidence from clinical studies indicating effects of attention-deficit/hyperactivity disorder (ADHD) approved drugs to ameliorate heightened impulsivity on drug seeking and taking. Nonetheless, the picture that emerges from these different lines of evidence is rather inconsistent and inconclusive. To date, the majority of these studies has been conducted in ADHD patients with comorbid drug dependence. Although there is high comorbidity between these disorders [50]
Conclusions
Both preclinical animal studies and human clinical studies report a very tight relationship between impulsivity and various measures of addictive behavior. Impulsivity levels can reliably predict onset and maintenance of drug taking and seeking as well as relapse rates. Impulsivity as a target for pharmacological interventions to prevent relapse may, therefore, appear a promising treatment strategy, but the preliminary clinical observations so far have been somewhat disappointing. It needs to
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
References (64)
- et al.
Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies
Neurosci Biobehav Rev
(2008) - et al.
Poor response inhibition as a predictor of problem drinking and illicit drug use in adolescents at risk for alcoholism and other substance use disorders
J Am Acad Child Adolesc Psychiatry
(2006) - et al.
Does delay discounting play an etiological role in smoking or is it a consequence of smoking?
Drug Alcohol Depend
(2009) Varieties of impulsivity
Psychopharmacology (Berl)
(1999)- et al.
The relationship between impulsive choice and impulsive action: a cross-species translational study
PLoS ONE
(2012) - et al.
Delayed reward discounting predicts treatment response for heavy drinkers receiving smoking cessation treatment
Drug Alcohol Depend
(2009) - et al.
Delay discounting predicts postpartum relapse to cigarette smoking among pregnant women
Exp Clin Psychopharmacol
(2007) - et al.
Delay discounting predicts adolescent substance abuse treatment outcome
Exp Clin Psychopharmacol
(2012) - et al.
Neuropsychological predictors of clinical outcome in opiate addiction
Drug Alcohol Depend
(2008) - et al.
Reinstatement — toward a model of relapse
Psychopharmacology (Berl)
(2003)