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Psychopharmacological Options for Treating Impulsivity: Page 2 of 5

Psychopharmacological Options for Treating Impulsivity: Page 2 of 5

Pharmacological class, behaviors for which they are effective for impulsivityTable: Pharmacological class and the behaviors for which they are effe...

Impulsivity is a tendency to engage in behaviors that are premature, risky, and/or poorly thought-out, resulting in unwanted or negative outcomes. Clinical and neuroscience research has demonstrated that impulsivity cuts across many psychiatric disorders and therefore may represent a useful target for treatment. Consistent with this interest in impulsivity, the NIMH strategic plan is focusing on new ways of classifying psychopathology based on dimensions of behavior and neurobiology (research domain criteria), such as impulsivity, instead of traditional DSM disorders. Although the pharmacological treatment of impulsivity represents an exciting and possibly more effective means of relieving the burden of mental health illness, precisely what is meant by impulsivity and its neurobiological substrates remains a topic of ongoing investigation and clarification.

Impulsivity is a multidimensional construct that may involve disruption within a wide range of neuropsychological processes, including aspects of attention, decision making, reward discounting, perception, and coordination of motor or cognitive responses. From a neurobiological perspective, it is argued that impulsivity derives from dysfunction within corticostriatal neurocircuitry, with excess engagement from the striatum (nucleus accumbens, putamen/caudate) driving the impulsive behaviors, coupled with a lack of top-down control from the cortices (anterior cingulate, orbitofrontal, and inferior frontal regions).1,2

Another means of conceptualizing impulsivity is from the perspective of psychiatric disorders, ie, top-level symptoms. Although a few disorders have historically been categorized as impulse control disorders (eg, gambling disorder, kleptomania), many others are defined by their core element of impulsive behaviors (eg, substance use disorders, ADHD, and certain personality disorders). Many of the pharmacological options that reduce impulsive behaviors in one disorder may be useful for the impulsivity seen in another disorder.

For the purposes of this review, we focus on several classes of pharmacological agents and discuss the extent to which they are effective in reducing impulsivity (Table). Of course, there are multiple forms of impulsivity (eg, from a cognitive perspective, “impulsive action,” ie, inability to inhibit motor responses, and “impulsive choice,” ie, preference for immediate smaller rewards to the detriment of long-term outcomes, are two commonly seen forms of impulsivity), and different forms of impulsivity can co-occur within the same person. For example, on cognitive assessments, someone with a drug use disorder may exhibit problems with impulsive action and impulsive choice. In a few cases, there are data regarding which type of impulsivity the pharmacological agent is targeting. In those cases, we discuss the subtype of impulsivity in more detail.

Selective serotonin reuptake inhibitors

SSRIs are some of the most frequently prescribed psychiatric medications. Basic research has long shown that low levels of the serotonin metabolite 5-hydroxyindoleacetic acid and blunted serotonergic response within the ventromedial prefrontal cortex are associated with impulsive behaviors, especially aggression. Imaging studies using meta-chlorophenylpiperazine, a nonspecific serotonin agonist, show activation of the anterior cingulate in controls but not in impulsive aggressive individuals.3 Neuroscience research also suggests that serotonergic activity within the medial prefrontal cortex and the orbitofrontal cortex plays a role in discounting behavior, a form of impulsive choice.4 Moreover, serotonergic manipulations can enhance response inhibition (ie, impulsive action), at least in Parkinson disease (presumably this disorder is characterized in part by a serotonergic deficit).5 Most studies in translational models and in healthy volunteers suggest, however, that serotonin manipulations do not significantly affect response inhibition but that other classes of agents (especially stimulants) do.

One might expect that SSRIs are the treatment of choice for at least some forms of impulsivity. The human data in impulsive disorders, however, have not fully borne out that hypothesis (see, for example, Bartley and Bloch6 and Rothbart et al7). One area in which SSRIs appear to be beneficial is in the treatment of impulsive aggression. A large, double-blind, placebo-controlled trial involving 100 individuals with intermittent explosive disorder found that fluoxetine resulted in a sustained reduction in aggression and irritability as early as the second week of treatment. Full or partial remission of impulsive aggressive behaviors occurred in 46% of fluoxetine-treated patients.8

Results of SSRI treatment of other impulsive behaviors, however, have been mixed at best. In studies of patients with gambling disorder, substance use disorders, kleptomania, trichotillomania, and compulsive buying, SSRIs have failed to produce any consistent beneficial effects compared with placebo. In our experience, these medications afford partial benefit for those individuals who report their impulsive behavior is worsened by depression or anxiety. It is not uncommon for individuals to use impulsive behaviors as a distraction from or a means to cope with depression or anxiety. In such instances, the person may report some benefit but the core impulsive behavior seems less likely to be directly affected by these agents.

SSRIs are not without their potential problems in impulsive behaviors. Take the case of William H who reported impulsive sexual behavior.

CASE VIGNETTE

William H spent hours every day looking at pornography on the Internet and paid prostitutes for sexual favors. He was treated with fluvoxamine titrated to 200 mg daily. He reported that the sexual adverse effects (ie, loss of libido, delayed orgasm) resulted in his need to increase, rather than reduce, the riskiness of his sexual behavior in order to override these effects. He began having casual sex without condoms and contracted HIV as a result. In his case, the SSRI may have contributed to the worsening of the impulsive behavior.

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