Although SSRIs may reduce some impulsive behaviors, it is unclear what the mechanism of action is. A recent study of impulsivity in patients with Parkinson disease found that the SSRI citalopram reduced impulsivity on 2 tasks of impulsive action (ie, the stop-signal and go/no-go tasks) but did not produce any detectable improvements in core symptoms of the disorder.5 Similarly, a study of 38 adults with gambling disorders treated with either paroxetine or placebo found that paroxetine reduced impulsivity, measured with the Eysenck Impulsiveness Questionnaire, but there were no differences in gambling behavior between paroxetine and placebo.9 It appears that some objective cognitive measures of impulsivity respond better to SSRIs than the actual impulsive behavior.
Selective noradrenergic reuptake inhibitors
Animal research supports an emerging role for the noradrenaline system in impulse control. Given their potential to modulate prefrontal inhibitory processes, SNRIs may hold promise for the treatment of some types of impulsivity. Research findings indicate that SNRIs are effective in treating ADHD, a classic disorder of impulsivity, in the short to medium term. Atomoxetine, an SNRI, has demonstrated improvement in response inhibition in rats on a stop-signal analogue.10
One study in human volunteers demonstrated that atomoxetine improved impulsive action (using the stop-signal task) without affecting measures of attention and learning, whereas citalopram (an SSRI) affected learning but not attention or impulsive action.11 Similarly, improvements in impulse control were observed with venlafaxine in healthy controls using the 5-choice serial reaction time task.12
SNRIs may hold promise for helping individuals to stop impulsive behaviors. However, only a small amount of research exists regarding SNRIs for impulsivity, which seems to support their use in discrete areas. The SNRIs atomoxetine and desipramine have demonstrated improvement in the prototypical disorder of impulsivity, ADHD.13 Atomoxetine is FDA-approved for the treatment of ADHD in adults. Venlafaxine is less selective for the norepinephrine system, and findings for its efficacy as a treatment for ADHD have been mixed.14,15
In the area of other impulsive behaviors, there is little evidence for the use of SNRIs. The one exception is binge eating disorder. In a 10-week, double-blind, placebo-controlled trial of atomoxetine, the medication resulted in significant improvement in symptoms.16 Note that the data for atomoxetine and other noradrenergic agents, such as venlafaxine and desipramine, in substance addictions have been less convincing than one would suspect based on the preclinical results.17,18
The available data for SNRIs suggest that agents modifying noradrenaline may play a role in reducing impulsivity and improving the symptoms of ADHD. To what extent the currently available SNRIs differ from each other in these results, however, needs further inquiry. Finally, there have been no placebo-controlled trials of a noradrenergic agent in the treatment of most impulse control disorders, although this might be a promising area for future inquiry.
In our experience, ADHD is often comorbid with many other impulsive behaviors. Oftentimes, traditional stimulant medications, which tend to alter dopamine neurotransmission in the medial prefrontal cortex and nucleus accumbens, worsen impulsive behaviors. For example, we see that stimulants may worsen gambling and compulsive sexual behavior as well as hair pulling and skin picking. Therefore, a nonstimulant medication such atomoxetine (or another SNRI) may represent useful treatment options for ADHD and possibly for other impulsive behaviors as well. More clinical trials in this area would be valuable.
Opioid receptor antagonists inhibit dopamine release in the nucleus accumbens and ventral pallidum through the disinhibition of γ-aminobutyric acid input to the dopamine neurons in the ventral tegmental area. Preclinical study findings indicate opioid antagonists, such as naltrexone, reduce impulsive choice. Results from clinical studies on impulsivity, however, have been mixed. Naltrexone does not appear to reliably reduce impulsive choice, but it may enhance control of motor responses.19
Data support the use of the opioid antagonists naltrexone and nalmefene for the treatment of alcohol use disorders.20 Opioid antagonists have also shown promise in a variety of impulse control disorders, such as gambling disorder, kleptomania, and compulsive sexual behavior.21 Although the specific mechanisms by which opioid receptor antagonism ameliorated symptoms in specific patient groups, such as those with impulsivity, remain incompletely understood, 4 double-blind studies support the use of this class of medication for gambling disorder, and one double-blind study supports naltrexone for kleptomania.21,22 Gamblers with more severe urges to gamble exhibited a greater response to opioid antagonists than those with mild or no urges.23,24 The clinical use of naltrexone, however, is limited by concerns about liver enzyme elevations. This can be safely monitored by frequent blood tests and by limiting the use of concomitant NSAIDs.
Dr Grant is Professor in the department of psychiatry and behavioral neuroscience at the University of Chicago, Pritzker School of Medicine in Chicago. Dr Chamberlain is Clinical Lecturer in the department of psychiatry at the University of Cambridge, and Psychiatric Registrar at Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) in the UK.
1. Fineberg NA, Chamberlain SR, Goudriaan AE, et al. New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr. 2014;19:69-89.
2. Chamberlain SR, Fineberg NA. Fractionating impulsivity: commentary on “choice impulsivity” and “rapid-response impulsivity” articles by Hamilton and colleagues. Personal Disord. 2015;6:201-203.
3. Coccaro EF. Neurotransmitter correlates of impulsive aggression in humans. Ann N Y Acad Sci. 1996;794: 82-89.
4. Winstanley CA, Theobald DE, Dalley JW, Robbins TW. Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders. Neuropsychopharmacology. 2005;30:669-682.
5. Ye Z, Altena E, Nombela C, et al. Selective serotonin reuptake inhibition modulates response inhibition in Parkinson’s disease. Brain. 2014;137(pt 4):1145-1155.
6. Bartley CA, Bloch MH. Meta-analysis: pharmacological treatment of pathological gambling. Expert Rev Neurother. 2013;13:887-894.
7. Rothbart R, Amos T, Siegfried N, et al. Pharmacotherapy for trichotillomania. Cochrane Database Syst Rev. 2013;11:CD007662.
8. Coccaro EF, Lee RJ, Kavoussi RJ. A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder. J Clin Psychiatry. 2009;70:653-662.
9. Blanco C, Potenza MN, Kim SW, et al. A pilot study of impulsivity and compulsivity in pathological gambling. Psychiatry Res. 2009;167:161-168.
10. Chamberlain SR, Robbins TW. Noradrenergic modulation of cognition: therapeutic implications [published correction appears in J Psychopharmacol. 2013;27:964]. J Psychopharmacol. 2013;27:694-718.
11. Chamberlain, SR, Müller U, Blackwell AD, et al. Neurochemical modulation of response inhibition and probabilistic learning in humans. Science. 2006;311:861-863.
12. Humpston CS, Wood CM, Robinson ES. Investigating the roles of different monoamine transmitters and impulse control using the 5-choice serial reaction time task. J Psychopharmacol. 2013;27:213-221.
13. Faraone SV, Biederman J, Spencer T, et al. Attention-deficit/hyperactivity disorder in adults: an overview. Biol Psychiatry. 2000;48:9-20.
14. Ghanizadeh A, Freeman RD, Berk M. Efficacy and adverse effects of venlafaxine in children and adolescents with ADHD: a systematic review of non-controlled and controlled trials. Rev Recent Clin Trials. 2013;8:2-8.
15. Amiri S, Farhang S, Ghoreishizadeh MA, et al. Double-blind controlled trial of venlafaxine for treatment of adults with attention deficit/hyperactivity disorder. Hum Psychopharmacol. 2012;27:76-81.
16. McElroy SL, Guerdjikova A, Kotwal R, et al. Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-controlled trial. J Clin Psychiatry. 2007;68:390-398.
17. Tirado CF, Goldman M, Lynch K, et al. Atomoxetine for treatment of marijuana dependence: a report on the efficacy and high incidence of gastrointestinal adverse events in a pilot study. Drug Alcohol Depend. 2008;94:254-257.
18. Raby WN, Rubin EA, Garawi F, et al. A randomized, double-blind, placebo-controlled trial of venlafaxine for the treatment of depressed cocaine-dependent patients. Am J Addict. 2014;23:68-75.
19. Mitchell JM, Tavares VC, Fields HL, et al. Endogenous opioid blockade and impulsive responding in alcoholics and healthy controls. Neuropsychopharmacology. 2007;32:439-449.
20. Leeman RF, Bogart D, Fucito LM, Boettiger CA. “Killing two birds with one stone”: alcohol use reduction interventions with potential efficacy in enhancing self-control. Curr Addict Rep. 2014;1:41-52.
21. Grant JE, Schreiber LR, Odlaug BL. Phenomenology and treatment of behavioural addictions. Can J Psychiatry. 2013;58:252-259.
22. Yip SW, Potenza MN. Treatment of gambling disorders. Curr Treat Options Psychiatry. 2014;1:189-203.
23. Grant JE, Kim SW, Odlaug BL. A double-blind, placebo-controlled study of the opiate antagonist, naltrexone, in the treatment of kleptomania. Biol Psychiatry. 2009;65:600-606.
24. Grant JE, Kim SW, Hollander E, Potenza MN. Predicting response to opiate antagonists and placebo in the treatment of pathological gambling. Psychopharmacology (Berl). 2008;200:521-527.
25. Goracci A, di Volo S, Casamassima F, et al. Pharmacotherapy of binge-eating disorder: a review. J Addict Med. 2015;9:1-19.
26. Modesto-Lowe V, Van Kirk J. Clinical uses of naltrexone: a review of the evidence. Exp Clin Psychopharmacol. 2002;10:213-227.
27. Kalivas PW, McFarland K, Bowers S, et al. Glutamate transmission and addiction to cocaine. Ann N Y Acad Sci. 2003;1003:169-175.
28. Deepmala, Slattery J, Kumar N, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neurosci Biobehav Rev. 2015;55:294-321.
29. Jackson A, Nesic J, Groombridge C, et al. Differential involvement of glutamatergic mechanisms in the cognitive and subjective effects of smoking. Neuropsychopharmacology. 2009;34:257-265.
30. Nuijten M, Blanken P, van den Brink W, Hendriks V. Treatment of crack-cocaine dependence with topiramate: a randomized controlled feasibility trial in The Netherlands. Drug Alcohol Depend. 2014;138:177-184.
31. Guglielmo R, Martinotti G, Quatrale M, et al. Topiramate in alcohol use disorders: review and update. CNS Drugs. 2015;29:383-395.
32. Van Ameringen M, Mancini C, Patterson B, et al. A randomized, double-blind, placebo-controlled trial of olanzapine in the treatment of trichotillomania. J Clin Psychiatry. 2010;71:1336-1343.
33. Grant JE, Leppink EW. Choosing a treatment for disruptive, impulse-control, and conduct disorders. Curr Psychiatry. 2015;14:29-36. http://www.currentpsychiatry.com/index.php?id=31597&type=98&tx_ttnews[tt_news]=319697&cHash=da03e20e36. Accessed July 2, 2015.
34. Van den Eynde F, Senturk V, Naudts K, et al. Efficacy of quetiapine for impulsivity and affective symptoms in borderline personality disorder. J Clin Psychopharmacol. 2008;28:147-155.
35. Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med. 2014;174:1930-1933.
36. Price LH, Heninger GR. Lithium in the treatment of mood disorders. N Engl J Med. 1994;331:591-598.
37. Hollander E, Pallanti S, Allen A, et al. Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders? Am J Psychiatry. 2005;162:137-145.
38. Swann AC. Treatment of aggression in patients with bipolar disorder. J Clin Psychiatry. 1999;60(suppl 15):25-28.