Tuesday, January 29, 2019

Potent Dopamine D2 Antagonists Found to Block Reward-Enhancing Effects of Nicotine in Smokers With Schizophrenia

Many people with schizophrenia smoke cigarettes—a behavior that has been linked to worse symptoms and early mortality. A study in Schizophrenia Bulletin points to why some patients with schizophrenia who take certain antipsychotics may smoke more than patients with schizophrenia who take other antipsychotics. Chlorpromazine, fluphenazine, haloperidol, olanzapine, paliperidone, and risperidone may reduce some of the positive feelings that smokers associate with nicotine, the study suggests.

Previous studies have found that patients with schizophrenia who take first-generation antipsychotics, many of which block dopamine D2 receptors in the brain, have a hard time with smoking cessation, wrote Alexis E. Whitton, Ph.D., of McLean Hospital and colleagues. “Because these medications are foundational to the management of schizophrenia, an important question is whether dopamine D2 receptor antagonists modulate nicotine’s reinforcing effects.”

Whitton and colleagues recruited 184 chronic tobacco smokers with schizophrenia to examine the effects of smoking on reward learning (the process by which a behavior is modified based on prior reward). As part of the study, all participants performed a computer task where they had the chance to win money for correctly identifying differences between faces on a screen. Each participant performed this task before and after smoking a cigarette.

Of the 98 participants who completed the task, 71 reported taking chlorpromazine, fluphenazine, haloperidol, olanzapine, paliperidone, or risperidone (medications the authors noted are known to fully block dopamine D2 receptors) and 27 reported taking aripiprazole, clozapine, or quetiapine (medications that do not fully block dopamine D2 receptors). The researchers found that smoking increased reward learning in participants taking aripiprazole, clozapine, or quetiapine, but not in those taking the other antipsychotics.

“These findings point to a potential mechanistic explanation for increased smoking in individuals with schizophrenia who are treated with potent [dopamine] D2 receptor antagonists. Specifically, these antagonists appear to diminish the effects of tobacco smoking on reward processing,” Whitton and colleagues wrote. “Although not directly assessed in this study, we suggest that this may be a factor that drives compensatory increases in smoking behavior in order to achieve the same level of reward/stimulation.”

They continued, “Our findings have important clinical implications for treating individuals with schizophrenia and co-occurring nicotine dependence. All patients with schizophrenia should be advised to quit and offered pharmacologic assistance with quitting. If a patient is unable to quit with evidence-based cessation treatment and is taking a potent [dopamine] D2 receptor antagonist, switching to a different antipsychotic with lower affinity [dopamine] D2 antagonism (for example, clozapine) or partial [dopamine] D2 agonism (for example, aripiprazole) may be appropriate prior to a second trial of evidence-based cessation treatment.”

For related information, see the Psychiatric News article “Schizophrenia Patients Show Cognitive Improvements After Smoking Cessation” and the American Journal of Psychiatry study “Association Between Smoking Behavior and Cognitive Functioning in Patients With Psychosis, Siblings, and Healthy Control Subjects: Results From a Prospective 6-Year Follow-Up Study.”

(Image: iStock/Kim_white)

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