Melissa M Dudas

Yale University, New Haven, CT, United States

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Publications (6)41.13 Total impact

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    ABSTRACT: Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (approximately 22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizophrenia. A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary outcome measures were continuous smoking abstinence in the last 4 weeks of the trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target quit date (TQD) (week 26). Smokers assigned to the BUP+TNP group (n = 29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than the PLO+TNP group (n = 29, 1/29, 3.4%) [Fisher's Exact Test, p < .05]; at 6-months post-TQD, 4/29 (13.8%) versus 0/29 (0.0%) achieved 7-day point prevalence smoking abstinence (p = .11). Neither bupropion SR nor smoking abstinence significantly altered the positive or negative symptoms of schizophrenia. The combination was well-tolerated in smokers with schizophrenia. Combination therapy with bupropion SR+TNP versus placebo+TNP is well-tolerated and significantly improved short-term smoking abstinence in smokers with schizophrenia.
    Biological psychiatry 06/2008; 63(11):1092-6. · 8.93 Impact Factor
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    ABSTRACT: Biochemical, physiological and genetic evidence suggests dysregulation of central nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychological performance in schizophrenia without the confounding effects of cigarette smoking, we compared neuropsychological performance in schizophrenia and healthy control nonsmokers after pre-treatment with the centrally-acting nAChR antagonist mecamylamine (MEC). Using a within-subjects, counterbalanced design, schizophrenia (n = 14) and control (n = 15) nonsmokers were pre-treated for 3 days with MEC (0.0, 5.0, and 10.0 mg/day). Subjects performed repeated neuropsychological assessments including visuospatial working memory (VSWM), Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Word Serial Position Test (WSPT) and Stroop Color Word Test (SCWT) during three sequential test sessions per week over three test weeks. We found significant main effects of schizophrenia diagnosis on: VSWM 30 and 60 delays (p's < 0.01), CPT (% Hit Rate, Reaction Time, Variability Index; p < 0.01 for all outcomes), WCST (p < 0.01 for all outcomes) and Word Serial Position Test (p < 0.01). However, there were no main effects of repeated test administration (Session) or MEC dose on any of these outcomes, and no significant 3-way (DiagnosisxSessionxMEC dose) interactions. Our results suggest that there are a broad range of neuropsychological deficits in nonsmokers with schizophrenia. Furthermore, pretreatment with a centrally-acting nAChR antagonist did not alter neuropsychological performance in either nonsmoking patients with schizophrenia or controls.
    Schizophrenia Research 07/2006; 85(1-3):213-21. · 4.59 Impact Factor
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    ABSTRACT: Cigarette smoking rates in schizophrenia are higher than in the general population. To determine whether cigarette smoking modifies cognitive deficits in schizophrenia and to establish the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related cognitive enhancement. Neuropsychological assessments were performed at smoking baseline, after overnight abstinence, and after smoking reinstatement across 3 separate test weeks during which subjects were pretreated in a counterbalanced manner with the nonselective nAChR antagonist mecamylamine hydrochloride (0, 5, or 10 mg/d). Twenty-five smokers with schizophrenia and 25 control smokers. Outpatient mental health center. Visuospatial working memory (VSWM) and Continuous Performance Test (CPT) scores. In smokers with schizophrenia and control smokers, overnight abstinence led to undetectable plasma nicotine levels and an increase in tobacco craving. While abstinence reduced CPT hit rate in both groups, VSWM was only impaired in smokers with schizophrenia. Smoking reinstatement reversed abstinence-induced cognitive impairment. Enhancement of VSWM and CPT performance by smoking reinstatement in smokers with schizophrenia, but not the subjective effects of smoking, was blocked by mecamylamine treatment. Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.
    Archives of General Psychiatry 07/2005; 62(6):649-59. · 13.77 Impact Factor
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    ABSTRACT: Rates of cigarette smoking in schizophrenia are higher than in the general population. To investigate differences in sensitivity to smoking cues between schizophrenia and control subjects, we compared smoking cue reactivity (CR) in schizophrenia versus control smokers with and without pretreatment with the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (MEC). Smoking CR in schizophrenia (n = 22) and nonpsychiatric control (n = 20) smokers was determined using exposure to smoking pictures. Three doses of MEC (0, 5, and 10 mg/day) were administered during the 3 test weeks to determine the role of nAChRs in mediating the smoking CR response. Eleven of 22 (50%) schizophrenia and 10 of 20 (50%) control smokers displayed smoking CR. Smoking CR was not significantly different between schizophrenia and control smokers in the placebo (0 mg/day) condition. However, MEC pretreatment produced a dose-dependent reduction of CR in schizophrenia smokers compared with placebo. There was no significant effect of MEC on CR in control smokers. Our findings suggest that blockade of CR by MEC may be more robust in schizophrenia versus control smokers, possibly due to reduced nAChR levels in the brains of patients with schizophrenia.
    Biological Psychiatry 05/2005; 57(7):802-8. · 9.25 Impact Factor
  • Melissa M Dudas, Tony P George
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    ABSTRACT: The smoking rate for patients with schizophrenia reaches as high as 90% in clinical samples, 70% for patients with bipolar disorder, and 40% to 50% for patients with major depression and anxiety disorders. Because it is a significant health hazard, smoking should be aggressively discouraged, and, in this group of patients, a combination of behavioral therapy and pharmacotherapy currently offers the best option. Nicotine provides a number of benefits, including anxiety relief, increased alertness, and improved cognitive functioning. It alters a wide range of central nervous system neurotransmitters. Unfortunately, nicotine readily establishes physiological dependence. In cessation efforts, transdermal nicotine patches and nicotine gum are helpful adjuncts. The primary FDA approved non-nicotine pharmacotherapy agent is bupropion (Zyban). Studies summarizing the effectiveness (or lack thereof) of other (off-label) agents, such as tricyclic antidepressants, MAO-Inhibitors, SSRIs, and clonidine, are cited.
    Essential psychopharmacology 02/2005; 6(3):158-72.
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    ABSTRACT: Schizophrenics have deficits in neuropsychological performance, some of which are modified by cigarette smoking. These patients also have high rates of smoking and resistance to smoking cessation interventions. We examined whether the presence of neuropsychological deficits prior to smoking cessation treatment was associated with smoking cessation treatment failure in schizophrenic as compared to non-psychiatric control smokers. Neuropsychological assessments were performed prior to treatment with pharmacological agents during the course of placebo-controlled trials in schizophrenic and non-psychiatric control smokers, and included the Wisconsin Card Sorting Test (WCST), a Visuospatial Working Memory (VSWM) task, the Stroop Color Word Test (SCWT) and the Continuous Performance Test (CPT). In schizophrenics (n=32), subjects who had greater deficits in VSWM and WCST performance were significantly less likely to quit smoking, but this association was not observed in controls (n=40). Differences between quitters and non-quitters were not likely related to atypical antipsychotic treatment or differences in depressive symptoms. No associations between baseline performance on CPT or SCWT and quit status were found in either group. These preliminary data suggest that in schizophrenics, neuropsychological deficits are associated with smoking cessation treatment failure.
    Schizophrenia Research 11/2004; 70(2-3):263-75. · 4.59 Impact Factor