Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia

Independent Effects of Tobacco Abstinence and Bupropion
on Cognitive Function in Schizophrenia
A. Eden Evins, M.D., M.P.H.; Thilo Deckersbach, Ph.D.;
Corinne Cather, Ph.D.; Oliver Freudenreich, M.D.; Melissa A. Culhane, M.P.H.;
David C. Henderson, M.D.; Michael F. Green, Ph.D.; David A. Schoenfeld, Ph.D.;
Nancy A. Rigotti, M.D.; and Donald C. Goff, M.D.
Received Aug. 10, 2004; accepted March 7, 2005. From the Schizophrenia Program (Drs. Evins, Deckersbach, Cather, Freudenreich,Henderson, and Goff and Ms. Culhane), the Addictions ResearchProgram (Dr. Evins and Ms. Culhane), the Tobacco Treatment andResearch Center (Drs. Evins and Rigotti), and the Biostatistics Center(Dr. Schoenfeld), Massachusetts General Hospital, Boston; Harvard Objective: The objective of this study was
Medical School, Boston, Mass. (Drs. Evins, Deckersbach, Cather, to examine the effects of tobacco abstinence and Freudenreich, Henderson, Schoenfeld, Rigotti, and Goff); and the bupropion treatment on cognitive functioning in Department of Psychiatry and Biobehavioral Sciences, University of adult smokers with schizophrenia in the setting of California at Los Angeles, Los Angeles (Dr. Green). a randomized, double-blind, placebo-controlled This work was supported by a Young Investigator Award from the clinical trial of bupropion for smoking cessation.
National Alliance for Research on Schizophrenia and Affective Disorders,Great Neck, N.Y., by Department of Health and Human Services Method: Fifty-three adults with schizophrenia
Substance Abuse and Mental Health Services Administration grant (DSM-IV) took part in a trial of bupropion for 05B1MACMHS-04, and by National Institute on Drug Abuse grants RO3 smoking cessation. Subjects were enrolled in the DA12542 and K23 DA00510 (Dr. Evins); National Institute of Mental study from August 1999 to March 2003. Forty- Health grant K24 MH02025 (Dr. Goff); and National Heart, Lung, and five subjects remained in the trial at week 4; 41 Blood Institute grant K24 HL04440 (Dr. Rigotti). GlaxoSmithKline(Research Triangle Park, N.C.) provided sustained-release bupropion subjects, 19 taking bupropion and 22 taking pla- cebo, completed the baseline and week 4 cog- This work has been presented in part at the 9th annual meeting of nitive assessments and were included in the the Society for Research on Nicotine and Tobacco, New Orleans, La., analysis of adjusted effects of abstinence and Feb. 19–22, 2003, and the 156th annual meeting of the American bupropion treatment on cognitive function.
Psychiatric Association, San Francisco, Calif., May 17–22, 2003. Results: Controlling for bupropion treatment
Financial disclosure appears at the end of this article.
The authors acknowledge Dr. Kenneth Duckworth, M.D., and and baseline performance, 7 days of tobacco ab- Dr. Joan Kerzner, Ph.D., from the Massachusetts Department of stinence was associated with slowed motor speed Mental Health, Boston, for their support of the project. (finger tapping) but was not associated with Corresponding author and reprints: A. Eden Evins, M.D., worsening of performance on tests of attention MGH Schizophrenia Program, 25 Staniford Street, Boston, MA 02114 (AX Continuous Performance Test [AX-CPT]), (e-mail: a_eden_evins@hms.harvard.edu). verbal learning and memory (California VerbalLearning Test [CVLT]), working memory (digitspan), or executive function/inhibition (Stroop) igarette smoking is the leading preventable cause and was not associated with worsening of any Cof death in the United States, and 75% to 85%
clinical measures. Controlling for abstinencestatus, bupropion was associated with reduction of people with schizophrenia in the United States smoke, (improvement) in reaction time variability on compared with 23% of the general population.1–3 Despite the AX-CPT and with reduction in perseverative a 1996 American Psychiatric Association guideline rec- ommending routine treatment of smoking for patients Conclusion: We conclude that 1 week of to-
bacco abstinence is associated with slowed motor with psychiatric illness and preliminary reports of the speed but is not associated with detectable wors- safety and efficacy of pharmacologic approaches to smok- ening in performance on a range of neuropsycho- ing cessation in schizophrenia,4–10 physicians rarely ad- logical tests or clinical symptoms in the subset of vise patients with schizophrenia to quit smoking.11,12 patients who were able to quit smoking. We also In individuals without psychiatric illness, nicotine conclude that bupropion treatment may be associ-ated with improvement in variability of attention.
improves attention,13–18 learning, and memory19–23 and (J Clin Psychiatry 2005;66:1184–1190) has produced inconsistent effects on executive functionand inhibition as measured by the Stroop task.18,24,25Smoking abstinence for 24 hours26,27 and up to 5 days28has been found to worsen performance on attention tasks.
Hatsukami and colleagues26 reported increased mean re-action time, increased variability in reaction time, and in- creased errors of commission on an attention task in ado- general worsening in neuropsychological test perfor- lescent smokers deprived of cigarettes for 24 hours and mance, particularly in the domains of attention, learning, increased reaction time in smokeless tobacco users de- memory, and executive functioning. Given that nicotine prived of tobacco for 24 hours. In another study, 24 hours administration improves bradykinesia in smokers with of tobacco abstinence impaired recognition memory, at- schizophrenia,45,46 we also hypothesized that tobacco ab- tentional vigilance, and speed of target detection but not stinence would be associated with reduction in motor digit span recall, consistent with the hypothesis that to- speed on the finger tapping task. A secondary aim was bacco abstinence impairs episodic memory and sustained to assess the effect of tobacco abstinence on clinical attention, suggesting that some, but not necessarily all, symptomatology. Based on our previous finding that the short-term memory processes may not be influenced by changes in psychiatric symptoms in patients with schizo- phrenia during a quit attempt were mild and not clinically There has been a concerted effort in recent years to un- significant,4,47 our hypothesis was that tobacco abstinence derstand why people with schizophrenia use nicotine, would not be associated with significant exacerbation in with the hypothesis that this information may lead to new psychiatric symptoms. Another secondary aim was to as- treatments for both schizophrenia and nicotine depen- sess the effect of bupropion on cognitive function. Based dence.30 Consistent with results in the general population, on reports that bupropion is associated with improved at- nicotine has been shown to affect attention,31–33 reaction tentiveness in healthy males48 and patients with attention- time,34 delayed recognition,35 spatial organization,31,34 and deficit/hyperactivity disorder (ADHD)49–52 and depres- verbal memory34 in patients with schizophrenia. Nicotine sion,53 and is associated with improvement in negative transiently corrects some psychophysiologic deficits par- symptoms in the setting of a smoking cessation attempt,4,9 ticular to schizophrenia in smokers with schizophrenia our hypothesis was that bupropion treatment may be asso- who are deprived of cigarettes overnight and in non- ciated with improvement in attention in patients with smoking first-degree relatives of patients with schizo- phrenia.36–38 Nicotine also counteracts some adverse cog-nitive effects of conventional antipsychotic medications.31 Based on these findings, nicotine and nicotinic agonistshave been proposed as a potential therapy for cognitive The protocol was approved by the appropriate insti- tutional review boards. Subjects were recruited from ur- In the absence of data on the effect of tobacco absti- ban community mental health centers in Massachusetts nence on stability of cognitive and psychiatric symptoms, and were enrolled from August 1999 to March 2003. Ca- treaters may be reluctant to advise their patients with pacity to consent was determined and documented for all schizophrenia to attempt to quit smoking, due to concern participants by a doctoral-level clinician using a formal that tobacco abstinence may worsen cognitive function- process established in the Massachusetts General Hospi- ing or cause clinical destabilization. Several small studies tal (MGH) Schizophrenia Program. Eligible participants have examined the effect of tobacco abstinence on neuro- were adults who met DSM-IV criteria for schizophrenia psychological function and clinical symptoms in patients or schizoaffective disorder, depressive type, who smoked with schizophrenia, and the results have been inconsis- 10 or more cigarettes per day, wanted to try to quit smok- tent. Smoking cessation was associated with worsening of ing, had stable psychiatric symptoms in the judgment of performance on a visuospatial working memory task in their treating physician and had been receiving a stable patients with schizophrenia, independent of bupropion dose of antipsychotic medication for 30 days, did not treatment.40 Smoking reduction in the context of bupro- meet DSM-IV criteria for current major depressive disor- pion treatment was not associated with decreased perfor- der, and had a baseline Hamilton Rating Scale for Depres- mance on a cognitive battery in a small open study.41 sion (HAM-D) score < 20. Subjects with seizure disorder, Smoking reduction or cessation has been associated with history of bulimia, history of mania, or substance abuse mild exacerbation of psychotic symptoms after smoking disorder other than nicotine or caffeine within 6 months reduction or cessation in the absence of nicotine replace- of enrollment were not eligible. The smoking cessation ment or bupropion in 2 studies.4,42 Acute abstinence from study and outcomes are previously published.47 nicotine and longer-term smoking cessation were not as-sociated with symptom exacerbation in other studies.7,43,44 The primary purpose of this study was to examine the Participants were randomly assigned to receive bupro- effect of nicotine abstinence on neuropsychological test pion sustained release (SR) 150 mg or identical placebo performance in patients with schizophrenia in the setting tablets. Subjects took 1 tablet daily for 7 days, then 1 tab- of a randomized, double-blind, placebo-controlled study let twice daily for the remainder of the trial. A 1-week of the effect of bupropion on tobacco abstinence. Our hy- supply of study medications was distributed weekly; pothesis was that abstinence would be associated with a medication bottles and self-report of missed doses were collected at the weekly cognitive-behavioral therapy Symptoms (SANS)59 total score and 5 subscale scores, (CBT) group sessions. All participants received a 12- the Hamilton Rating Scale for Anxiety,60 the HAM-D,61 week, 12-session group CBT program that has been pre- the Positive and Negative Syndrome Scale (PANSS)62 viously described.4 All participants set a quit date 1 week total score and 5 subscale scores (positive, negative, ex- prior to the neuropsychological and clinical assessment.
citement, cognitive, depression/anxiety),63 the Simpson-Angus Scale,64 and the Barnes Akathisia Scale.65 Adverse events were recorded weekly using the Systematic As- Cognitive measures included an AX version of Con- sessment for Treatment-Emergent Events (SAFTEE).66 ners’ Continuous Performance Test (AX-CPT)54 to assess Four raters were trained on all measures, and adequate re- sustained attention. In this paradigm, participants are to press the space bar key as quickly as possible wheneveran “X” that was preceded by an “A” appears on the com- puter screen. Dependent variables are the ability to dis- Seven-day point prevalence abstinence at the time of criminate between targets (“X” and “distractor” letters), the assessments was defined as a self-report of smoking commission errors (not pressing “X” when it was pre- zero cigarettes in the past 7 days confirmed by an expired ceded by “A”), as well as the variability in reaction times air carbon monoxide (CO) measurement < 9 ppm.67 over time. The California Verbal Learning Test (CVLT),55 We used a series of linear regression models that a well-established measure of verbal learning and mem- included abstinence status, study medication status, and ory, was administered to assess memory for a list of baseline performance on cognitive and clinical outcome 16 shopping items presented orally in 5 trials, with free measures in order to evaluate the independent effects of recall after each trial. An interference list is presented tobacco abstinence and bupropion on cognitive and clini- following the fifth study-recall trial. Short- and long- cal outcomes as follows: outcome measure score = α + delayed (20 minutes) free recall of the first list was β1 (7-day point prevalence abstinence status) + β2 (drug assessed next, followed by a delayed recognition test.
group) + β3 (baseline score). An abstinence by medica- The CVLT provides measures of learning over 5 succes- tion status interaction term was tested for significance and sive trials (sum of the words recalled in trials 1–5), short- removed if it did not have a significant effect. Effects and long-delayed recall, and retention between short- were considered significant at a 2-sided p value of < .05.
and long-delayed recall and recognition to assess verballearning. Dependent variables in the present study were learning over the 5 learning trials, recognition, and per-severative errors (i.e., words that are recalled repeatedly).
After complete description of the study and provision The finger-tapping subtest of the Halstead-Reitan Neuro- of informed consent, 62 subjects were enrolled; 53 re- psychological Battery56 was used to assess motor speed ceived study medication and took part in a smoking cessa- (dependent variables: total scores for dominant and non- tion program. Of the 53 subjects, 45 were still participat- dominant hands). Subjects also completed a single trial ing at week 4, and 41 of these subjects completed the version of the Stroop57 as a measure of selective attention baseline and follow-up cognitive assessments and were and inhibition. In this version of the Stroop, subjects included in this analysis. Nineteen of the 41 subjects were are provided with neutral words (e.g., dog) and color taking bupropion, and 22 were taking placebo. Nine words (e.g., blue) on a computer screen. Neutral words (22%) of the 41 subjects achieved 7 days of abstinence are presented in a purple, red, blue, or green color. Color prior to the second assessment and 32 did not. Of the 9 words (purple, blue, red, green) are presented either in the subjects who were abstinent at week 4, 7 were in the bu- same color as the meaning of the word (blue presented propion group and 2 were in the placebo group. Those in blue = congruent condition) or in incongruent colors who did not achieve abstinence prior to the assessment (blue presented in red). Dependent measures were the re- had a mean 15.2% reduction in expired air CO with stan- action times for congruent, incongruent, and neutral con- dard deviation of 42.2 prior to the assessment. Those who ditions and facilitation and interference effects. We also were abstinent had an expired air CO measurement of < 9 administered the digit span subtest of the Wechsler Adult ppm and a self-report of smoking no cigarettes in the 7 Intelligence Scale, Third Edition (WAIS-III)58 to assess attention span and working memory (dependent vari- Subjects ranged in age from 24 to 63 years, reported ables: digits forward and backward). Tests of cognition smoking a mean of 29.3 (SD = 18.0; range, 10–100) cig- were administered at baseline and week 4.
arettes per day, and had a mean baseline CO measurementof 28.1 (SD = 15.7; range, 11–80) ppm. Mean PANSS score was 59.9 (SD = 13.3). Mean (SD) education was Clinical outcomes were assessed at baseline and week 11.7 (3.0) years, but subjects ranged from 4 to 17 years of 4 by the following: the Scale for Assessment of Negative education. There were no differences between abstinent Table 1. Baseline Characteristics of Adult Smokers With
Table 2. Adjusted Effects of Tobacco Abstinence and
Schizophreniaa
Bupropion Treatment on the Performance of Neurocognitive
Tests in Patients with Schizophrenia (N = 41)
aData are presented as mean (SD) unless otherwise indicated.
Baseline characteristics are not significantly different (p > .05).
bPatients who achieved tobacco abstinence for 7 days prior cDaily antipsychotic dose in chlorpromazine equivalents was calculated using the method of Woods.69 dAll patients were taking a stable dose of an antipsychotic medication for 30 days prior to and during the study.
Abbreviations: CO = carbon monoxide, CPT = Conners’ Continuous Performance Test, CVLT = California Verbal Learning Test, d' = signal-to-noise ratio, HAM-A = Hamilton Rating Scale for Anxiety, HAM-D = Hamilton Rating Scale for Depression, Effect estimates are controlled for abstinence status, bupropion PANSS = Positive and Negative Syndrome Scale, SANS = Scale treatment, and baseline performance.
for Assessment of Negative Symptoms.
Abbreviations: CPT = Conners’ Continuous Performance Test, CVLT = California Verbal Learning Test, d' = signal-to-noise ratio,SE = standard error.
and not-abstinent groups in demographic characteristicsor cognitive or clinical symptoms at baseline (Table 1).
dominant hands on the finger tapping task, controlling for Subjects in the bupropion group missed a mean (SD) of baseline finger tapping and bupropion treatment (Table 0.9 (.58) doses per week and subjects in the placebo group 2). Neither type nor dose of antipsychotic medication af- missed a mean (SD) of 0.9 (.60) doses per week by self- report, confirmed by pill count. Bupropion-treated sub- Seven days of tobacco abstinence was also associated jects were more likely to have achieved 1 week of con- with improvement in immediate recall of list A trials 1 tinuous abstinence prior to the assessment.
through 5 on the CVLT. Controlling for baseline perfor-mance and study medication assignment, we found that Effect of Abstinence on Cognitive Functioning subjects could remember 8.23 (95% CI = 0.5 to 15.97) Seven days of tobacco abstinence was associated with more words after 7 days of abstinence compared with significantly slowed motor speed for dominant and non- those who continued to smoke (p = .038) (Table 2). One week of abstinence was not associated with change in per- tween reduction in expired air CO and improvement in formance on the digit span or Stroop, but was associated CVLT performance and worsening in finger tapping in the with a trend toward increased distractibility as measured sample as a whole. Tobacco abstinence was not indepen- by variability of reaction times on the CPT, controlling for dently associated with change in clinical symptoms as bupropion treatment and baseline performance (Table 2).
measured by standard clinical rating scales.
Bupropion treatment was associated with significant This study also extends previous work by suggesting improvement in variability of reaction times on the CPT that bupropion is associated with improvement in atten- and reduction in perseverative errors on the CVLT, con- tion and memory in patients with schizophrenia. Nicotine trolling for abstinence status and baseline performance.
reduces (improves) reaction time variability associatedwith attention deficit in schizophrenia.31 We found that bupropion significantly improved this same measure of distractibility. This is consistent with reports that bupro- There was no significant effect of 7-day point preva- pion is associated with improved attentiveness in healthy lence abstinence on clinical measures after controlling for males48 and patients with ADHD49–52 and depression.53 smoking status and baseline symptoms. Likewise, there This finding must be interpreted cautiously, as the effect was no significant effect of bupropion on clinical mea- was seen on a single measure of attention, and there was sures after controlling for smoking status and baseline no apparent effect of bupropion on the d' measure of sig- values. All interactions between study medication and ab- nal to noise discrimination. Interestingly, abstinent sub- stinence status were not significant and were removed jects had a trend in the opposite direction, toward in- The findings are consistent with a report that substan- tial smoking reduction in patients with schizophrenia was not associated with worsening of verbal memory or atten- In the sample as a whole, there was a correlation be- tion.41 The findings are also not inconsistent with the re- tween percent change in expired air CO and change in to- port that improved working memory with chronic high tal recall (trials 1–5) on the CVLT (R = –0.405, p = .020) dose nicotine in rats persists for at least 2 weeks following and with change in finger tapping in the dominant hand nicotine discontinuation,68 because we cannot rule out (R = 0.42, p = .05). There were also correlations at a trend that nicotine may have beneficial effects on learning, level between percent change in CO and change in CPT memory, and attention that persist for longer than 7 days hit reaction time standard error (R = –0.248, p = .178) and after withdrawal of nicotine in patients with schizophre- change in Stroop reaction time on incongruent stimuli nia. These results should be confirmed in subjects who achieve sustained abstinence of several weeks or more. It Controlling for baseline performance and bupropion would also be useful to confirm these results in subjects treatment, associations remained between percent change randomly assigned to abstinence or, more practically, to a in CO and total recall (trials 1–5) on the CVLT (t = –2.52, nicotinic receptor antagonist. Although there were no dif- p = .017), change in tapping in the dominant hand (t = ferences in cognitive scores or clinical ratings at baseline 1.80, p = .089), and change in CPT hit reaction time stan- between those who achieved abstinence and those who dard error (t = –2.15, p = .041). The effect of change in did not, it is possible that subjects who are able to main- CO on change in Stroop reaction time was not significant tain abstinence for 7 days may be inherently less vulner- after controlling for bupropion treatment.
able to adverse cognitive effects of nicotine abstinence ormay have benefited less from nicotine.
Several issues limit our ability to generalize the asso- ciations detected between tobacco abstinence and cogni- In patients who were able to achieve abstinence in tive function in this study. The findings are limited by the a smoking cessation trial, 7 days of tobacco abstinence small number and nonrandom nature of patients achieving was associated with significantly slowed motor speed abstinence and the short duration of abstinence. The small as measured by the finger tapping task but was not as- number of patients that achieved abstinence for 7 days sociated with detectable worsening of performance on prior to the second assessment (N = 9) limits our power to neuropsychological tests of attention (AX-CPT), verbal detect differences that may be clinically important. As ab- learning and memory (CVLT), attention span and work- stinence was associated with a trend toward increased ing memory (digits forward and backward), or executive reaction time variability on the CPT, the effect of absti- function/inhibition (Stroop). Unexpectedly, abstinence nence on attention in particular should be further studied was independently associated with improved recall on the in a larger sample. With so few abstinent, the results may main outcome of the CVLT. The findings in abstinent sub- not be generalizable to the larger population of patients jects were supported with significant correlations be- with schizophrenia. It is also possible that nicotine is im- portant for visuospatial working memory40 and auditory of smoking in outpatients with psychiatric diagnoses. Nicotine Tob Res sensory gating37 in patients with schizophrenia, and that 13. Levin ED, Conners CK, Sparrow E, et al. Nicotine effects on adults the CVLT, CPT, digit span, Stroop task, and clinical rat- with attention-deficit/hyperactivity disorder. Psychopharmacology ing scales are less sensitive to these clinically important effects of nicotine abstinence.33 Alternatively, these find- 14. Levin ED, Conners CK, Silva D, et al. Transdermal nicotine effects on attention. Psychopharmacology (Berl) 1998;140:135–141 ings may challenge the widely held belief that smoking 15. Bates T, Mangan G, Stough C, et al. Smoking, processing speed and cessation will be harmful to the clinical stability of pa- attention in a choice reaction time task. Psychopharmacology (Berl) 16. Le Houezec J, Halliday R, Benowitz NL, et al. A low dose of sub- In conclusion, 7 days of tobacco abstinence was as- cutaneous nicotine improves information processing in nonsmokers.
sociated with reduction in motor speed but was not as- Psychopharmacology (Berl) 1994;114:628–634 sociated with worsening in performance on a range of 17. Gilbert DG, Estes SL, Welser R. Does noise stress modulate effects of smoking/nicotine? mood, vigilance, and EEG responses. Psychopharma- other neuropsychological tests or clinical symptoms in patients with schizophrenia who quit smoking, and there 18. Ernst M, Heishman SJ, Spurgeon L, et al. Smoking history and nicotine was some indication that bupropion treatment was associ- effects on cognitive performance. Neuropsychopharmacology 2001;25:313–319 ated with improvement in variability of attention. If con- 19. Warburton DM, Rusted JM, Fowler J. A comparison of the attentional firmed, these results may be a call to action to intensify and consolidation hypotheses for the facilitation of memory by nicotine.
the search for smoking cessation treatments that are effec- Psychopharmacology (Berl) 1992;108:443–447 20. Rusted J, Graupner L, Warburton D. Effects of post-trial administration of nicotine on human memory: evaluating the conditions for improvingmemory. Psychopharmacology (Berl) 1995;119:405–413 Drug names: bupropion (Zyban and others), chlorpromazine (Thora- 21. Rusted JM, Graupner L, Tennant A, et al. Effortful processing is zine, Sonazine, and others), clozapine (Clozaril, FazaClo, and others).
a requirement for nicotine-induced improvements in memory.
Psychopharmacology (Berl) 1998;138:362–368 Financial disclosure: Drs. Evins, Deckersbach, Henderson, Green, 22. Levin ED, Briggs SJ, Christopher NC, et al. Persistence of chronic Schoenfeld, and Goff and Ms. Culhane report no other financial affili- nicotine-induced cognitive facilitation. Behav Neural Biol 1992;58: ation or other relationship relevant to the subject matter of this article.
Dr. Cather has participated in speakers/advisory boards for Eli Lilly.
23. Levin ED, Christopher NC, Briggs SJ. Chronic nicotinic agonist and Dr. Freudenreich has received grant/research support from Pfizer. Dr.
antagonist effects on T-maze alternation. Physiol Behav 1997;61:863–866 Rigotti is a consultant for Pfizer and Sanofi-Aventis and has received 24. Foulds J, Stapleton J, Swettenham J, et al. Cognitive performance effects grant/research support from GlaxoSmithKline, Pfizer, and Sanofi- of subcutaneous nicotine in smokers and never-smokers. Psychopharma- 25. Perkins KA, Grobe JE, Fonte C, et al. Chronic and acute tolerance to subjective, behavioral and cardiovascular effects of nicotine in humans.
26. Hatsukami D, Fletcher L, Morgan S, et al. The effects of varying cigarette 1. de Leon J, Dadvand M, Canuso C, et al. Schizophrenia and smoking: deprivation duration on cognitive and performance tasks. J Subst Abuse an epidemiological survey in a state hospital. Am J Psychiatry 1995;152: 27. Keenan RM, Hatsukami DK, Anton DJ. The effects of short-term 2. de Leon J, Tracy J, McCann E, et al. Schizophrenia and tobacco smok- smokeless tobacco deprivation on performance. Psychopharmacology ing: a replication study in another US psychiatric hospital. Schizophr Res 28. Zack M, Belsito L, Scher R, et al. Effects of abstinence and smoking 3. Annual smoking-attributable mortality, years of potential life lost, and on information processing in adolescent smokers. Psychopharmacology economic costs: United States, 1995–1999. MMWR Morb Mortal Wkly 29. Hirshman E, Rhodes DK, Zinser M, et al. The effect of tobacco absti- 4. Evins AE, Mays VK, Rigotti NA, et al. A pilot trial of bupropion added nence on recognition memory, digit span recall, and attentional vigilance.
to cognitive behavioral therapy for smoking cessation in schizophrenia.
30. Dalack GW, Healy DJ, Meador-Woodruff JH. Nicotine dependence in 5. Chou KR, Chen R, Lee JF, et al. The effectiveness of nicotine-patch schizophrenia: clinical phenomena and laboratory findings. Am J Psychi- therapy for smoking cessation in patients with schizophrenia. Int J Nurs 31. Levin ED, Wilson W, Rose JE, et al. Nicotine-haloperidol interactions 6. Evins AE, Tisdale T. Bupropion and smoking cessation [letter]. Am J and cognitive performance in schizophrenics. Neuropsychopharmacology 7. Addington J, el-Guebaly N, Campbell W, et al. Smoking cessation 32. Depatie L, O’Driscoll GA, Holahan AL, et al. Nicotine and behavioral treatment for patients with schizophrenia. Am J Psychiatry 1998;155: markers of risk for schizophrenia: a double-blind, placebo-controlled, cross-over study. Neuropsychopharmacology 2002;27:1056–1070 8. Ziedonis DM, George TP. Schizophrenia and nicotine use: report of 33. Harris JG, Kongs S, Allensworth D, et al. Effects of nicotine on cognitive a pilot smoking cessation program and review of neurobiological and deficits in schizophrenia. Neuropsychopharmacology 2004;29:1378–1385 clinical issues. Schizophr Bull 1997;23:247–254 34. Smith RC, Singh A, Infante M, et al. Effects of cigarette smoking and 9. George TP, Vessicchio JC, Termine A, et al. A placebo controlled trial nicotine nasal spray on psychiatric symptoms and cognition in schizo- of bupropion for smoking cessation in schizophrenia. Biol Psychiatry phrenia. Neuropsychopharmacology 2002;27:479–497 35. Myers CS, Robles O, Kakoyannis AN, et al. Nicotine improves delayed 10. George TP, Ziedonis DM, Feingold A, et al. Nicotine transdermal patch recognition in schizophrenic patients. Psychopharmacology (Berl) 2004; and atypical antipsychotic medications for smoking cessation in schizo- phrenia. Am J Psychiatry 2000;157:1835–1842 36. Olincy A, Johnson LL, Ross RG. Differential effects of cigarette smoking 11. Williams JM, Ziedonis D. Addressing tobacco among individuals on performance of a smooth pursuit and a saccadic eye movement task in with a mental illness or an addiction. Addict Behav 2004;29: schizophrenia. Psychiatry Res 2003;117:223–236 37. Adler LE, Hoffer LD, Wiser A, et al. Normalization of auditory 12. Thorndike AN, Stafford RS, Rigotti NA. US physicians’ treatment physiology by cigarette smoking in schizophrenic patients. Am J phenidate in the treatment of attention-deficit hyperactivity disorder.
38. Adler LE, Hoffer LJ, Griffith J, et al. Normalization by nicotine of J Am Acad Child Adolesc Psychiatry 1995;34:649–657 deficient auditory sensory gating in the relatives of schizophrenics.
53. Becker RE, Dufresne RL. Perceptual changes with bupropion, a novel antidepressant. Am J Psychiatry 1982;139:1200–1201 39. Levin ED, Rezvani AH. Development of nicotinic drug therapy 54. Conners CK. The computerized continuous performance test.
for cognitive disorders. Eur J Pharmacol 2000;393:141–146 40. George TP, Vessicchio JC, Termine A, et al. Effects of smoking 55. Delis DC, Kramer JH, Kaplan E, et al. The California Verbal abstinence on visuospatial working memory function in schizophrenia.
Learning Test-Research Edition. New York, NY: Psychological 41. Weiner E, Ball MP, Summerfelt A, et al. Effects of sustained-release 56. Boll TJ. The Halstead-Reitan Neuropsychological Battery. In: bupropion and supportive group therapy on cigarette consumption Filskov SB, Boll TJ, eds. Handbook of Clinical Neuropsychology.
in patients with schizophrenia. Am J Psychiatry 2001;158:635–637 New York, NY: Wiley-Interscience; 1981:577–607 42. Dalack GW, Meador-Woodruff JH. Smoking, smoking withdrawal and 57. Perlstein WM, Carter CS, Barch DM, et al. The Stroop task and schizophrenia: case reports and a review of the literature. Schizophr Res attention deficits in schizophrenia: a critical evaluation of card and single-trial Stroop methodologies. Neuropsychology 1998;12:414–425 43. Dalack GW, Becks L, Hill E, et al. Nicotine withdrawal and psychiatric 58. Wechsler D. Wechsler Adult Intelligence Scale, Third Edition symptoms in cigarette smokers with schizophrenia. Neuropsychopharma- (WAIS-III). San Antonio, TX: Psychological Corporation; 1997 59. Andreasen N. Scale for the Assessment of Negative Symptoms (SANS).
44. Smith CM, Pristach CA, Cartagena M. Obligatory cessation of Iowa City, Iowa: University of Iowa; 1983 smoking by psychiatric inpatients. Psychiatr Serv 1999;50:91–94 60. Bech P, Kastrup M, Rafaelsen OJ. Mini-compendium of rating scales 45. Yang YK, Nelson L, Kamaraju L, et al. Nicotine decreases for states of anxiety depression mania schizophrenia with corresponding bradykinesia-rigidity in haloperidol-treated patients with DSM-III syndromes. Acta Psychiatr Scand Suppl 1986;326:1–37 schizophrenia. Neuropsychopharmacology 2002;27:684–686 61. Hamilton M. A rating scale for depression. J Neurol Neurosurg 46. Silver H, Shlomo N, Hiemke C, et al. Schizophrenic patients who smoke have a faster finger tapping rate than nonsmokers.
62. Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Eur Neuropsychopharmacol 2002;12:141–144 Scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276 47. Evins AE, Cather C, Deckersbach T, et al. A double-blind placebo- 63. Lindenmayer JP, Bernstein-Hyman R, Grochowski S, et al. Psycho- controlled trial of bupropion sustained-release for smoking cessation pathology of schizophrenia: initial validation of a 5-factor model.
in schizophrenia. J Clin Psychopharmacol 2005;25:218–225 48. Gobbi G, Slater S, Boucher N, et al. Neurochemical and psychotropic 64. Simpson GM, Angus JW. A rating scale for extrapyramidal effects of bupropion in healthy male subjects. J Clin Psychopharmacol side effects. Acta Psychiatr Scand Suppl 1970;212:11–19 65. Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry 49. Wilens TE, Prince JB, Spencer T, et al. An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and 66. Clyde DJ. SAFTEE: data system for side effect assessment scale.
bipolar disorder. Biol Psychiatry 2003;54:9–16 50. Wilens TE, Spencer TJ, Biederman J, et al. A controlled clinical trial 67. National Report on Human Exposure to Environmental Chemicals.
of bupropion for attention deficit hyperactivity disorder in adults. Am J Atlanta, GA: Centers for Disease Control and Prevention, National 51. Conners CK, Casat CD, Gualtieri CT, et al. Bupropion hydrochloride in 68. Levin ED. Nicotinic receptor subtypes and cognitive function.
attention deficit disorder with hyperactivity. J Am Acad Child Adolesc 69. Woods SW. Chlorpromazine equivalent doses for the newer 52. Barrickman LL, Perry PJ, Allen AJ, et al. Bupropion versus methyl- atypical antipsychotics. J Clin Psychiatry 2003;64:663–667

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