Varenicline plus healthy lifestyle intervention for smoking cessation in psychotic disorders
Chair of Psychiatry, St. Vincent’s Hospital and The University of Melbourne, Fitzroy, Victoria, Australia
National Health and Medical Research Council Senior Research Fellow, Centre for Brain and Mental Health Research, University of Newcastle
Newcastle, New South Wales, Australia
School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia
Monash Alfred Psychiatry Research Centre, Monash University, Prahran, Victoria, Australia
Clarendon Community Mental Health, St. Vincent’s Health, East Melbourne, Victoria, AustraliaAndrew J. Pirola-Merlo, BSc (Hons), PhD
Adjunct Associate Professor, Faculty of Business and Economics, Monash University, Caulfield, Victoria, Australia
BACKGROUND: We were interested in exploring the efficacy and safety of varenicline as an adjunct to a healthy lifestyle intervention for smoking cessation among individuals with a severe mental illness.
METHODS: We used varenicline as an adjunct to a healthy lifestyle intervention in 14 smokers with a psychotic illness.
RESULTS: Overall, smoking cessation rates were 36% at 3 months and 42% at 6 months. The most commonly reported side effects were sleep disturbance and nausea. These tended to occur early in treatment, and patients responded to general measures of support and reassurance. Of the 14 participants, 1 dropped out because of psychiatric problems and 2 because of other side effects.
CONCLUSIONS: Varenicline appears to be an effective adjunct to a healthy lifestyle intervention for smokers with a psychotic illness. Although the results of this open study are encouraging, replication in an adequately powered, randomized controlled trial is required before definitive conclusions can be drawn.
KEYWORDS: schizophrenia, bipolar disorder, smoking cessation, cognitive-behavioral therapy, varenicline
ANNALS OF CLINICAL PSYCHIATRY 2012;24(4):285-291
Rates of cigarette smoking among the general population in many Western countries have declined significantly over the past 20 years in association with successful public awareness campaigns and antismoking legislation. Individuals with mental illness do not seem to have benefited from these general approaches, because very high rates of smoking persist in those with severe illnesses such as schizophrenia.1,2 This trend remains after controlling for socioeconomic factors. Smoking is associated with serious morbidity, lower quality of life, and earlier mortality among persons with psychosis compared with the general community. Individuals with psychotic illness who are at significant risk for cardiovascular disease, obesity, and diabetes are particularly in need of effective smoking cessation interventions.3
To assist cessation in smokers with psychosis, investigators have evaluated combinations of psychological and pharmacologic interventions,4 including individual- and group-based psychoeducation,5 nicotine replacement,6,7 bupropion,8,9 and bupropion with nicotine replacement.10-12 Our work in this field set the foundation for the current study.
In a large controlled trial, Baker et al13,14 randomly assigned 298 heavy smokers with a psychotic disorder to treatment as usual or an 8-session, individually administered intervention (nicotine replacement therapy [NRT] and cognitive-behavioral therapy). Compared with controls, a significantly higher proportion of smokers who completed all treatment sessions had stopped smoking at 12 months (point prevalence abstinence, 19% vs 7%, respectively).
In a subsequent open trial, we15,16 produced and piloted a more comprehensive treatment program for individuals with psychosis—the “Healthy Lifestyles” program—which addresses diet and exercise as well as cigarette smoking. Treatment sessions over 3 months were offered to all participants after a baseline assessment, with follow-up at 15 weeks. Four sites recruited 43 participants. A statistically significant reduction in smoking occurred between pre- and post-treatment, with 19% point prevalence abstinence at post-treatment assessment. The average number of cigarettes smoked per day was reduced from 31 to 17 (P < .001). These data are encouraging, but abstinence rates of 19% still leave many individuals with schizophrenia with a problematic smoking habit, and new pharmacologic interventions have the potential to enhance abstinence rates.
Varenicline has proven efficacy for smoking cessation in randomized controlled trials (RCTs) when compared with placebo, NRT, and bupropion.17-21 Varenicline binds with the α4β2 neuronal nicotinic acetylcholine receptor, where it acts as a partial agonist. Its binding both alleviates symptoms of craving and withdrawal and reduces the rewarding and reinforcing effects of smoking by preventing nicotine binding to α4β2 receptors. However, serious concerns have been raised about varenicline’s potential psychiatric effects, with depression and suicide being the most well-publicized.22 The perceived risk of these outcomes probably is exaggerated,23 but a high degree of concern about this agent’s use in persons with mental illness remains in the minds of clinicians and patients. Furthermore, single case reports have suggested the potential of varenicline to worsen psychotic symptoms in some individuals with schizophrenia24 and induce mania in some individuals with bipolar disorder (BD).25
The study reported here was aimed at exploring the efficacy and safety of varenicline as an adjunct to a psychosocial intervention in persons with schizophrenia, schizoaffective disorder, or BD. Our hypothesis was that varenicline plus participation in the “Healthy Lifestyles” program would be effective and well tolerated as a smoking cessation intervention among persons with psychotic disorders.
We conducted an open trial of varenicline plus our established “Healthy Lifestyles” intervention among persons with psychotic disorders. Participants were recruited through case managers at the 2 community mental health centers associated with St. Vincent’s Mental Health Service, Melbourne, Australia. Our target was 15 participants, based on pragmatics of funding and follow-up; 1 declined to participate after screening, leaving a total of 14.
We enrolled individuals age ≥18 with a diagnosis of a psychotic disorder (schizophrenia, schizoaffective disorder, or BD), based on the Mini International Neuropsychiatric Interview.26 Enrollees had been on stable psychiatric medication for ≥3 months and were current heavy smokers (≥15 cigarettes per day).
Exclusion criteria included non-psychotic illness, smoking <15 cigarettes per day, non-English speaking; organic brain disease; an unstable psychiatric condition (eg, actively suicidal as per clinical judgment) or medical condition (eg, uncontrolled diabetes), or any specific contraindication to varenicline (apart from having a mental illness).
All assessment instruments are widely used in mental health and/or tobacco treatment research and practice. Demographic characteristics and previous treatment history were collected from participants at the initial assessment. The following instruments were administered at each weekly visit:
Tobacco use: Opiate Treatment Index27 to estimate average daily use of tobacco; the Fagerström Test for Nicotine Dependence28; expired carbon monoxide, using a Bedfont Smokerlyzer; and the Minnesota Nicotine Withdrawal Scale–Revised (self and observer ratings).29
Psychiatric Symptomatology: Brief Psychiatric Rating Scale (BPRS),30 a well-validated measure of psychotic symptoms; Beck Depression Inventory (BDI),31 a well-validated self-report measure of depressed mood, with a specific item on suicidality; and the Young Mania Rating Scale (YMRS),32 a widely used and validated assessment of manic symptomatology.
Side effects: At each visit, participants were asked if they have experienced any symptoms that they considered to be varenicline side effects; they also filled out our standardized side effect checklist (available upon request from the authors).
Safety checks: To ensure patient safety, we added specific safety monitoring, including the Columbia Suicide Severity Rating Scale at each weekly visit. In addition, between each study visit the therapist delivering the intervention (D.H.) made telephone contact with each participant, as a quick wellbeing check.
Formal assessments were conducted at baseline and at 3 and 6 months by trained research assistants who were not involved in delivering the intervention and did not have prior knowledge of the participants. Each participant was offered $30 for the initial assessment and each post-treatment assessment as reimbursement for time and out-of-pocket expenses (ie, travel, parking fees). All procedures were approved by the St. Vincent’s Hospital (Melbourne) Human Research Ethics Committee.
a) The nonpharmacologic component: The intervention, adapted from our established manual-guided “Healthy Lifestyles” program,15,16 was delivered as 6 weekly, 1-hour sessions, followed by three 1-hour booster sessions at weeks 8, 10, and 12. Therapy components included case formulation and feedback from assessment, psychoeducation, motivation enhancement, mood/craving monitoring, mindfulness training, cognitive restructuring, identifying and managing unhelpful automatic thought patterns, enhancement of non-smoking related activities, pleasant events scheduling, coping with cigarette cravings, problem-solving, refusal skills, and relapse prevention and/or management. During each therapy session, discussion and skills practice focused on unhealthy behaviors the participant identified as most important/problematic. The therapist took the opportunity to integrate messages/skill development about other lifestyle factors as appropriate. Self-help material was provided throughout the treatment period, related to the unhealthy lifestyle behavior discussed in the session. The therapist delivering the intervention (D.H.) was experienced in the “Healthy Lifestyles” program intervention and received training and weekly supervision from Dr. Baker.
b) The pharmacologic component: Varenicline was provided to participants at each visit. Dose titration was: 0.5 mg/d for days 1 to 3; 1 mg/d for days 4 to 7; and 2 mg/d (the target dose) from days 8 to 84.
TABLE 1 provides a synopsis of the age, sex, and primary psychiatric diagnoses of the intervention group, as well as the most prominent reported side effects. The most common side effects were sleep disturbance and nausea.
Demographic and illness profile, cigarettes smoked, and main side effects of varenicline in 14 patients with psychotic illness
||Cigarettes smoked per day at entry
||Cigarettes smoked per day at 3 months
||Cigarettes smoked per day at 6 months
||Main reported side effects
||Increased appetite, vivid dreams, headache
||Insomnia, vivid dreams, increased appetite
||Blurred vision, dry mouth, fatigue, thirst, dizziness, nausea
||Poor concentration, increased appetite, abnormal dreams, transient depression
||Nausea; stopped varenicline after 3 months
||Bipolar I disorder with psychosis
||Dry mouth, nausea, sweating
||Bipolar I disorder with psychosis
||Constipation, headache, abnormal dreams
||Bipolar I disorder with psychosis
||Nausea, vomiting; stopped varenicline after 2 weeks
||Abnormal dreams, constipation
||Bipolar disorder with psychosis
||Depression with suicidality; withdrew after a few days
||Dry mouth, thirst
One patient with severe, recurrent BD with psychosis dropped out because of psychiatric issues. She experienced depressed mood, agitation, and irritability along with suicidal ideation and ceased the medication after 4 days. Her psychiatric symptoms stabilized within 1 week, and she continued smoking approximately 25 cigarettes a day. Another patient, who had successfully ceased smoking, stopped varenicline after 3 weeks because of constipation but recommenced it after his urge to smoke worsened and he feared a return to smoking. Two additional patients ceased medication because of ongoing nausea—1 at 3 weeks, and 1 at 3 months.
After 6 months of the intervention, cigarettes smoked per day was significantly reduced, and 6 patients achieved carboxymeter-confirmed abstinence (TABLE 2). Analysis of only those who were not abstinent at 6-months follow-up showed a significant reduction in number of cigarettes smoked per day. Of interest was that, although observer-rated nicotine withdrawal increased from baseline to 6-month follow-up (P < .05), patients self-reported a decrease in this rating (P=.02). No significant changes from baseline to follow-up were observed on the BDI (pre: 9.2 [SD 7.0], post: 8.1 [SD 8.1]); YMRS (pre: 3.8 [SD 5.5], post 4.9 [SD 6.0]); or BPRS (pre: 35.6 [SD 5.0], post: 39.8 [SD 8.9]).
Baseline and post-treatment (6-month) ratings
||After treatment (6-month follow-up)
||95% CI of difference
|Cigarettes per day
||15 to 40
||0 to 40
|Cigarettes per day (excluding abstainers post-treatment)
||15 to 40
||4 to 40
|Carboxymeter (CO ppm)
||10 to 77
||2 to 60
||2 to 10
||1 to 10
||.25 to 1.75
||0 to 2.25
||0 to 2.33
||.11 to 1.78
This open study demonstrated that varenicline, in association with a comprehensive healthy lifestyle intervention, was associated with a substantial decrease in cigarette smoking among a heterogeneous group of patients with psychotic disorders. Abstinence was achieved in 42% of the participants at the 6-month mark. Side effects were mostly nonpsychiatric (ie, sleep disturbance, nausea) and transient; 1 patient with BD dropped out because of a severe worsening of depression with suicidality.
Some published studies have assessed the use of varenicline in persons with a mental illness. In a pre-approval trial by Stapleton et al,33 varenicline appeared to be effective and well tolerated by patients in a pre-post comparison with NRT. However, that study and its nonpharmacologic intervention were not tailored to persons with a mental illness, and only 7 patients (0.2% of the sample) had a psychotic illness.
Purvis et al34 performed a retrospective review of 50 military veterans who had received varenicline. Overall, 30% quit smoking, and 70% failed either because of lack of effectiveness or inability to tolerate varenicline. The proportion of those with a mental illness was higher in the failure group vs the success group (57% vs 27%, respectively; P < .001. All 4 of the patients who discontinued because of mood and behavioral problems had an established mental illness.
McClure et al35 analyzed smoking outcomes and side effects associated with varenicline in attendees at a smoking cessation clinic. Participants with a probable history of major depression were more likely than those without a history to report tension/agitation, irritability/anger, confusion, or depression at 21 days (P < .05) and depression and anxiety at 3 months (P < .01); however, smoking cessation rates did not differ between the groups.
In a study of varenicline in 14 patients with schizophrenia and schizoaffective disorder, Smith et al36 reported no significant exacerbations in psychopathology ratings. Side effects included nausea, dry mouth, sleepiness, and shaking; 2 patients discontinued treatment, and 9 of the remaining 12 reduced the number of cigarettes smoked, although only 1 was abstinent at the end of the trial.
Finally, Weiner et al37 performed a double-blind, placebo-controlled trial of varenicline in 9 patients with schizophrenia or schizoaffective disorder and found no worsening of psychotic symptoms. Constipation, nausea, and insomnia were reported side effects. Varenicline was associated with a reduction in smoking.
The study presented here demonstrated that the combination of a comprehensive healthy lifestyle/smoking cessation intervention delivered by trained mental health staff can, in conjunction with varenicline, produce smoking abstinence rates of 36% at 3 months (while still on varenicline) and 42% 3 months later, having ceased the medication. This is higher than we reported in our studies with similar patients, using an identical intervention but with NRT (abstinence rate 19%). Furthermore, despite this being a psychiatrically high-risk group, only 1 participant dropped out because of worsening psychiatric symptoms, albeit that it was not clear whether these were directly exacerbated by the varenicline.
The findings regarding psychiatric adverse events are compatible with those reported by McClure et al35 in patients with depression. Indeed, overall in our study, the side effect profile was similar to that experienced by persons without a mental illness who cease smoking. Two patients ceased medication because of nausea and resumed smoking at baseline rates; 1 patient dropped out because of constipation but restarted varenicline because he feared starting smoking again. It is also worth noting that smoking cessation has been associated with depression, notably in people with a history of depression.38
This study has limitations, notably the small number of participants and the fact that we did not control for multiple testing on outcome measures. The heterogeneity of diagnoses also is a drawback, although it allowed a more “real life” clinical sample than would be usual in RCTs. We did not include a control group, but could make some comparisons with the outcomes from previous studies using NRT, as the participant sample was similar and the nonpharmacologic intervention was manualized and has high fidelity. Of course, randomized controlled comparison trials will more definitively determine the superiority or otherwise of varenicline vs NRT in this patient group. Also, longer-term outcome studies are required to determine relapse rates and guide duration of therapy. Including measures of varenicline’s effects on neurobiological markers and cognitive functioning would be useful to better characterize the mechanisms that drive so many people with schizophrenia to smoke. A recent randomized placebo-controlled trial39 showed varenicline to be associated with reduced sensory P50 gating, startle reactivity, and antisaccade errors in persons with schizophrenia.
At this stage, we believe it is reasonable to conclude that varenicline can be effective in reducing smoking in individuals with severe mental illness, in conjunction with a comprehensive psychosocial intervention. Most side effects are tolerable and are similar to those experienced by persons without a mental illness. However, because of the potential for worsening of psychiatric symptoms in high-risk patients, we suggest that varenicline be used with careful and comprehensive mental state monitoring, expressly for depressive symptoms and suicidality. Although results of the current open study are encouraging, replication in an adequately powered RCT is required before definitive conclusions can be drawn.
DISCLOSURES: Dr. Castle has received grant support from Allergan, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Hospira, Janssen-Cilag, Lundbeck, Pfizer, and Roche; has been a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Hospira, Janssen Cilag, Lundbeck, Organon, Pfizer, sanofi-aventis, and Wyeth; served as an advisory board member for AstraZeneca, Janssen-Cilag, Lundbeck, Pfizer, and Wyeth; and currently serves on the Australian Varenicline Advisory Board (Pfizer). Drs. Baker, Richmond, and Pirola-Merlo, Ms. Filia, and Ms. Harris report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
ACKNOWLEDGEMENTS: Funding and supply of varenicline for this study was provided by Pfizer Australia Pty Ltd as part of an investigator-initiated study. The company had no input into the design, analysis, or write-up of the study, and no individual involved in the study received any financial or other incentive regarding the study. The authors would like to thank Kate Filia for assistance with follow-up assessments, Charlotte Ross-Harris for assisting with data entry, Jill Williams for assistance with study design, and Jayashri Kulkarni and Anthony de Castella for their support.
- Jablensky A, McGrath J, Herrman H, et al. Psychotic disorders in urban areas: an overview of the study on low prevalence disorders. Aust N Z J Psychiatry. 2000;34:221–236.
- Kelly DL, McMahon RP, Wehring HJ, et al. Cigarette smoking and mortality risk in people with schizophrenia. Schizophr Bull. 2011;37:832–838.
- Baker A, Ivers RG, Bowman J, et al. Where there’s smoke, there’s fire: high prevalence of smoking among some sub-populations and recommendations for intervention. Drug Alcohol Rev. 2006;25:85–96.
- El-Guebaly N, Cathcart J, Currie S, et al. Smoking cessation approaches for persons with mental illness or addictive disorders. Psychiatr Serv. 2002;53:1166–1170.
- Addington J, el-Guebaly N, Campbell W, et al. Smoking cessation treatment for patients with schizophrenia. Am J Psychiatry. 1998;155:974–976.
- Ziedonis DM, George TP. Schizophrenia and nicotine use: report of a pilot smoking cessation program and review of neurobiological and clinical issues. Schizophr Bull. 1997;23:247–254.
- George TP, Ziedonis DM, Feingold A, et al. Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia. Am J Psychiatry. 2000;157:1835–1842.
- Evins AE, Mays VK, Rigotti NA, et al. A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. Nicotine Tob Res. 2001;3:397–403.
- George TP, Vessicchio JC, Termine A, et al. A placebo controlled trial of bupropion for smoking cessation in schizophrenia. Biol Psychiatry. 2002;52:53–61.
- Evins AE, Cather C, Culhane MA, et al. A 12-week double-blind, placebo-controlled study of bupropion SR added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia. J Clin Psychopharmacol. 2007;27:380–386.
- Evins AE, Cather C, Deckersbach T, et al. A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. J Clin Psychopharmacol. 2005;25:218–225.
- George TP, Vessicchio JC, Sacco KA, et al. A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. Biol Psychiatry. 2008;63:1092–1096.
- Baker A, Richmond R, Haile M, et al. A randomized controlled trial of a smoking cessation intervention among people with a psychotic disorder. Am J Psychiatry. 2006;163:1934–1942.
- Baker A, Richmond R, Haile M, et al. Characteristics of smokers with a psychotic disorder and implications for smoking interventions. Psychiatry Res. 2007;150:141–152.
- Baker A, Richmond R, Castle D, et al. Coronary heart disease risk reduction intervention among overweight smokers with a psychotic disorder: pilot trial. Aust N Z J Psychiatry. 2009;43:129–135.
- Baker A, Kay-Lambkin FJ, Richmond R, et al. Study protocol: a randomised controlled trial investigating the effect of a healthy lifestyle intervention for people with severe mental disorders. BMC Public Health. 2011;11:10.
- Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006;296(1):47–55.
- Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006;296:56–63.
- Nides M, Oncken C, Gonzales D, et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006;166:1561–1568.
- Tonstad S, Tønnesen P, Hajek P, et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006;296:64–71.
- Williams KE, Reeves KR, Billing CB Jr, et al. A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Curr Med Res Opin. 2007;23:793–801.
- Kuehn BM. FDA warns of adverse events linked to smoking cessation drug and antiepileptics. JAMA. 2008;299:1121–1122.
- Gunnell D, Irvine D, Wise L, et al. Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database. BMJ. 2009;339:b3805.
- Freedman R. Exacerbation of schizophrenia by varenicline. Am J Psychiatry. 2007;164:1269.
- Kohen I, Kremen N. Varenicline-induced manic episode in a patient with bipolar disorder. Am J Psychiatry. 2007;164:1269–1270.
- Lecrubier Y, Sheehan DV, Weiller E, et al. The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry. 1997;12:224–231.
- Darke S, Hall W, Wodak A, et al. Development and validation of a multi-dimensional instrument for assessing outcome of treatment among opiate users: the Opiate Treatment Index. Br J Addict. 1992;87:733–742.
- Heatherton TF, Kozlowski LT, Frecker RC, et al. The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. Br J Addict. 1991;86:1119–1127.
- Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986;43:289–294.
- Ventura J, Lukoff D, Nuechterlein KH, et al. Brief Psychiatric Rating Scale. Expanded version (4.0). Scales, anchor points, and administration manual. Int J Methods Psychiatr Res. 1993;3:227–243.
- Beck AT, Steer RA, Brown GK. BDI-II Beck Depression Inventory Manual. 2nd ed. San Antonio TX: Harcourt, Brace & Company; 1996.
- Young RC, Biggs JT, Ziegler VE, et al. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429–435.
- Stapleton JA, Watson L, Spirling LI, et al. Varenicline in the routine treatment of tobacco dependence: a pre-post comparison with nicotine replacement therapy and an evaluation in those with mental illness. Addiction. 2008;103:146–154.
- Purvis TL, Mambourg SE, Balvanz TM, et al. Safety and effectiveness of varenicline in a veteran population with a high prevalence of mental illness. Ann Pharmacother. 2009;43:862–867.
- McClure JB, Swan GE, Jack L, et al. Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline. J Gen Intern Med. 2009;24:563–569.
- Smith RC, Lindenmayer JP, Davis JM, et al. Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder. Schizophr Res. 2009;110:149–155.
- Weiner E, Buchholz A, Coffay A, et al. Varenicline for smoking cessation in people with schizophrenia: a double blind randomized pilot study. Schizophr Res. 2011;129:94–95.
- Covey LS, Glassman AH, Stetner F. Major depression following smoking cessation. Am J Psychiatry. 1997;154:263–265.
- Hong LE, Thaker GK, McMahon RP, et al. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 2011;68:1195–1206.
CORRESPONDENCE: David Castle, MSc, MD, FRCPsych, FRANZCP, Chair of Psychiatry, St. Vincent’s Hospital and The University of Melbourne, 46 Nicholson Street, Fitzroy, Victoria 3065 Australia E-MAIL: firstname.lastname@example.org
Annals of Clinical Psychiatry ©2012 Frontline Medical Communications.