Introduction
Cigarette smoking remains the primary cause of preventable death and morbidity in the United States. This problem is graver still in patients with substance use disorders (SUDs) and mental health disorders (MHDs). Patients with SUDs, particularly alcohol dependence, are two to three times more likely to smoke cigarettes than the general population (Bobo, Reference Bobo1989). These patients are both more nicotine dependent (Hughes & Kalman, Reference Hughes and Kalman2006) and prone to greater nicotine withdrawal symptoms (Marks, Hill, Pomerlaeau, Mudd & Blow, Reference Marks, Hill, Pomerleau, Mudd and Blow1997) compared to the general population. In fact, the lifetime smoking cessation rate for individuals with alcohol dependence is merely 7% as opposed to 49% in the general population (DiFranza & Guerrera, Reference DiFranza and Guerrera1990). These individuals are also at greater risk of health complications from concomitant use of cigarettes and alcohol (Vaillant, Schnurr, Baron & Gerber, Reference Vaillant, Schnurr, Baron and Gerber1991).
Similarly, smokers with MHDs also use cigarettes at greater rates (Lasser, Boyd, Woolhandler, Himmelstein, McCormick & Bor, Reference Lasser, Boyd, Woolhandler, Himmelstein, McCormick and Bor2000) and are more heavily nicotine dependent (Dani & Harris, Reference Dani and Harris2005). These patients may suffer more severe withdrawal and negative mood during cessation attempts (Xian et al., Reference Xian, Scherrer, Madden, Lyons, Tsuang and True2005) and tend to rely on cigarettes as a form of self-medication (Pomerleau, Marks, & Pomerleau, Reference Pomerleau, Marks and Pomerleau2000), contributing to poor smoking cessation outcomes (Diaz, Rendon, Velasquez, Susce & de Leon, Reference Diaz, Rendon, Velasquez, Susce and de Leon2006) and a higher rate of smoking-caused illnesses (Baker et al., Reference Baker, Richmond, Haile, Lewin, Carr and Taylor2006; Lawrence, Holman, Jablensky & Hobbs, Reference Lawrence, Holman, Jablensky and Hobbs2003). The concurrence of problems in SUD and MHD patients suggest that smokers with both represent a subset of the general population that are both highly resistant to anti-smoking intervention and prone to significant smoking-related medical sequelae. There continues to be very little literature published in this area as such.
While bupropion and nicotine replacement therapies, alone or in combination with counselling, have proven to be useful for a number of patients; they fail frequently to achieve the desired results (Gonzales et al., Reference Gonzales, Rennard, Nides, Oncken, Azoulay and Billing2006; Jorenby et al., Reference Jorenby, Hays, Rigotti, Azoulay, Watsky and Williams2006; Masuhara, Heath & Okoli, Reference Masuhara, Heath and Okoli2013). These regulatory studies are conducted in smokers without major medical, psychiatric or addictive comorbidity. Therefore it is unclear regarding the actual effectiveness of these agents in treating smokers who are also psychiatrically impaired and also addicted to other substances.
Varenicline is another smoking cessation drug with FDA approval in non-comorbid smokers that is a highly selective nicotine partial agonist (Oncken et al., Reference Oncken, Gonzales, Nides, Rennard, Watsky and Billing2006; Henningfield, Fant, Buchhalter & Stitzer, Reference Henningfield, Fant, Buchhalter and Stitzer2005). Unfortunately, there have been reports of serious neuropsychiatric decompensation and increased suicidality (‘CHANTIX® (varenicline) tablets’, 2012) among patients receiving varenicline treatment. Theoretically, this makes it more risky to use in a mentally ill, chemically abusing patient population. These facts make the prescriber weigh the risk of nicotine addiction and medical morbidity and mortality against a potentially lethal psychiatric decompensation.
We report here a retrospective case series of 16 smokers who suffered from a primary psychiatric disorder, such as major depressive disorder (MDD), bipolar disorder (BPD), etc., and a truly co-morbid substance use disorder. All patients were in active outpatient substance abuse treatment protocols and were routinely seen in psychiatric care for medication management at the same facility. Patients were in different levels of recovery and suffering from differing amounts of active psychopathology. Patients who expressed an interest in smoking cessation during their usual course of treatment at the clinic were offered a trial of varenicline. All patients took varenicline in addition to their pre-existing psychopharmacology regimen. Patients had been treated for addiction to other substances but were not enroled in any specific psychotherapeutic smoking cessation protocol or counselling.
Methods
Charts were selected for historical review based upon the subjects attending a clinic (total population of approximately 300) that specialises in treating those with both psychiatric and concomitant substance use disorders. Naturalistically, patients were placed on varenicline for smoking cessation in the course of their usual treatment by their usual providers. After IRB approval, retrospectively, 16 consecutive charts with clear documentation of varenicline treatment for at least 12 weeks were identified and selected for review as a case series. These charts were analysed to determine patient demographics, psychiatric diagnoses, substance dependence diagnoses, varenicline dose and duration of treatment, the number of cigarettes used pre/post varenicline use and adverse effects. The patients were all enrolled in a counseling system for their primary SUDs, but not directly addressing smoking behaviours. All patients included received a course of varenicline as part of their treatment plan. This was dosed per regulatory guidelines in all cases. Clinical notes were available to confirm prescription variables. The primary outcome measure was self-reported smoking behaviour, as indicated by whether the patient quit smoking, reduced the number of daily cigarettes used, or neither. As this was not a prospective trial, the final outcome measurement was obtained at a certain time point in treatment (i.e. The date the chart review occurred). There was no prospective or retrospective comparison group and chart notes delineating subjective cigarette use were used to determine outcomes.
Results
The group consisted of seven men (43.7%) and nine women (56.3%) and had a mean age of 36 years. Thirteen patients were of Caucasian origin (81%) while two were of African American (12.5%) and one was of Hispanic origin (6.25%). The most common psychiatric diagnoses present in this group were major depressive disorders (75%) and anxiety disorders, which included generalised, post-traumatic and panic disorder (50%). The most common substance use diagnoses included cocaine dependence (68.75%), opioid dependence (62.5%), alcohol dependence (56.3%), cannabis dependence (31.25%) and benzodiazepine dependence (25%). Most patients had more than one substance dependence diagnosis and most were in differing stages of sobriety.
All 16 patients had during the past year unsuccessful attempts at smoking cessation by means of nicotine replacement and/or psychosocial treatment. Before beginning treatment with varenicline, patients were told to fill the varenicline prescription, set a quit date and start varenicline a week before from an initial dose of 0.5 mg, taken once a day on days 1 to 3, to 0.5 mg, taken twice a day on days 4 to 7. A target dose of 1 mg, taken twice a day, was continued after the quit date. All patients were given reassurance and education about the product's side effect profiles while no additional pharmacotherapy or psychosocial treatment aimed at smoking cessation was given.
The average length of treatment for all 16 patients was 106.3 days. The smokers used an average of 25 cigarettes per day prior to varenicline treatment. This was reduced to an average of eight cigarettes per day after varenicline treatment. Four patients completely quit smoking cigarettes (25% of treatment completers). In addition, five (31%) more patients were able to cut back cigarettes to one per day. The average reduction in cigarettes was 16 per day, or 64%. The Wilcoxon signed-rank test evaluating pre- and post-cigarette smoking quantities was significant at p = 0.008.
Some initial side effects were noted, but only one patient (irritability) discontinued varenicline treatment. The most common adverse effects noted were flatulence (18.75%), nausea (12.5%), insomnia (12.5%), headaches (6.25%), intention tremor (6.25%), weight gain (6.25%) and irritability (6.25%). The FDA warns the public of possible neuropsychiatric decompensation and suicidality with varenicline use; none of our patients reported suicidality or any self-harming behaviour during this period. No patient had any notable increase in their baseline psychiatric symptoms.
Discussion
As noted above, there is very little, if any, data addressing techniques to enhance smoking cessation in patients who have co-morbid multiple SUDs. There is even less data in this area for SUD patients with co-morbid psychiatric illnesses. This paper makes an initial attempt to examine smoking cessation in this clinically complicated population subgroup. The authors utilised a retrospective chart review and found a reasonable rate of smoking cessation in this small population of patients, who completed the recommended treatment course. The low discontinuation rates in this simple historical case series designed study observed also seem promising. Varenicline use was not associated with suicidality or self-harming behaviour in our small sample size study, an observation that has been reported in other studies as well (Tonstad, Davies, Flammer, Russ & Hughes, Reference Tonstad, Davies, Flammer, Russ and Hughe2010; Gunnell, Irvine, Wise, Davies & Martin, Reference Gunnell, Irvine, Wise, Davies and Martin2009). Use of varenicline seems preferable to continuation of smoking in light of these case observations. We feel this data, albeit retrospective and limited, lend to the evidence base that varenicline is an effective anti-smoking agent. It further suggests that smokers with severe co-morbid mental illness and SUD may actually benefit from a simple pharmacologic intervention.
This study has its limitations: it is a small, retrospective chart review and thus, statistical conclusions are limited in scope. These patients were enrolled at a SUD clinic and all were in different stages of post detoxification and rehabilitation therapies – individual or group. Likely our results were due to a combined effect of varenicline and psychotherapy. The authors suspect that even though smoking cessation classes and counselling were not offered, patients could have used previously learned addiction therapy techniques and applied them towards reducing cigarette use. It is unclear if patients without this type of treatment and addiction therapy support would have a comparable rate of smoking cessation. Better-controlled, prospective studies are needed to shed light on this issue in general and within this understudied, complex, co-morbid population group. This study had no placebo, no control arm or a comparison group to statistically analyse. Therefore all of our findings are naturalistic and subject to the usual biases.
Although all patients had co-morbid SUDs and MHDs, the authors observed reasonable clinical gains in a treatment as usual setting when varenicline was introduced as a smoking cessation agent. Discontinuation due to adverse drug reactions was low and there was no increased suicidality or psychiatric decompensation in these patients. Simple pharmacotherapy with varenicline, with or without psychosocial support, may be of benefit for nicotine dependence among patients with co-morbid SUDs and MHDs.
Acknowledgements
None.
Financial Support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Conflict of Interest
Authors report no conflict of interest regarding this unfunded study.
Ethical Standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
