© 2014 The Cochrane Collaboration. Background: There are at least three reasons to believe antidepressants might help in smoking cessation. Firstly, nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Secondly, nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Finally, some antidepressants may have a specific effect on neural pathways (e.g. inhibiting monoamine oxidase) or receptors (e.g. blockade of nicotinic-cholinergic receptors) underlying nicotine addiction. Objectives: The aim of this review is to assess the effect and safety of antidepressant medications to aid long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; lazabemide; moclobemide; nortriptyline; paroxetine; S-Adenosyl-L-Methionine (SAMe); selegiline; sertraline; St. John's wort; tryptophan; venlafaxine; and zimeledine. Search methods: We searched the Cochrane Tobacco Addiction Group Specialised Register which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, and other reviews and meeting abstracts, in July 2013. Selection criteria: We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow-up. Data collection and analysis: We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. Main results: Twenty-four new trials were identified since the 2009 update, bringing the total number of included trials to 90. There were 65 trials of bupropion and ten trials of nortriptyline, with the majority at low or unclear risk of bias. There was high quality evidence that, when used as the sole pharmacotherapy, bupropion significantly increased long-term cessation (44 trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to 1.76). There was moderate quality evidence, limited by a relatively small number of trials and participants, that nortriptyline also significantly increased long-term cessation when used as the sole pharmacotherapy (six trials, N = 975, RR 2.03, 95% CI 1.48 to 2.78). There is insufficient evidence that adding bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4 trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy (NRT) provides an additional long-term benefit. Based on a limited amount of data from direct comparisons, bupropion and nortriptyline appear to be equally effective and of similar efficacy to NRT (bupropion versus nortriptyline 3 trials, N = 417, RR 1.30, 95% CI 0.93 to 1.82; bupropion versus NRT 8 trials, N = 4096, RR 0.96, 95% CI 0.85 to 1.09; no direct comparisons between nortriptyline and NRT). Pooled results from four trials comparing bupropion to varenicline showed significantly lower quitting with bupropion than with varenicline (N = 1810, RR 0.68, 95% CI 0.56 to 0.83). Meta-analyses did not detect a significant increase in the rate of serious adverse events amongst participants taking bupropion, though the confidence interval only narrowly missed statistical significance (33 trials, N = 9631, RR 1.30, 95% CI 1.00 to 1.69). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Bupropion has been associated with suicide risk, but whether this is causal is unclear. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation. There was no evidence of a significant effect for selective serotonin reuptake inhibitors on their own (RR 0.93, 95% CI 0.71 to 1.22, N = 1594; 2 trials fluoxetine, 1 paroxetine, 1 sertraline) or as an adjunct to NRT (3 trials of fluoxetine, N = 466, RR 0.70, 95% CI 0.64 to 1.82). Significant effects were also not detected for monoamine oxidase inhibitors (RR 1.29, 95% CI 0.93 to 1.79, N = 827; 1 trial moclobemide, 5 selegiline), the atypical antidepressant venlafaxine (1 trial, N = 147, RR 1.22, 95% CI 0.64 to 2.32), the herbal therapy St John's wort (hypericum) (2 trials, N = 261, RR 0.81, 95% CI 0.26 to 2.53), or the dietary supplement SAMe (1 trial, N = 120, RR 0.70, 95% CI 0.24 to 2.07). Authors' conclusions: The antidepressants bupropion and nortriptyline aid long-term smoking cessation. Adverse events with either medication appear to rarely be serious or lead to stopping medication. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Evidence also suggests that bupropion is less effective than varenicline, but further research is needed to confirm this finding. Evidence suggests that neither selective serotonin reuptake inhibitors (e.g. fluoxetine) nor monoamine oxidase inhibitors aid cessation.

/pdf/antidepressants-for-smoking-cessation-1eio4jus21.pdf

Antidepressants for smoking cessation

Sleep abnormalities are associated with acute and chronic use of addictive substances. Although sleep complaints associated with use and abstinence from addictive substances are widely recognized, familiarity with the underlying sleep abnormalities is often lacking, despite evidence that these sleep abnormalities may be recalcitrant and impede good outcomes. Substantial research has now characterized the abnormalities associated with acute and chronic use of alcohol, cannabis, cocaine, and opiates. This review summarizes this research and discusses the clinical implications of sleep abnormalities in the treatment of substance use disorders.

/pdf/sleep-abnormalities-associated-with-alcohol-cannabis-cocaine-1a2dme54c7.pdf

Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use: a comprehensive review

Modeling withdrawal syndrome in zebrafish.

Mounting evidence implicates the zebrafish (Danio rerio) as a promising model species for reward and addiction research. Modeling drug abuse-related behavior in both adult and larval zebrafish produced a wealth of clinically translatable data, also demonstrating their sensitivity to various drugs of abuse and the ability to develop tolerance. Several studies have also applied withdrawal paradigms to model the adverse effects of drug abuse in zebrafish. In this review, we summarize recent findings of a wide spectrum of zebrafish drug abuse-related behavioral and physiological phenotypes, discuss the existing challenges, and outline potential future directions of research in this field.

Zebrafish models to study drug abuse-related phenotypes.

Impaired emotional-like behavior and serotonergic function during protracted abstinence from chronic morphine.

Objectives: The function of the Hypothalamic–Pituitary–Adrenal (HPA) axis during opioid dependence has been inconsistent. We compared HPA axis measures between subjects during methadone stabilization and drug-free detoxification with healthy controls. Methods: Sixty heroin dependent patients received either non-opiate treatment (NOT) with benzodiazepines and clonidine (n = 30) or methadone stabilization treatment (MT, n = 30), and their serum levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (COR) were measured and compared to those of healthy, nondependent controls. Results: Compared with healthy controls, CRH was significantly lower (p <. 001) while COR was higher (p <. 001) during acute withdrawal in the NOT group. CRH and COR was lower (p <. 001), while ACTH was normal in the MT group compared to healthy controls. Conclusions: Our findings suggest that chronic opioid dependence may cause reduced function of the HPA axis, while opioid withdrawal may decre...

Dysfunction of the hypothalamic-pituitary-adrenal axis in opioid dependent subjects: effects of acute and protracted abstinence.

The subjective and objective sleep patterns of patients with opioid dependence have been previously reported, but the sleep characteristics of patients in early methadone treatment, especially the objective sleep patterns, remain largely unexamined. This study was designed to explore the nocturnal sleep structure of patients on early methadone treatment. Twenty male methadone treatment (MT) patients and 20 male age- and body mass index-matched controls were assessed with overnight limited polysomnography. Subjective sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Compared with healthy controls, MT patients had lower sleep efficiency, shorter total sleep time, more awakenings and shorter slow wave sleep (SWS). The PSQI and ESS scores in MT patients were significantly higher than in the controls. ESS scores of the patients were significantly associated with the SWS. The findings indicate that patients in early MT have poor sleep quality and abnormal sleep architecture.

Nocturnal sleep architecture disturbances in early methadone treatment patients

INTRODUCTION Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a Chinese population. METHODS We enrolled 248 smokers in a hospital-based, randomized, smoking cessation trial conducted at four outpatient centers in Beijing. A total of 123 participants received an 8-week course of sustained-release bupropion (Bup-SR) and 125 participants received 8 weeks of placebo. All participants received brief education and counseling on smoking cessation. We determined rates of abstinence and smoking reduction based on chemical verification and self-report at 8 and 12 weeks. RESULTS At the end of the medication treatment (8 weeks) and at the end of the trial (12 weeks), the abstinence rates for Bup-SR were 29.3% and 39.8%, respectively, and 10.4% and 8.0% for placebo, respectively (both p < .001). Bup-SR was also superior to placebo in reducing cigarettes per day and urinary cotinine levels. CONCLUSION Bup-SR is efficacious for smoking cessation in healthy Chinese patients treated in the outpatient setting. It is well tolerated with a few mild side effects.

Sustained-release bupropion for smoking cessation in a Chinese sample: a double-blind, placebo-controlled, randomized trial.

The aim of the present study was to investigate the changes in the pituitary-thyroid axis (PTA) and the time course of the hormonal alterations in subjects with opioid dependence after abstinence. Blood samples from in-patients with opioid dependence and age- and sex-matched healthy controls were collected. The severity of opioid abuse and of withdrawal symptoms was assessed. Results were compared between patients with opioid dependence (n = 30) and healthy controls (n = 30). We found that free triiodothyronine and free thyroxine levels were comparable with healthy controls while thyroid-stimulating hormone (TSH) was lower in patients in acute opioid abstinence period. Also, TSH levels in patients remained lower than controls after 30 days of abstinence. These results indicate that PTA function is altered in opioid-dependent subjects. These data highlight the importance of screening the thyroid function for individuals with chronic opioid dependence.

Zuo-ning Jiang

Papers

Dysfunction of the hypothalamic-pituitary-adrenal axis in opioid dependent subjects: effects of acute and protracted abstinence.

Nocturnal sleep architecture disturbances in early methadone treatment patients

Sustained-release bupropion for smoking cessation in a Chinese sample: a double-blind, placebo-controlled, randomized trial.

Alterations in pituitary-thyroid axis function among opioid-dependent subjects after acute and protracted abstinence.