4 NEWS OCTOBER 2010 • CLINICAL PSYCHIATRY NEWS Smokeless Tobacco Deemed Harmful, Addictive

Products could pose increased health all of the smokeless tobacco Major Finding: Several meta-analyses indicate that smoke- products had nicotine concen- risks, American Heart Association warns. less tobacco use was associated with an increased risk of heart disease (relative risk 1.12,) and fatal stroke (RR 1.42 trations that were similar to cig- and RR 1.40). arettes with the highest con- BY LORINDA BULLOCK duced risk’ messages related to VITALS centrations (see chart). Data Source: Nonsystematic review of meta-analyses, ran- smokeless tobacco use on pub- Dr. Piano and her colleagues FROM CIRCULATION domized clinical trials, cohort or case control, and compara- lic perception, especially among tive studies regarding CV risk and ST product use primarily found that unlike the afore- mokeless tobacco products smokers who might be trying to conducted in Sweden and the United States. mentioned Swedish cohorts, are not safer alternatives quit,” Dr. Piano and her col- Disclosures: None was reported. there was no reduction in smok- Sto cigarette smoking, they leagues wrote. ing rates among people in the do not help smokers quit, and Citing “inadequate evidence United States using smokeless their long-term use can, in fact, of smoking cessation efficacy showed that tobacco chewers (milligrams per gram of tobac- tobacco. (The sale of smoke- increase the risk of fatal heart and safety,” the researchers had a significantly increased risk co), while chewing tobacco ap- less tobacco products such as attack, fatal stroke, and cancer, deemed as inappropriate the of first myocardial infarction pears to have “somewhat lower” moist snuff or snus is banned in the American Heart Association promotion of smokeless tobac- (odds ratio 2.23) compared with amounts compared with ciga- most of the European Union warned in a scientific statement. co as a way to reduce smoking- those who never used tobacco. rettes, Dr. Piano and her col- with the exception of Sweden The researchers, led by Mari- related diseases. Two other meta-analyses indi- leagues wrote. and Norway.) ann R. Piano, Ph.D., examined The American Heart Associ- cated that smokeless tobacco “Even though certain manu- In the United States about 8.1 several international studies to ation does recommend nicotine use was also associated with an facturing techniques are used million people are users of compare smokeless tobacco use replacement therapy (nicotine increased risk of fatal stroke (RR to reduce the level of these smokeless tobacco and its use is and its health risks. gum or a nicotine-releasing 1.42, n = 5 studies, and RR 1.40, compounds in some products, more prevalent in men than Meta-analysis data involving patch placed on the skin) as a n = 5 studies). they remain present in substan- women, and people between male, Swedish smokers for safer option for cigarette smok- The researchers explained tial concentrations in ST prod- the ages of 18-25 are the most 1976-2002 showed a significant ers wanting to quit. “Clinical that, like cigarettes, smokeless ucts, including Swedish snus,” likely to use smokeless tobacco, decrease in cigarette smoking studies have found no increased tobacco (ST) products still con- they said. the researchers wrote. that corresponded with an in- risk of heart attack or stroke tain nicotine of varying con- In a comparison of nicotine It also appears that although crease in use of smokeless to- with either type of nicotine re- centrations as well as a number concentration between three U.S. chewing tobacco use has bacco products, the investiga- placement therapy,” the AHA of carcinogens that are just as types of smokeless tobacco been on the decline since the tors wrote in the AHA journal, said in the written statement. harmful. products (chewing tobacco, dry 1980s, snuff consumption and Circulation. Despite the decline Metaanalysis data in the asso- Cigarettes and oral snuff have snuff, and moist snuff) and cig- production are increasing, the in cigarette use, concern is war- ciation’s scientific statement similar amounts of nicotine arettes sold in the United States, researchers said. ■ ranted, Dr. Piano, professor of http://circ.ahajournals.org/cgi biobehavioral science at the /reprint/CIR.0b013e3181f432c3 University of Illinois at Chica- indicated that smokeless tobac- Nicotine Concentrations in Smokeless Tobacco Products and go, explained: “Smokeless to- co use was associated with an Cigarettes Sold in the United States EWS bacco products are harmful and increased risk of heart disease Chewing tobacco* Dry snuff* Moist snuff* Cigarettes N addictive – that does not trans- (relative risk 1.12, n = 8 studies) (mean range) (mean range) (mean range) High Moderate Low late to a better alternative,” Dr. (Int. J Epidemiol. 2007;36:789- EDICAL Piano, said in a written state- 804). Nicotine 9.9 16.8 12.6 9.5-13.48.9-11.4 7.2-11.5 M (mg/g) (3.41-39.7) (10.5-24.8) (4.7-24.3)

ment released by the associa- Additionally, a subanalysis of LOBAL tion. INTERHEART (a study of *Smokeless products sold in Massachusetts in 2003 G “Scientists and policy makers 15,152 cases of first myocardial Source: Circulation LSEVIER need to assess the effect of ‘re- infarction in 52 countries) E Ketamine Infusion Relieves Bipolar Depression Quickly

BY ROBERT FINN with ketamine and experienced by at Major Finding: In patients with treatment-resistant bipolar depression, an in- least 10% of the patients were disassoci- FROM ARCHIVES OF GENERAL fusion of 0.5 mg/kg of ketamine significantly relieved depression within 40 PSYCHIATRY ation; feeling strange, weird, or bizarre; minutes, an effect that lasted at least 3 days. dry mouth; tachycardia; and increased single infusion of ketamine relieved Data Source: Randomized, placebo-controlled, double-blind, crossover study blood pressure. Abipolar depression within 40 min- VITALS involving 18 patients. Ketamine has been used in human and utes in patients with treatment-resistant Disclosures: The study was funded by the National Institute of Mental Health veterinary medicine since 1962, most bipolar disorder, according to a random- and by the National Alliance for Research on Schizophrenia and Depression. commonly for inducing and maintaining ized, placebo-controlled, double-blind A patent application for the use of ketamine for depression has been submit- general anesthesia, sedation in intensive crossover study involving 18 patients. ted, listing two of the investigators among the inventors; they have assigned care, analgesia, and treatment of bron- The effect lasted at least 3 days, wrote their rights on the patent to the U.S. government. chospasm. In the late 1990s, it increasingly Dr. Nancy Diazgranados and her col- became known as a drug of abuse and a leagues from the National Institute of mine or placebo. Two weeks later, the tistically significant improvements in de- date -rape drug. A previous study showed Mental Health. Patients in the study patients who had been given ketamine pression with ketamine, compared with that a single infusion of ketamine im- were an average of 48 years old, had suf- were given placebo and vice versa. Of placebo on all three scales beginning at proved suicidal ideation within 40 minutes fered from bipolar I or bipolar II depres- the 17 patients who completed the ket- 40 minutes after infusion and continuing (“Single Ketamine Injection Reduces Sui- sion for an average of 28 years, and had amine phase of the study, 12 (71%) re- for at least 3 days. Mean scores on the cidal Ideation,” November 2009, p. 13). failed an average of seven antidepressant sponded to ketamine. rating scales did not differ from placebo When used for general anesthesia, the treatments before the ketamine study. In contrast, of the 16 patients who on days 7, 10, and 14. initial dose of intravenous ketamine is Fifty-five percent of the participants had completed the placebo phase of the Within 40 minutes, 9 of 16 patients re- typically 1.5-4.5 mg/kg, substantially failed to respond to electroconvulsive study, only 1 (6%) responded to place- ceiving ketamine (56%) responded and an higher than the level used in this study. therapy. bo. additional 2 (13%) experienced complete Ketamine is thought to act as a non- Two-thirds of participants were on Investigators assessed the patients at remission of their depression. One day af- competitive inhibitor of the N-methyl-D- psychiatric disability, and all but one were baseline using several rating scales, in- ter the infusion, 44% of the patients had aspartate (NMDA) receptor, which is unemployed (Arch. Gen. Psychiatry cluding the Montgomery-Åsberg De- responded and 31% had remitted. part of the glutaminergic neurotrans- 2010;67:793-802). pression Rating Scale, the Hamilton None of the patients experienced se- mitter system. Several lines of evidence Patients were randomly assigned to re- Scale for Depression, and the Beck De- rious adverse events during the study. have implicated the glutaminergic sys- ceive an infusion of 0.5 mg/kg of keta- pression Inventory. Patients showed sta- Among the adverse events associated tem in bipolar disorder. ■