Medication Treatment for BPD: The Limited Evidence Base
Antipsychotics, especially olanzapine (Zyprexa), may be beneficial in treating borderline personality disorder, but the data are limited and mixed.
Chelation Therapy for Autism?
A study of chelation therapy for autism was stopped due to potential adverse effects.
Varenicline for Smoking Cessation
Varenicline (Chantix) should be used with caution in psychiatric patients attempting to quit smoking.
Minocycline for Schizophrenia: Preliminary Results
The results from an open-label study of minocycline (Solodyn and others) suggest benefit in the treatment of schizophrenia.
Modifying risk factors can help prevent dementia; Increased lighting improves cognition in elderly
Varenicline for Smoking Cessation
In recent decades, cigarette smoking among adults in the United States has declined. Nonetheless, an estimated 45 million people still smoke cigarettes, which strikingly increases mortality and illness.1 Rapidly absorbed when it is inhaled in smoke, which strengthens its reinforcing and addicting properties, nicotine binds to and produces conformational changes in nicotinic acetylcholine receptors in several different brain regions. When these receptors are stimulated, dopamine is released. Dopamine appears to mediate nicotine's reinforcing effects.
Varenicline (Chantix) competitively blocks nicotinic acetylcholine receptors and partially activates them. It causes some release of dopamine in the reward center and inhibits receptor binding by nicotine delivered from cigarettes. Thus, varenicline suppresses the symptoms of nicotine withdrawal and reduces the pharmacologic reward achieved by smoking cigarettes.
Clinical trials have shown varenicline to be superior to placebo and to sustained-release bupropion (Wellbutrin SR, Zyban, and others).1 In combined results from two comparison studies, the rates of abstinence from smoking at 12 weeks for varenicline, bupropion, and placebo were 50%, 36%, and 21%.2,3 Fifty-two weeks after the study was initiated and 9 months after it was discontinued, the 7-day point prevalence rates of abstinence from smoking were 29%, 23%, and 15%, respectively. Two open-label trials suggest short-term cessation rates are higher with varenicline than with nicotine replacement therapy.4,5
In a recent paper, Hays and Ebbert review varenicline and make suggestions for its clinical application.1 Candidates for varenicline should be motivated to quit smoking. The authors recommend establishing a target date to quit cigarettes 1 week after varenicline is initiated. Start varenicline with a 1-week dose adjustment period, beginning with 0.5 mg once daily on days 1-3, 0.5 mg bid on days 4-7, and a target dose of 1.0 mg bid on day 8, when smoking should stop. Some form of counseling should accompany the medication. Pregnant and lactating women should not take varenicline.
Nausea is common and may be attenuated when varenicline is taken with food. If nausea is particularly troublesome, the daily dose can be reduced to 1 mg, with renewed attempts to increase it to 1 mg bid. In patients with severe renal impairment, the target dose should be reduced to 0.5 mg daily. Varenicline does not induce or inhibit cytochrome P450 isoenzymes or inhibit renal transport proteins.6 Unexplained alterations in consciousness or visual disturbances have led to safety concerns about driving or operating aircraft or heavy machinery while taking varenicline.
Patients who have not achieved abstinence from smoking by 12 weeks and are not motivated to continue with the quitting plan should discontinue varenicline. If a patient has taken varenicline for 24 weeks or less, it may be stopped abruptly without tapering.
Insurance coverage for varenicline is highly variable. The retail cost of a 1-mg bid regimen is approximately three to four dollars per day.
Recent anecdotes of neuropsychiatric symptoms in patients taking varenicline—agitation, depression, suicidal ideation and behavior, worsening pre-existing psychiatric illness—have led the US Food and Drug Administration to add a warning to its label (BTP 2008;31:7). These symptoms can also occur in patients undergoing nicotine withdrawal and in others who continue to smoke, rendering the association with varenicline open to question. Smoking is common among psychiatric patients and may serve for many as a form of "self medication." Hays and Ebbert point out that varenicline was not tested in patients with psychiatric disorders and should be used cautiously in them.
Other approaches to smoking cessation include nicotine replacement and bupropion. Although it would make a priori sense to consider combining treatments, there are no studies to confirm the safety and efficacy of such combinations. Drug interaction studies found that combining varenicline with bupropion did not alter bupropion kinetics, and combining varenicline with transdermal nicotine did not alter nicotine kinetics but did cause more side effects, including nausea, and dropouts.7 Hays and Ebbert recommend against these combinations until their safety and efficacy have been established.
Tobacco use remains a common cause of morbidity and mortality. When people are motivated to quit, prescribers should knowledgeably discuss treatment options—including varenicline, bupropion, and nicotine replacement. In all cases, counseling should accompany medication for this purpose. The optimal length of continuing varenicline treatment has yet to be defined. Given the current concerns about adverse psychiatric effects, if it is to be prescribed to patients with psychiatric conditions, reactions should be monitored carefully. There is ongoing research with a nicotine vaccine, and it will be interesting to see how results turn out.
1Hays JT, Ebbert JO: Varenicline for tobacco dependence. N Engl J Med 2008;359:2018-2024.
2Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group: 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.
3Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group: Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47-55.
4Stapleton JA, Watson L, Spirling LI, Smith R, Milbrandt A, Ratcliffe M, Sutherland G: 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.
5Aubin HJ, Bobak A, Britton JR, Oncken C, Billing CB Jr, Gong J, William KE, Reeves KR: Varenicline versus transdermal nicotine patch for smoking cessation: Results from a randomised open-label trial. Thorax 2008;63:717-724.
6Tonstad S: Varenicline for smoking cessation. Expert Rev Neurother 2007;7:121-127.
7Pfizer Inc. Chantix™ (varenicline) tablets prescribing information. Available at http://www.chantix.com/content/Prescribing_Information.jsp. Accessed February 9, 2009.