Findings from a published double-blind, placebo-controlled, randomised clinical trial designed to assess the efficacy and safety of varenicline compared with placebo in patients with a history of MDD*
Results of a Pfizer-commissioned study published this month in Annals of Internal Medicine reveal that smokers with a past or present diagnosis of major depressive disorder (MDD)* taking varenicline had a significantly higher likelihood of quitting smoking (after 12 weeks and at 52 weeks) than those who were given a placebo.1 These efficacy results were consistent with previous varenicline pivotal clinical trials amongst general populations without psychiatric disorders.2,3
The study met both the primary and secondary endpoints, demonstrating that participants in the varenicline group had a higher likelihood of quitting smoking at the end of the treatment period (12 weeks; varenicline vs placebo: 35.9% vs 15.6%; p<0.0001) and at the end of the study (52 weeks; 20.3% vs 10.4% respectively; p=0.0011) than those in the placebo group.1
Varenicline was generally well tolerated by the study participants, with an adverse event profile similar to that observed in smokers without psychiatric disorders. Depression rating scales used did not reveal any clinically significant deterioration in mood or anxiety in either treatment arm, and the rate of psychiatric serious adverse events, including depression and suicidal ideation, was similar between the varenicline and placebo groups.1 The most commonly reported adverse events, occurring in at least 10 percent of subjects treated with varenicline, included: nausea (varenicline vs placebo, 27.0% vs 10.4%), headache (16.8% vs 11.2%), abnormal dreams (11.3% vs 8.2%), irritability (10.9% vs 8.2%) and insomnia (10.9% vs 4.8%).1
The findings from this clinical trial offer important information that contributes to a further understanding of the clinical profile of varenicline, and the results suggest that varenicline may be a suitable smoking cessation treatment for smokers with a history of MDD.1
Gay Sutherland, Honorary Consultant Clinical Psychologist at the Specialist Smokers’ Clinic, South London & Maudsley NHS Foundation Trust commented:
“In the last seven years, our clinic has successfully helped many smokers with a current or past diagnosis of depression to stop smoking with varenicline. These data have provided additional evidence which support our experience in every day clinical practice.”
Dr Berkeley Phillips, UK Medical Director of Pfizer commented:
“A significant number of smokers seeking treatment for smoking cessation have a history of depression. Studies have also shown that smokers with mental health problems are heavier and more dependent smokers than those in the general population. We are therefore delighted that varenicline was shown to be effective in this patient population, whilst having an adverse event profile similar to that observed in smokers without psychiatric disorders.”
Healthcare professionals giving smoking cessation advice are advised by the National Institute for Health and Clinical Excellence (NICE) not to favour one medication over another, but to choose with the patient the one that seems most likely to succeed (having considered contra-indications, potential for adverse events and patient past experience/preference).4 All three main therapies (varenicline, nicotine replacement therapy and bupropion) are approved as first line therapies by NICE.4
The regulatory labeling for varenicline in the EU has been revised to include this clinical trial data in patients with major depressive disorder. For further information on psychiatric adverse events and guidance for prescribers please consult the varenicline summary of product characteristics at www.medicines.org.uk/emc. Care should be taken with patients who have a history of psychiatric illness and patients should be advised accordingly. Pfizer continues to conduct studies of varenicline, including in patients with psychiatric disorders.
*A past or present diagnosis of MDD; without psychotic features; on stable antidepressant treatment for MDD (≥2 months) ((N=378, 72%)) and/or with a successfully treated episode of MDD in the past 2 years.
1. Anthenelli RM, et al. Varenicline Increases Smoking Cessation in Subjects with Depression: A Randomized. Placebo-Controlled Trial. Poster Presented at the 166th Annual Meeting American Psychiatric Association; May 18–22, 2013; San Francisco, CA, USA.
2. Gonzales D, 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;296:47–55. 3. Jorenby DE, 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. 4. National Institute for Health and Clinical Excellence. Smoking cessation services in primary care, pharmacies, local authorities and workplaces, particularly for manual working groups, pregnant women and hard to reach communities Public Health Guideline 10. London: NICE, 2008. www.nice.org.uk/nicemedia/pdf/ph010guidance.pdf (Accessed August 2013)