Safety and Efficacy Study of Topiramate to Aid in Smoking Cessation
Condition: Smoking Cessation
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this research study is to determine if topiramate is safe and effective in the
      treatment of smoking cessation
    

Detailed description: 
      Cigarette smoking is a pernicious national and global public health problem.1, 2 Nearly 50
      million Americans smoke cigarettes despite widely publicized and acknowledged health warnings
      and restrictions on public smoking. Smoking has been branded as the most important
      preventable cause of all deaths in the United States (US), and 45% of smokers will die of
      tobacco related disorders.3, 4 Tobacco dependence is mediated, in part, by the reinforcing
      effects of nicotine.5 According to the US Public Health Service Clinical Practice Guideline,
      Treating Tobacco Use and Dependence, every patient attempting to stop smoking should be
      offered pharmacotherapy for smoking cessation.6 Pharmacological treatment strategies have
      included nicotine replacement therapy (NRT (nicotine formulations)), antagonist therapy
      (mecamylamine), therapies to make nicotine intake aversive (silver acetate), non-nicotine
      medications that mimic some of nicotine's neurophysiological effects (antidepressants), and
      medications to block craving and withdrawal symptoms (nicotine formulations, antidepressants,
      clonidine). A number of drug therapies for smoking cessation have demonstrated some efficacy
      in facilitating smoking cessation. These include NRT using a variety of nicotine formulations
      (e.g., pill, gum, patch, etc.);7-14 combined nicotine replacement and mecamylamine;15 the
      antidepressants, bupropion SR,16-19 nortriptyline,19-21 doxepin,22 and fluoxetine;23, 24 the
      alpha2 agonist, clonidine;25-27 and the anxiolytic, buspirone.28 Among these agents,
      first-line pharmacotherapies approved by the US Food and Drug Administration (FDA) that
      include bupropion SR and various NRT products have been found to approximately double
      long-term abstinence rates compared with placebo.29-31 However, roughly 7 to 8 out of 10
      individuals who use these medications do not achieve long-term abstinence. I n addition to
      the limitations of currently available treatments for smoking cessation, several other
      clinical factors complicate the treatment of nicotine dependence. First, patients with a
      history of major depressive disorder appear to have a lower likelihood of achieving sustained
      smoking abstinence and an increased risk of depressive symptom emergence than patients
      without a history of major depressive disorder.32-44 Second, the emergence of prominent mood
      symptoms associated with nicotine withdrawal (e.g., anxiety, dysphoric or depressed mood,
      insomnia, irritability, and restlessness) reduce the likelihood of abstinence.35, 37, 44
      Third, appetite increases and weight gain are also components of nicotine withdrawal and have
      negative health consequences.30, 45 Activation of the mesocorticolimbic dopamine (DA) system
      has been implicated in the reinforcing and dependence-producing effects of nicotine.46, 47
      However, attempts to ameliorate the symptoms of nicotine dependence/withdrawal using DA
      receptors as therapeutic targets has met with only modest success.48, 49 Recent studies in
      rodents suggest that glutamatergic activation of N-methyl-D-aspartate (NMDA) receptors within
      the ventral tegmentum (VT) may be needed for nicotine to stimulate dopamine release in the
      nucleus accumbens.50-52 These findings are consistent with the reduction of nicotine-induced
      increases in locomotor activity observed with microinfusion of ionotropic glutamate receptor
      antagonists.53, 54 Thus, agents that indirectly modulate dopaminergic neurotransmission in
      the mesocorticolimbic reward circuit via their effects on presynaptic glutamatergic inputs to
      these dopamine neurons offer promise as novel adjuvants in the treatment of nicotine
      addiction.
    

Intervention name(s): Topiramate; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Topiramate
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment