The drug is thought to work by binding to alpha-4, beta-2 nicotinic
acetylcholine receptors where it acts as a partial agonist. By partially
activating the nicotinic receptor complex, the intensity of a smoker's craving
for nicotine and withdrawal symptoms are both significantly reduced. Yet
because of the drug's binding, nicotine itself is blocked from binding to the
receptor, effectively diminishing a significant portion of the physiologic
effect (the reward) of nicotine, should the patient smoke after taking the
Efficacy was demonstrated in randomized, double-blind studies involving
more than 2,000 patients. On average, patients had smoked over two packs a day
for nearly 25 years. Twelve weeks of daily varenicline therapy increased the
odds of a patient's quitting smoking by nearly four times compared with
placebo and nearly twice the rate of smoking cessation of a control group
treated with oral bupropion.
The most frequent treatment-emergent adverse events during clinical trials
with varenicline were nausea, changes in dreaming, constipation, gas, and
The FDA ruled that the clinical trials data submitted supported the
efficacy and safety of the 5 mg and 10 mg immediate-release capsule versions
of the drug. However, the approvable action—short of full
approval—indicated the agency had at least some concern or question that
the company would need to address. Notably, with regard to the nonapprovable
action on the extended-release formulation, the agency indicated that it"
did not have an opportunity to review all of the information submitted
during the NDA review cycle." Federal law requires the agency to issue
at least a preliminary action within defined time periods on new drug
applications. The agency's action indicates reviewers simply ran out of time
before the deadline arrived as opposed to rejecting the extended-release
formulation due to significant concerns over efficacy or safety.
The immediate-release tablets were shown to be safe and effective in
patients with sleep-onset insomnia but did not benefit patients who wake
multiple times after falling asleep. The extended-release tablet is intended
to both shorten time to sleep onset and increase sleep duration.
Neurocrine Biosciences expressed disappointment over the split ruling but
emphasized that the company was "dedicated to working with the agency to
expedite response to the action letters."
Arch Gen Psychiatry 2006; 63:521-529
The most common side effects noted by those receiving haloperidol IV were
sedation and akathesia. Sixteen percent of patients rated the sedation and/or
akathesia as intolerable and declined the possibility of receiving open-label
treatment of their migraine pain with haloperidol.
Headache 2006; 46:781-787
Lilly submitted data from two randomized, double-blind clinical trials of
duloxetine in patients with GAD. A nine-week study of just under 500 patients
showed significant improvements in core anxiety symptoms such as anxious mood,
fears, and tension in 51 percent of patients taking 60 mg of duloxetine a day,
compared with 50 percent of patients taking 120 mg duloxetine a day and only
32 percent of patients blindly receiving placebo. Physical symptoms of pain
associated with anxiety were also significantly improved in those on
duloxetine (an average 41 percent reduction in pain in those taking 60 mg a
day and 37 percent reduction in those taking 120 mg a day) compared with
placebo (an average 16 percent reduction in pain). Duloxetine was also
associated with greater improvement in several quality-of-life measures.
The most common treatment-emergent adverse events associated with those
patients receiving duloxetine in the two trials were nausea, dizziness, dry
mouth, fatigue, hyperhidrosis, insomnia, constipation, diarrhea, decreased
libido, anorexia, somnolence, vomiting, and sedation.
The following medications appear in this edition of Med Check: