• In a randomized, double-blind, placebo-controlled study, nursing-home
residents with Alzheimer's disease saw no difference in psychotic symptoms
after taking either aripiprazole or placebo for 10 weeks. The
study, led by Joel Streim, M.D., a professor of geriatric psychiatry at the
University of Pennsylvania, was published in the July American Journal of
Geriatric Psychiatry. The study was supported by the makers of
aripiprazole, Bristol-Myers Squibb and Otsuka Pharmaceutical. A total of 131
Alzheimer's patients aged 59 to 96 were randomized to the aripiprazole group,
and 125 patients were randomized to the placebo group. Efficacy was evaluated
by changes from baseline on the Neuropsychiatric Inventory-Nursing Home
Version psychosis score and Clinical Global Impression severity score, and
these scores were not significantly different between the two groups after 10
weeks of treatment.
"A Randomized, Double-Blind, Placebo-Controlled Study of
Aripiprazole for the Treatment of Psychosis in Nursing Home Patients With
Alzheimer Disease" is posted at<http://ajgponline.org/cgi/content/full/16/7/537>.
•Xanomeline, a selective muscarinic receptor agonist under
investigation, shows promising effectiveness in a small study that was
published in AJP in Advance in July. Twenty patients with acute
exacerbation of schizophrenia or schizoaffective disorder were randomized in a
1:1 ratio to receive either xanomeline or placebo for four weeks in a
The xanomeline-treated patients had significantly greater symptomatic
improvement from baseline compared with placebo-treated patients. Improvement
was assessed by the Brief Psychiatric Rating Scale, the Positive and Negative
Syndrome Scale, and cognitive tests. The most common adverse events reported
more frequently in the xanomeline group than in the placebo group were nausea,
vomiting, gastrointestinal distress, salivation, diarrhea, constipation, and
The study was led by Anantha Shekhar, M.D., Ph.D., associate dean for
translational research, the Raymond E. Houk professor of psychiatry, and a
professor of pharmacology and neurobiology at Indiana University School of
Medicine, and colleagues and supported by Eli Lilly and Co.
"Selective Muscarinic Receptor Agonist Xanomeline as a Novel
Treatment Approach for Schizophrenia" is posted at<ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2008.06091591v1>.
• Pharmacotherapy for smoking cessation works, a meta-analysis published in
the July 15 Canadian Medical Association Journal concluded. Mark
Eisenberg, M.D., M.P.H., and colleagues pooled 69 randomized,
placebo-controlled, clinical trials of various drug therapies, which involved
nearly 33,000 participants. Varenicline, nicotine nasal spray,
bupropion, transdermal nicotine patch, nicotine tablet, and nicotine
gum were shown to be significantly more effective than placebo, with
an odds ratio of approximately 2. The efficacy results for inhaled nicotine
did not reach statistical significance. Varenicline was significantly more
efficacious than bupropion in a direct comparison of data from three trials of
varenicline that included a comparator bupropion group.
Varenicline has recently been linked to neuropsychiatric disturbances, such
as severe mood and behavior changes, vivid and strange dreams, and suicidal
ideation and behaviors. At the request of the Food and Drug Administration
(FDA), Pfizer has revised the drug's prescribing information and medication
guide to alert health care professionals and patients about these risks.
An abstract of "Pharmacotherapies for Smoking Cessation: A
Meta-Analysis of Randomized, Controlled Trials" is posted at<www.cmaj.ca/cgi/content/abstract/179/2/135>.
Prescribing information for varenicline is posted at<www.fda.gov/cder/foi/label/2008/021928s008lbl.pdf>.
•Dimebon, a drug being investigated for treatment of
Alzheimer's and Huntington's diseases, is more effective than placebo in
preventing cognitive-function decline in patients with mild-to-moderate
Alzheimer's, according to a randomized, double-blind, placebo-controlled
clinical trial published in the July 19 The Lancet. Cognition was
measured with the Alzheimer's Disease Assessment Scale-cognitive subscale
(ADAS-cog). The investigators, led by Rachelle Doody, M.D., Ph.D., of Baylor
College of Medicine, enrolled 183 patients with Mini-Mental State Examination
scores between 10 and 24 at 11 sites in Russia, including 89 patients who were
randomized to 60 mg/day dimebon and 94 who were given placebo. After 26 weeks,
the improvement from baseline was statistically significantly larger in the
dimebon group than the placebo group. Dry mouth and depressed mood were the
most frequently reported Adverse Events, both by 14 percent of patients. The
trial was funded by Medivation Inc.
An abstract of "Effect of Dimebon on Cognition, Activities of
Daily Living, Behaviour, and Global Function in Patients With Mild-to-Moderate
Alzheimer's Disease: A Randomised, Double-Blind, Placebo-Controlled
Study" is posted at<www.thelancet.com/journals/lancet/article/PIIS0140673608610740/abstract>.
• The package inserts for all antipsychotics, including but not limited to
quetiapine, ziprasidone, paliperidone, haloperidol, and
aripiprazole, have been modified with a new, standard
subsection on dystonia under "Adverse Reactions, Extrapyramidal
Symptoms." The warning states that "Symptoms of dystonia,
prolonged abnormal contractions of muscle groups, may occur in susceptible
individuals during the first few days of treatment." It warns that"
while these symptoms can occur at low doses, they occur more frequently
and with greater severity with high potency and at higher doses of
first-generation antipsychotic drugs. An elevated risk of acute dystonia is
observed in males and younger age groups." This labeling change took
effect for some of the drugs in April and others in May.
The announcement can be accessed at<www.fda.gov/medwatch/safety.htm>
by clicking on the April and May lists.
• The package inserts for antidepressants such as paroxetine,
sertraline, and fluvoxamine have been modified to
include standard wording about potentially important drug interactions with
warfarin and other drugs, such as aspirin and nonsteroidal anti-inflammatory
drugs, which may increase the risk of bleeding. The warning states that"
serotonin release by platelets plays an important role in
hemostasis" and "epidemiological studies.. .have demonstrated an
association between use of psychotropic drugs that interfere with serotonin
reuptake and the occurrence of upper gastrointestinal bleeding." The
label now specifically warns that "SSRIs and SNRIs ... may increase the
risk of bleeding events."
The announcement can be accessed at<www.fda.gov/medwatch/safety.htm>;
by clicking on the March and April lists.
• The prescribing information for atomoxetine has been
revised to include warnings about the drug's risks for adverse effects on
blood pressure and heart rate, urinary retention and hesitation in adults, and
potential interactions with drugs, such as the SSRI antidepressants, that
inhibit the cytochrome P450 isoenzyme 2D6. Cardiovascular adverse events from
new clinical trials in children, adolescents, and adults have been summarized
in the package insert.
The updated atomoxetine prescribing information is posted at<www.fda.gov/medwatch/SAFETY/2008/May_PI/Strattera_PI.pdf>.
• In June the FDA approved methylphenidate extended-release
tablets (Concerta) for treatment of attention-deficit/hyperactivity
disorder in adults aged 18 to 65, according to an announcement by
Ortho-McNeil-Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson. The
approved dosages range from 18 mg to 72 mg once daily.
• The FDA has approved a generic version of risperidone for
marketing in the United States. The generic risperidone tablets are
manufactured by Teva Pharmaceuticals, USA. The strengths of the tablets range
from 0.25 mg to 4 mg.
• The FDA will no longer issue "approvable" or "not
approvable" letters in response to drug companies' new drug
applications, the agency announced in july. Instead it will outline the
deficiencies of the application and recommendations to resolve them in a"
complete response" letter when an application is not approved.
Previously, the "approvable" and "not approvable"
letters implied a difference in the amount of revision or additional data
required by the agency for future approval. This change was made to"
help the FDA adopt a more consistent and neutral way of conveying
information" when an application is not approved, according to Janet
Woodcock, M.D., director of the FDA's Center for Drug Evaluation and Research.▪