• Supplementation of vitamins B6, B12, and folic acid does
not significantly lower the risk of the emergence of depression in elderly men
with hypertension, according to a two-year study published online in the
Journal of Clinical Psychiatry on June 10.
A group of Australian men aged 75 years of age or older were randomly
assigned to take vitamin B supplement (n=149) or placebo (n=150) in a
double-blind manner; 118 in the vitamin B group and 123 men in the placebo
group completed two years of follow-up. All participants had hypertension, but
no depression, at baseline.
The emergence of depression symptoms, measured by change in the Beck
Depression Index (BDI) score from baseline, did not differ significantly
between the vitamin B-supplemented group and the placebo group. At the end of
two years, 84.3 percent of the men taking vitamin B supplements and 79.1
percent of those taking placebo remained free of clinically significant
depressive symptoms, and this difference was not statistically
An abstract of "Vitamins B12, B6, and Folic Acid for Onset of
Depressive Symptoms in Older Men: Results From a 2-Year Placebo-Controlled
Randomized Trial" is posted at<www.psychiatrist.com/abstracts/oap/ej07m03884.htm>.
• The combination of nortriptyline and
electroconvulsive therapy (ECT) is more effective than
nortriptyline alone as a long-term maintenance treatment of psychotic
depression in elderly patients who initially respond to acute ECT treatment,
according to a study conducted by researchers at the University of Barcelona
and Institut d'Investigaciones Biomediques Agusti Pi I Sunyer in Spain
published in the June American Journal of Geriatric Psychiatry.
Patients 60 years of age or older with a DSM-IV diagnosis of
severe, major depression with psychotic symptoms and a baseline score on the
Hamilton rating Scale for Depression of 21 or higher were first given acute
bilateral ECT three times a week until they reached remission or showed no
further improvement after three consecutive treatments. Patients who reached
remission were randomly assigned to receive a maintenance regimen with either
nortriptyline alone (n=17) or nortriptyline and ECT (n=16) for two years.
Thirteen patients in the nortriptyline monotherapy group completed the
study, including five without relapse or recurrence, two with relapse, and six
with recurrence during the study. Twelve patients in the combination therapy
group completed the study, including 11 who had no relapse or recurrence, and
only one who had relapse. Relapse was defined as the reemergence of depressive
symptoms within six months of the initial remission. Recurrence was defined as
a new episode of depression after at least six months of the initial
Statistical analyses showed that the combined nortriptyline and ECT
treatment was significantly more effective than monotherapy nortriptyline in
terms of time to relapse or recurrence. The authors reported that both groups
tolerated the treatment well.
The study personnel who evaluated patient outcomes and analyzed the data
were blinded to treatment assignment. The patients were not blinded. The
maintenance ECT was given weekly in the first month, every two weeks in the
second month, and monthly thereafter.
An abstract of "Continuation/Maintenance Treatment with
Nortriptyline Versus Combined Nortriptyline and ECT in Late-Life Psychotic
Depression: A Two-Year Randomized Study" is posted at<ajgponline.org/cgi/content/abstract/16/6/498>.
• Elan Corporation and Wyeth Pharmaceuticals released the results of a phase
2 clinical trial that showed a biologic agent known as
bapineuzumab to have some clinical activity in treating
patients with mild to moderate Alzheimer's disease. The randomized,
double-blind, placebo-controlled, multidose study enrolled approximately 240
patients and lasted 18 months.
Bapineuzumab did not reach statistically significant superiority over
placebo in all study participants. However, it beat placebo in certain
measures of clinical outcomes among patients who do not carry the
apolipoportein E4 (ApoE4) allele, suggesting a genetic factor in treatment
Bapineuzumab is a monoclonal antibody—a manufactured antibody that
attacks and reduces beta amyloid in the brain. Beta amyloid has long been
associated with the formation of plaques seen in the brain of Alzheimer
patients. The antibody is given through intravenous infusion. The two
companies said in a press release that they plan to continue the ongoing phase
3 development of this drug for Alzheimer's disease.
• In a phase 2, placebo-controlled clinical trial,
tarenflurbil has shown efficacy in slowing the neurological
decline in patients with Alzheimer's disease, according to a study published
in the June Lancet Neurology. Two hundred and ten patients with mild
Alzheimer's disease were randomized to receive either tarenflurbil or placebo
for a maximum of two years. Patients with mild disease (that is, a mini-mental
state examination [MMSE] score of 15 to 19) and taking tarenflurbil, 300 mg
twice daily, had slower decline in several outcome measures than those taking
placebo, but the drug was not more effective than placebo in patients with
moderate disease (that is, an MMSE score of 20 to 26).
Tarenflurbil reduces the production of the beta amyloid peptide Aβ42,
a molecule that has been suspected to contribute to the pathogenesis of
Alzheimer's disease. The study was sponsored by Myriad Pharmaceuticals, the
maker of the drug.
An abstract of "Efficacy and Safety of Tarenflurbil in Mild to
Moderate Alzheimer's Disease: A Randomised Phase II Trial" can be
accessed by going to<www.sciencedirect.com/science/journal/14744422>
and clicking on "Volume 7, Issue 6" in the left
• The FDA has approved quetiapine fumerate as an adjunct to
lithium or divalproex for the maintenance treatment of bipolar I disorder, the
manufacturer AstraZeneca announced in May. The approval was based on data from
two long-term clinical trials in adult bipolar I patients who were treated
with quetiapine for an average of 213 days. The primary endpoint was time to
recurrence of a depressive, manic, or mixed mood episode. Patients on
quetiapine, in addition to lithium or divalproex, had a significantly lower
risk of having a recurrent episode than those treated with placebo plus
lithium or divalproex.
Quetiapine has been previously approved for treating schizophrenia,
depressive episodes in bipolar disorder, and acute manic episodes in bipolar
The prescribing information of quetiapine is posted at<www1.astrazeneca-us.com/pi/Seroquel.pdf>.
• Aripiprazole has been approved by the FDA as a maintenance
treatment for manic and mixed episodes in bipolar I patients 10 to 17 years
old and for schizophrenia in adolescent patients 13 to 17 years old, the
manufacturers Otuska and Bristol-Myers Squibb announced in May. The indication
for pediatric bipolar disorder was derived from a four-week, randomized,
placebo-controlled clinical trial, and the schizophrenia indication in
adolescents was based on a six-week, randomized, placebo-controlled trial.
Approximately 200 participants were enrolled in each trial.
Aripiprazole was previously approved by the FDA for the acute treatment of
manic and mixed episodes in bipolar I patients 10 to 17 years old and the
acute treatment of schizophrenia in adolescents 13 to 17.
The prescribing information of aripiprazole is posted at<packageinserts.bms.com/pi/pi_abilify.pdf>.
• The Committee for Medicinal Products for Human Use (CHMP), the advisory
committee for the European Union's European Medicines Agency (EMEA), has
issued an opinion against the approval of ramelteon, a
sleeping aid manufactured by Takeda. Ramelteon has already been approved in
the United States to treat insomnia.
In a memo released on May 30, CHMP cited concerns about the company's
clinical trial data, which, CHMP believes, have not adequately demonstrated
the efficacy of ramelteon. They noted that ramelteon was significantly more
effective than placebo in only one outcome measure—sleep onset—in
only one of three studies, and the difference was considered too small to be
clinically relevant. Other aspects of insomnia were not significantly improved
by the drug compared with placebo. The Committee also noted a lack of evidence
for the long-term effectiveness of ramelteon.
Takeda has submitted a request to EMEA for the reexamination of the
negative opinion, according to a company announcement dated June 17.
• A United Kingdom court recently ruled in favor of the pharmaceutical
company in an ongoing legal battle over the government's decision to restrict
certain drugs for the treatment of Alzheimer's disease. The National Institute
for Health and Clinical Excellence (NICE) of England and Wales had released a
guideline that advised the National Health Services to limit the use of
cholinesterase inhibitors for treating patients with moderate but not mild
disease, because the drugs do not meet NICE's cost-effectiveness standard. The
Japanese company Eisai, which makes donepezil, has been
challenging the guideline in court. Last August, the company's argument that
drug cost should not be factored into national health-care decisions was
dismissed by a judge (Psychiatric News, September 7, 2007). This new
verdict agreed with Eisai's claim that NICE's cost-effective evaluation was
not made transparent by the organization. NICE said it would provide the
evaluation model to the company for comments and appeals.
NICE is an independent organization that compares and evaluates the
effectiveness of medical treatments and advises the National Health Services
on clinical decisions. ▪