• Zolpidem—extended release was approved by the
U.S. Food and Drug Administration (FDA) last month for the treatment of
insomnia. The non-narcotic, nonbenzodiazepine hypnotic is a longer-acting
version of zolpidem, which has been on the U.S. market since 1992. The new
two-layer formulation has an outer layer that dissolves quickly and a second
layer that dissolves slowly over several hours.
Like the immediate-release version, the new formulation will be a Schedule
IV controlled substance and is recommended for the short-term (seven to 10
days) treatment of insomnia.
In clinical trials, the extended-release formula was not only effective at
reducing time to sleep onset but also maintaining sleep throughout the night.
The most frequently observed side effects during clinical trials were
drowsiness, dizziness, and diarrhea.
Zolpidem—extended release will be available in a 12.5 mg tablet for
adults and a 6.25 mg tablet recommended for elderly patients.
• Health Canada ended distribution of thioridazine in
Canada as of September 30. Pharmacies can continue to dispense stock on hand,
giving patients some time to consult with their health care providers on
switching to another medication.
The regulator said the suspension of marketing approval was based on"
concerns about the use of the medication and rare occurrences of heart
rhythm changes that could be life threatening." Health Canada said that
information submitted by the manufacturer "has failed to demonstrate
that the benefits outweigh the risks" associated with the
• Pregabalin is significantly more efficacious than
placebo for the treatment of psychic and somatic symptoms of generalized
anxiety disorder and is well tolerated. A double-blind, placebo-controlled,
active comparator trial compared pregabalin at three dosages (300 mg/day, 450
mg/day, and 600 mg/day) with alprazolam (1.5 mg/day) and placebo in more than
450 patients for four weeks.
The Hamilton Anxiety Rating Scale scores of subjects in the three
pregabalin groups and the alprazolam group were statistically significantly
Both pregabalin and alprazolam were significantly associated with
somnolence and dizziness. In addition, pregabalin was significantly associated
with dry mouth, nausea, and blurred vision. The study was funded by
Arch Gen Psychiatry 2005; 62:1022-1030
• Ziprasidone and olanzapine have
similar long-term efficacy but differ significantly in their tolerability
profiles. A group of 126 patients from a six-week acute study of the two drugs
was followed for an additional six months under double-blind conditions. The
two drugs were associated with comparable improvements in patient scores on
the Brief Psychiatric Rating Scale and Clinical Global
Impression—Severity of Illness scale.
Compared with ziprasidone, olanzapine was associated with significant
increases in weight and body mass index, as well as increases in total
cholesterol, low-density lipoprotein cholesterol, and fasting insulin. Neither
drug was associated with significant increases in electrocardiogram QTc
intervals. The study was funded by Pfizer. Am J Psychiatry 2005;
• Neither risperidone nor olanzapine
was significantly better than placebo for the treatment of patients with
behavioral and psychotic symptoms of dementia (BPSD). A double-blind,
placebo-controlled comparator trial evaluated the two drugs in nearly 500
patients with moderate to severe BPSD over 10 weeks. Dosage was flexible,
ranging from 2.5 mg/day to 10 mg/day of olanzapine and 0.5 mg/day to 2 mg/day
of risperidone. Patients' BPSD were rated using the Neuropsychiatric Inventory
and the Clinical Global Impressions—Severity of Psychosis scale.
Subjects in all three treatment groups, including placebo, improved in most
measures of functioning with no statistically significant differences between
groups. Discontinuation of drug due to adverse effects was highest in the
olanzapine group at 16.2 percent, compared with 8.7 percent in the risperidone
group and 3.2 percent in the placebo group. Extrapyramidal symptoms were most
frequently observed in patients taking risperidone. Prolactin levels were
elevated in 78 percent of those taking risperidone compared with 16.7 percent
of those taking olanzapine and 5 percent of those taking placebo.
Weight gain was greatest in those taking olanzapine; however, there was no
statistical difference between the three groups for weight gain.
Eli Lilly and Co. funded the study. Am J Geriatr Psychiatry 2005;
• Atypical antipsychotics are just as likely as older,
typical antipsychotics to cause tardive dyskinesia and other movement
disorders, including parkinsonism, in elderly patients with dementia. Two
retrospective cohort studies followed nearly 22,000 elderly residents of
Ontario who had dementia and had recently been started on an antipsychotic
drug. Atypicals were prescribed to 9,790 patients, while 12,045 patients were
prescribed typical antipsychotics.
There was no statistically significant difference in the number of patients
who developed tardive dyskinesia on atypical drugs compared with typical
drugs. In addition, patients taking higher doses of the atypical drugs had
similar incidences of parkinsonism associated with medication therapy as
patients taking lower-potency typical drugs. However, those taking low to
moderate doses of atypical agents were 30 percent less likely to develop
parkinsonism. The study was funded by grants from the Canadian Institutes for
Arch Intern Med 2005; 165:1882-1888; J Am Geriatr Soc
• Modafanil is expected to receive final FDA approval
soon for the treatment of attention-deficit/hyperactivity disorder. The drug
will be jointly promoted by McNeil Consumer and Specialty Pharmaceuticals and
Cephalon Inc. More than 300 McNeil representatives who currently sell the
company's methylphenidate (extended release) will promote modafinil to
pediatric specialists, while about 400 Cephalon representatives will promote
the drug to psychiatrists, neurologists, and primary care physicians.
Modafinil is approved for the treatment of excessive sleepiness associated
with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift-work
sleep disorder. The most frequently observed adverse effects associated with
modafinil are headache, nausea, nervousness, stuffy nose, diarrhea, anxiety,
difficulty sleeping, and dizziness.▪