8 THE BROWN UNIVERSITY PSYCHOPHARMACOLOGY UPDATE APRIL 2006

New warning
for nimodipine
The FDA issued an alert and re-
quested that Bayer add a boxed warn-
ing to the labeling of the calcium-
channel blocker nimodipine (Nimo-
top) to warn about medication admin-
istration errors: Nimodipine is ap-
proved for oral administration to im-
prove neurological outcome after sub-
arachnoid hemorrhage. (It has also
been used to treat memory deficits in
AD.) When administered intravenous-
ly or parenterally, it can cause serious
adverse events, including death.
Black box recommended
for ADHD drugs
An FDA advisory committee has
recommended that drugs used to treat
attention-deficit hyperactivity disorder
(ADHD), both methylphenidates and
amphetamines, should carry a black
box warning about an increased risk
of sudden death and cardiovascular
problems in both children and adults.
The FDA has said it will weigh the rec-
ommendation and a second panel will
convene in March.
FDA
From the
CASE REPORTS
Neuroleptic malignant syndrome
and aripiprazole
Patient: Female, 23 y.o.
Medications: aripiprazole (Abilify), lorazepam (Ativan), bromocriptine (Parlodel)
A 23 y.o. female with methamphetamine dependence and cannabis use was admitted to
a psychiatric facility for a 2-week history of psychosis, including delusional thoughts and
auditory and visual hallucinations. She had no history of psychiatric illness. Within 3
days of treatment with aripiprazole 30 mg once daily and lorazepam 1 mg PRN for agi-
tation she had improved. She was discharged on aripiprazole 30 mg/day with a diagnosis
of psychotic disorder NOS.
Two weeks later the patient was admitted to the hospital with tremor in the extremi-
ties, mild muscle rigidity, psychomotor retardation, diaphoresis and altered mental status.
Her last dose of aripiprazole was the day before. Her creatine phosphokinase (CPK) was
high at 866 U/L (reference range, 0-250).
The patient was presumed to have neuroleptic malignant syndrome (NMS). Aripipra-
zole was discontinued. She received lorazepam 0.5 mg PRN Q6H and bromocriptine 2.5
mg/day for rigidity. On hospital day 2, her rigidity was decreased and CPK had declined
to 474 U/L, but she was still tremulous and disoriented. On day 4 she was started on a
scheduled dose of lorazepam 1 mg Q6H. Her CPK continued to drop and by day 8 was
74 U/L. However, she continued to have delusional thoughts and on day 8 was transferred
to a psychiatric facility.
The authors write, This case illustrates the challenges of diagnosis of NMS-spectrum
illness in patients using atypical antipsychotic agents.

Srephichit S, Sanchez R, Bourgeois J: Neuroleptic malignant syndrome and aripiprazole in an antipsychotic-
nave patient. J Clin Psychopharmacol 2006; 26(1): 94-95.
British NICE proposes limited use
of AD drugs
Based on cost-benefit analysis, Brit-
ains National Institute for Health and
Clinical Excellence (NICE) is recom-
mending that anticholinesterase drugs
should be used only in those patients with
Alzheimers Disease (AD) of moderate to
high severity (about 40% of the total) and
not in patients with a more mild form of
AD who may derive only minimal bene-
fits. Last year NICE suggested these drugs
were not worth their cost of roughly 1,000
pounds ($1,750) per year. NICEs chief
executive, Andrew Dillon, explains that
based on clinical trial data from the drug
makers, NICE has been able to identify
the right way to use these medicines.
[Reuters, 1/23/06]
New drug packaging format
The FDA has unveiled a new format
for prescription drug information, to be
applied in all package inserts, in an ef-
fort to manage the risk of medication use
and reduce medical errors. This first re-
vision in 25 years includes a Highlights
section to provide immediate access to
the most important information. The
FDAs Acting Commissioner, Andrew
von Eschenbach, M.D., hopes that the
new format will help physicians have
more meaningful conversations with
their patients about a drugs benefits and
risks. [www.fda.gov/cder]
Study suggests risk in first-
generation antipsychotics
The results of a study weighing the
risks of first generation antipsychotic
medications against the newer atypical an-
tipsychotics suggest that the older drugs
are just as risky for elderly users as newer
drugs, such as risperidone (Risperdal) and
olanzapine (Zyprexa). In April 2005, the
FDA required new labeling warning that
NEWS NOTES
the atypicals increased risk of premature
death in the elderly. According to John
Davis, M.D., who had no ties to the recent
study, This paper is important because it
corrects the mistaken perception I think
many physicians may have that the older
generation of drugs is safer when it comes
to the mortality risk. Researchers ana-
lyzed the medical records of over 22,000
men and women aged 65 and over. They
found that those who took standard doses
of the older medications, such as Haldol
(haloperidol) and Thorazine (chlorpro-
mazine), were 37 percent more likely to
die prematurely than those taking newer
drugs. It is still unclear why these drugs in-
crease the risk of premature death. [N Engl
J Med 2005; 353(22): 2335-2341]