Download laboratory and other testing for patients

Antipsychotic
Polypharmacy
Nose Bleeds with
Risperidone
NOVEMBER 2004 VOL 27 NO 11
LABORATORY AND OTHER TESTING FOR PATIENTS TAKING PSYCHOTROPIC MEDICATIONS
Psychopharmacology has become more complex over the past
decade or so, with many more medications available from
different pharmacologic classes. Boundaries between medication
classes and linkages between drug categories and psychiatric
diagnoses have become more ambiguous. The selection of drugs
for treating general medical illnesses has similarly expanded,
increasing the number of potential drug interactions,
particularly in an aging population.
It has been a long time since BTP reviewed the issue of
laboratory (and related) testing for patients taking psychiatric
medications. We attempt to do that here, but first offer several
qualifications. The text and tables are neither exhaustive nor
definitive, but rather an informed compilation of research-based
knowledge and clinical consensus.1-4 They represent guidelines to
be weighed by individual clinicians tailoring decisions to specific
cases. Moreover, the comments that follow pertain to usual
therapeutic dosing and drug plasma levels. Situations of overdose
and toxicity require different thinking and concerns and,
therefore, different laboratory tests.
The standard medical approach begins with diagnosis.
Diagnosis, in turn, starts with a history (ideally through multiple
sources), proceeds through examination, and then moves to
indicated laboratory and other testing. An initial psychiatric
examination (including a medical history and review of systems),
leading to a psychiatric diagnosis, requires a differential
diagnosis. Potential medical, neurological, toxic, and other
causes of psychiatric symptoms must be considered and
eliminated or dealt with. When coexisting medical conditions are
identified, the needs of these conditions may necessitate more
frequent monitoring of pertinent laboratory tests. All that follows
in this article presupposes the application of these principles in
the ordering and interpretation of appropriate diagnostic tests.
Even if a patient has had a thorough medical evaluation by a
primary care physician in the recent past, a psychiatrist must
bring a knowledgeable and skeptical eye to consider occult
conditions that sometimes masquerade as psychiatric disorders
and may have been overlooked previously.
As part of a comprehensive psychiatric evaluation and periodic
re-evaluation, the possibility of drug or alcohol abuse should be
assessed. Laboratory screening can form part of this consideration.
Some psychiatric disorders may result from toxic agents, which
© 2004 Gelenberg Consulting & Publishing, L.L.C.
might also be considered based on a history or physical signs.
Women of childbearing potential require specific consideration of
pregnancy. Based on menstrual status, a pregnancy test may be
required before starting psychiatric medicines.
The electrocardiogram (ECG) is often informative and is
noninvasive and relatively inexpensive. Many psychiatric
drugs—such as ziprasidone (Geodon), tricyclic antidepressants,
and lithium—affect cardiac electrical conduction and
repolarization, sometimes as a result of an interaction with other
medications. In addition, many individuals have asymptomatic
pre-existing cardiac problems, such as prolonged cardiac
conduction. Therefore, a pretreatment ECG and, if indicated,
periodic monitoring, might be necessary.
The accompanying tables group psychotropic medications in
standard categories. Under “mood stabilizers,” for example, we
have listed three, although the number of proposed mood
stabilizers and those approved by the US Food and Drug
Administration (FDA) is growing. (Some of the medications we
discuss are used “off-label” for treating psychiatric disorders. For
example, carbamazepine [Tegretol and others] is listed as a mood
stabilizer but is not FDA-approved for the treatment of bipolar
disorder.) Some mood stabilizers, such as lamotrigine (Lamictal),
do not require routine laboratory testing. However, plasma levels
of lamotrigine and other mood stabilizers may need to be
monitored during concomitant use with other antiepileptic
medications in case of pharmacokinetic interactions.
Oxcarbazepine (Trileptal) is a chemical congener of
carbamazepine but requires fewer routine laboratory tests.
Monitoring of serum sodium levels should be considered during
oxcarbazepine maintenance treatment, especially if the patient is
taking other drugs known to decrease serum sodium levels,
because of an elevated risk of the syndrome of inappropriate
secretion of antidiuretic hormone (SIADH). Although less likely
to increase metabolism and decrease levels of other drugs than
carbamazepine, oxcarbazepine can have this effect in some
patients, so plasma levels may need to be monitored.
With valproic acid (Depakote, Depakene), there might be an
increased risk of polycystic ovary syndrome in women of
childbearing potential.5 If the clinical history and physical
examination find obesity, hirsutism, or loss of menses, a serum
assay for androgens may be in order. In addition to the tests
Any unauthorized reproduction constitutes a violation of federal law.
listed in the table for valproic acid, the Physicians’ Desk Reference
recommends periodic monitoring of liver function tests since this
agent carries a low risk of inducing potentially severe hepatic
cellular damage, particularly when multiple anticonvulsants are
combined in children.2 Other experts believe that periodic
monitoring is not necessary, but that liver function tests should
be performed when indicated by symptoms.6 For that matter,
there has emerged a clear divergence in the field between
common practice among neurologists and psychiatrists, who
tend not to obtain routine blood tests in patients treated with
valproic acid and carbamazepine, and more cautious
guidelines, such as the PDR. For purposes of completeness, we
have included the more cautious recommendations in our tables.
However, many knowledgeable, experienced, and thoughtful
clinicians employ laboratory tests less frequently.
Second-generation antipsychotics increasingly are being used,
singly or in combinations, for a growing list of psychiatric
indications, including mood stabilization. Currently, olanzapine
(Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and
zisprasidone have been approved by the FDA for mania, and
olanzapine has been approved also for long-term mood
stabilization in bipolar disorder. There is mounting concern over
the potential of second-generation antipsychotics to induce weight
gain and associated metabolic side effects, including
diabetes mellitus, hyperlipidemia, and hyperglycemia (BTP
2004;27:33–35). The table from the American Diabetes
Association consensus conference, adapted below, is minimalist.
Plasma lipids and glucose should probably be monitored more
frequently, particularly for older patients, or those with high (or
rising) body mass indices (BMIs) or other risk factors. Because of
special concerns about toxicity, clozapine is presented in its own
table. In addition to the tests listed for clozapine, a patient’s white
blood cell count and plasma level of troponin should be measured
if myocarditis is suspected.7 Clinicians should be aware of and
monitor regularly for symptoms of increased prolactin in patients
taking antipsychotics. If clinically indicated,* prolactin should
be measured, and if elevated, a work-up for the cause of the
elevation initiated.
Ziprasidone may prolong the QTc interval. A baseline ECG is
in order for patients taking ziprasidone or another antipsychotic
who have known heart disease, a history of syncope, a family
history of sudden death at an early age, congenital long QT
syndrome, or who are receiving other cardiac depressants.**
Subsequent ECGs are worthwhile if symptoms associated with a
prolonged QT interval (eg, syncope) occur.7 Patients taking
ziprasidone who are at risk for significant electrolyte disturbances
should have baseline serum potassium and magnesium assayed,
because hypokalemia or hypomagnesemia can increase the risk
© 2004 Gelenberg Consulting & Publishing, L.L.C.
42
of QT prolongation and arrhythmias, including torsades de
pointes. (Thankfully, there have been no reports of serious
arrhythmias in humans as a result of this.) Monitor serum
electrolytes periodically in patients for whom diuretic therapy is
introduced during ziprasidone treatment.
Animal studies have suggested that quetiapine may be
associated with the development of cataracts. Although there is
insufficient evidence that this association occurs in humans, the
product labeling recommends that patients treated with this
antipsychotic have a slit-lamp eye examination or a similarly
sensitive eye examination shortly after initiation of treatment and
at 6-month intervals.7 Clinicians should inquire about vision
changes in patients taking other antipsychotics and request
ocular evaluations once a year in patients over 40 years and once
every 2 years in those under 40 years. The PDR recommends
baseline and periodic eye examinations, including slit-lamp,
funduscopy, and tonometry, in patients taking carbamazepine,
because related drugs have been shown to cause eye changes.
Two antidepressants for which laboratory testing is required
are phenelzine (Nardil) and nefazodone (Serzone), both of which
call for repeated monitoring of liver function to minimize the risk
of hepatotoxicity. Tricyclic antidepressants can slow cardiac
conduction, which means a pretreatment ECG should be
considered (looking for pre-existing prolongation of conduction)
with follow-up as treatment is established. Even selective
serotonin reuptake inhibitors (SSRIs), generally relatively safe
medicines, can induce SIADH, especially in the elderly (BTP
1996;19:15–16). Once again, clinical observation and
considerations should lead to indicated laboratory tests; in this
case, confusion or other central nervous system side effects should
prompt consideration of determining serum sodium and urine
osmolality. Routine monitoring of serum sodium might be
considered in the elderly. Some patients gain weight with SSRIs
and, even more so, with mirtazapine (Remeron). When weight
gain occurs, weight should be monitored along with plasma lipids
and glucose. Agranulocytosis may occur with mirtazapine. A
complete blood count should be done if symptoms arise.
Venlafaxine (Effexor) can raise blood pressure in a dose-dependent
fashion. It is safest, therefore, to obtain baseline and periodic blood
pressure measurements when venlafaxine is prescribed. Postural
blood pressures should be considered if orthostatic symptoms arise
(eg, with monoamine oxidase inhibitors).
Among drugs used to treat dementia, only tacrine (Cognex)
requires laboratory testing: serum levels of hepatic enzymes
should be measured every 2 weeks for 16 weeks, then every 3
months thereafter.8
To end where we began, the laboratory remains an important
but secondary resource for modern psychiatric practice. It can
assist in screening and differential diagnosis and, in selected cases, be
useful for periodic monitoring of treatment. In some cases indicated
in the tables, therapeutic drug monitoring is worthwhile. The
laboratory never has been and still is not a substitute for up-to-date
clinical knowledge and an astute clinician’s thinking and judgment.
Some day that may change, but that day is not here yet.
*In women, symptoms of elevated prolactin are galactorrhea and changes in
menstruation or libido. In men, they include changes in libido and erectile and
ejaculatory dysfunction.
**This includes Class I antiarrhythmics such as quinidine, tricyclic antidepressants,
and certain low-potency phenothiazines, including thioridazine (Mellaril and
others) and mesoridazine (Serentil), and many other general medical agents.
Expert consensus panel for optimizing pharmacologic treatment of psychotic
disorders. Expert consensus guideline series. Optimizing pharmacologic
treatment of psychotic disorders. J Clin Psychiatry 2003;64(Suppl 12):2–97.
2
Physicians’ Desk Reference, 58th ed. Montvale, NJ, Thomson PDR, 2004.
3
Miller AL, Chiles JA, Chiles JK, Crismon ML, Rush AJ, Shon SP: The Texas
Medication Algorithm Project (TMAP) schizophrenia algorithms.
J Clin Psychiatry 1999;60:649–657.
1
Frances AJ, Kahn DA, Carpenter D, Docherty JP, Donovan SL: The expert
consensus guidelines for treating depression in bipolar disorder.
J Clin Psychiatry 1998;59(Suppl 4):73–79.
5
Joffe H, Cohen LS, Suppes T, McLaughlin WL, Adams JM, Molay FJ, Hall JE,
Sachs GS: Polycystic ovarian syndrome is associated with valproate use in
bipolar women. Poster presented at the 157th annual meeting of the American
Psychiatric Association, New York, May 1–6, 2004.
6
Bowden CL: Valproate, in Schatzberg AF, Nemeroff CB (eds) Textbook of
Pharmacology, 3rd ed. Washington, DC, American Psychiatric Publishing, 2004,
pp 567–580.
7
Marder SR, Essock SM, Miller AL, Buchanan RW, Casey DE, Davis JM, Kane JM,
Lieberman JA, Schooler NR, Covell N, Stroup S, Weissman EM, Wirshing DA,
Hall CS, Pogach L, Pi-Sunyer X, Bigger JT Jr, Friedman A, Kleinberg D,
Yevich SJ, Davis B, Shon S: Physical health monitoring of patients with
schizophrenia. Am J Psychiatry 2004;161:1334–1349.
8
Kawas CH: Clinical practice. Early Alzheimer’s disease. N Engl J Med
2003;349:1056–1063.
9
Schatzberg AF, DeBattista C: The Black Book of Psychotropic Dosing and Monitoring.
New York, MBL Communications, 2003.
10
Ketter TA, Wang PW, Post RM: Carbamazepine and oxcarbazepine, in Textbook
of Pharmacology, 3rd ed. Washington, DC, American Psychiatric Publishing,
2004, pp 581–606.
4
MOOD STABILIZERS9,10
Carbamazepine (Tegretol and others)
In addition to the tests listed in the following chart, elderly patients should be monitored for signs of liver or bone marrow failure.
Baseline
Pregnancy test*
Complete blood count
Liver function tests
Blood chemistries***
Urinalysis
Thyroid function tests
Serum plasma concentrations
X
X
X
X
X
X
2 Wks
Monthly
Quarterly
X
X
X**
X**
X
X
Annually
X
When symptoms arise
X
X
X
X
X
X
X
X
X
* In women of childbearing potential based on menstrual status.
** For 3 months.
*** Rule out hyponatremia.
Lithium
Baseline
Pregnancy test*
Complete blood count
Blood chemistries (including renal tests)**
ECG***
Urinalysis
Thyroid function tests
Serum plasma concentrations
Weight/BMI/Waist circumference
Weekly for 4 Wks
Monthly for 3 Mths
Quarterly
X
X
X
X
X
X
Annually
X
X
When symptoms arise
X
X
X
X
X
X
X
X
X
X
X
X
* In women of childbearing potential based on menstrual status.
** Check creatinine levels and if creatinine and symptoms warrant, creatinine clearances.
*** In patients 45 years or older or with preexisting cardiac disease.
Any unauthorized reproduction constitutes a violation of federal law.
43
Valproic Acid (Depakote, Depakene)
In addition to the tests listed in the following chart, elderly patients should be monitored for signs of liver or bone marrow failure. For a discussion of liver
function tests In patients taking valproic acid, please see the text.
Baseline
Pregnancy test*
Complete blood count**
Blood chemistries
Serum plasma concentrations
Prothrombin time
Weight/BMI/Waist circumference
Amylase
2 Wks
Monthly for 6 Mths
X
X
X
Quarterly
Every 6 Mths
X
X
Annually
X
X
X
X
X
X
X
X
X
X
X
When symptoms arise
X
X
X
* In women of childbearing potential based on menstrual status.
** Include differential and platelets.
SECOND-GENERATION ANTIPSYCHOTICS*
Baseline
Pregnancy test**
Personal/family history
Weight/BMI
Waist circumference
Blood pressure***
Fasting plasma glucose
Fasting lipid profile
X
X
X
X
X
X
X
4 Wks
8 Wks
12 Wks
Quarterly
X
X
X
X
Annually
X
X
X
X
X
X
X
X
* More frequent assessments may be warranted based on clinical status (eg, more frequent lipid and glucose assessment in the event of marked weight gain).
** In women of childbearing potential based on menstrual status.
*** Orthostatic in elderly.
Copyright © 2004 American Diabetes Association. From Diabetes Care, Vol. 27, 2004:596–601. Adapted with permission from The American Diabetes
Association.
Note: Second-generation antipsychotics include aripiprazole (Abilify), olanzapine, quetiapine, risperidone, and ziprasidone. The consensus statement notes that
there is less experience with aripiprazole and ziprasidone and that these medications appear to induce less weight gain.
Clozapine (Clozaril and others)
In addition to the tests listed in the table below, orthostatic blood pressure should be measured weekly until the dose is stable and then monthly in the elderly.
Weight/BMI
Waist circumference
White blood cell count
Neutrophil count
Fasting glucose
Fasting lipid panels
Serum plasma concentrations
Baseline
Wkly for
6 Mths
Every Other
Wk from 6
Mths on
X
X
X
X
X
X
X
X
X
X
X
X
1X or 2X
per year
Inadequate response
or adverse effects
X
X
X
X
© 2004 Gelenberg Consulting & Publishing, L.L.C.
44
I N
B R I E F
■
Patients with bipolar disorder are at high risk of suicidal
behavior: between 25% and 50% of bipolar patients attempt
suicide at least once during their lifetime and 8.6% to 18.9%
die from completed suicide. In a recent study, the clinical
characteristics of bipolar patients at risk of suicide were
identified. Based on semi-structured diagnostic interviews,
F. Slama and coauthors determined that bipolar patients with
an early age at onset, a high number of depressive episodes, a
history of antidepressant-induced mania, comorbid alcohol
abuse, and a family history of suicidal behavior constitute a
subgroup more at risk of suicidal behavior than other
bipolar patients (J Clin Psychiatry 2004;65:1035–1039).
■
Manufacturers’ wholesale prices for 197 brand-name
prescription drugs most frequently used by Americans
aged 50 years and older rose 3.4% during a 3-month
period ending March 31, 2004, compared with a 1.2% rate
of general inflation during the same time period
(http://research.aarp.org/health/ib69_drugprices.pdf). The
antidementia drug donepezil (Aricept) and the
anticonvulsant gabapentin (Neurontin), which were two of
the top 25 selling brand-name drugs in 2003, rose in price
by 4.5% and 6.4%, respectively, in the first quarter of 2004.
Looking at price increases among drugs by therapeutic
category, anticonvulsants rose by 5.6% and antipsychotics
by 4.5%. Prices for antidepressants did not increase in the
first quarter of 2004.
■
In a small, double-blind, randomized, placebo-controlled,
6-week trial, M. Poyurovsky and colleagues found that
adding famotidine (Pepcid and others) to olanzapine
(Zyprexa) treatment for patients with schizophrenia did not
prevent or attenuate weight gain (Eur Neuropsychopharmacol
2004;14:332–336). Subjects who had famotidine added to
olanzapine and those who received placebo showed similar
increases in body weight: 4.8 ± 3.2 kg (10.7 ± 7.1 lb) and
4.9 ± 1.6 kg (10.9 ± 3.6 lb), respectively. Four (57.1%) of the
seven patients in the olanzapine/famotidine group and three
(42.9%) of seven in the olanzapine/placebo group had
clinically significant weight gain (ie, at least 7% of their
initial body weight).
Heather S. Hopkins
© 2004 Gelenberg Consulting & Publishing, L.L.C.
45
ANTIPSYCHOTIC POLYPHARMACY
There are several treatment guidelines, consensus
statements, and recommended algorithms for the treatment of
schizophrenia and other psychotic disorders. None favors the
concomitant use of multiple antipsychotic agents. Most
recommend avoiding this practice. (For example, see our
coverage of the recent update in the Texas Medication Algorithm
Project [TMAP] schizophrenia algorithm [BTP 2004;27:31–32].)
But despite lack of evidence and attendant costs and risks, the
use of multiple antipsychotic medications simultaneously is
common. Suzuki and others observe that about 90% of
psychotic patients in Japan receive multiple conventional
(first-generation) antipsychotic agents.1 These investigators
employed a naturalistic method to test the efficacy of single-drug
treatment in patients with chronic schizophrenia.
Forty-four patients with schizophrenia, who had been
taking an average of three antipsychotics for more than 6
months, were enrolled in the study. Using dosage conversion
tables, the authors cross-titrated medications and switched
each patient to a single antipsychotic. Patients were evaluated
after 24 weeks of monotherapy.
Over half of the patients remained clinically stable. Just
under a quarter showed further improvement, while an
identical number deteriorated. Overall, global and social
functioning remained unchanged.
In an accompanying editorial, Stahl notes that the use of
multiple second-generation antipsychotics simultaneously
presents a funding problem for public agencies.2 There is little
evidence for combining antipsychotics—whether a
second-generation with a first-generation agent or two
second-generation agents. Stahl points out the risks of additive
adverse effects, such as dyslipidemia and diabetes.
Goff and Freudenreich estimate that combined antipsychotics
are prescribed to 15% to 30% of patients.3 They observe that
the most common combination now in the United States is an
evening dose of quetiapine (Seroquel) with a daytime dose of
a less-sedating second-generation antipsychotic. They also cite
an uncontrolled trial that found enhanced efficacy from adding
risperidone (Risperdal) to clozapine (Clozaril and others).4
Lim et al describe three inpatients who benefited from the
combination of aripiprazole (Abilify) and low-dose clozapine.5
The patients—a woman with schizoaffective disorder, a woman
with bipolar disorder, and a man with schizophrenia—had
clozapine, 150 to 200 mg/day, added to aripiprazole, 30 mg/day.
They showed benefits in both positive and negative symptoms
with low serum clozapine levels, whereas aripiprazole alone had
produced minimal improvement. These authors speculate that
Any unauthorized reproduction constitutes a violation of federal law.
GELENBERG CONSULTING
& PUBLISHING, L.L.C.
P.O. Box 42650
Tucson, Arizona 85733-2650
Editorial Advisory Committee:
Ross J. Baldessarini, M.D.
Joseph Biederman, M.D.
Rubin Bressler, M.D.
Andrew W. Brotman, M.D.
Ned Cassem, M.D.
Harold J. DeMonaco, M.S., R.Ph.
Susan R. Donaldson, M.D.
William E. Falk, M.D.
Samuel J. Keith, M.D.
Martin B. Keller, M.D.
John Racy, M.D.
Eric M. Reiman, M.D.
Jerrold F. Rosenbaum, M.D.
A. John Rush, M.D.
Alan F. Schatzberg, M.D.
Nina R. Schooler, Ph.D.
Michael E. Thase, M.D.
Joanne Doller Wojcik, R.N., M.S.
the benefit resulted from combining clozapine’s
effects with the stronger D 2 receptor antagonism of
aripiprazole.
Goff and Freudenreich urge adequate monotherapy
trials, including with clozapine, before clinicians
consider antipsychotic polypharmacy. Patients who
respond insufficiently to clozapine may benefit from
the addition of another antipsychotic with stronger
D2 antagonism. When a combination is employed, it
should be for a finite period (eg, 6 weeks), with careful
monitoring of adverse effects and tracking of target
symptoms and their hoped-for improvement. Absent
clear benefit from an expensive and potentially risky
combination, discontinue it.
Suzuki T, Uchida H, Tanaka KF, Nomura K, Takano H, Tanabe
A, Watanabe K, Yagi G, Kashima H: Revising polypharmacy to
a single antipsychotic regimen for patients with chronic
schizophrenia. Int J Neuropsychopharmacol 2004;7:133–142.
1
Stahl SM: Focus on antipsychotic polypharmacy:
Evidence-based prescribing or prescribing-based evidence?
Int J Neuropsychopharmacol 2004;7:113–116.
2
Goff DC, Fredenreich O: Focus on polypharmacy in
schizophrenia: Does anyone truly benefit?
Int J Neuropsychopharmacol 2004;7:109–111.
3
Henderson DC, Goff DC: Risperidone as an adjunct to
clozapine therapy in chronic schizophrenics. J Clin Psychiatry
1996;57:395–397.
4
Lim S, Pralea C, Schnitt J, Bowers MB, Cooper C: Possible increased
efficacy of low-dose clozapine when combined with aripiprazole,
letter to editor. J Clin Psychiatry 2004;65:1284–1285.
5
Assistant Editor: Heather S. Hopkins
Managing Editor: Amy Boynton
“Biological Therapies in
Psychiatry” (ISSN 1044-422X)
NOSE BLEEDS WITH RISPERIDONE
Copyright 2004 Gelenberg Consulting
& Publishing, L.L.C. Published monthly by
Gelenberg Consulting & Publishing, L.L.C.,
2320 E. Adams. Correspondence to: P.O.
Box 42650, Tucson, Arizona 85733-2650.
All rights reserved.
Authorization to photocopy items once only
solely for internal or personal use is granted
provided that the base fee of $5.00 per
copy plus $.05 per page is paid directly to
Copyright Clearance Center, 27 Congress
St, Salem, MA 01970. Multiple copies may
not be resold or distributed without written
permission of the publisher.
0199-2716/00 $5.00 + $.05.
Any unauthorized
reproduction constitutes
a violation of federal law.
Please address all editorial correspondence
to: Alan J. Gelenberg, M.D., Department of
Psychiatry, University of Arizona, Health
Sciences Center, Tucson, AZ 85724.
Telephone toll-free: 1-800-700-9589 or
520-572-2039. Annual subscription (print
and online): In U.S., $75.00 (Personal),
$110.00 (Institution); Canadian and
International, $87.00 (Personal), $123.00
(Institution). Online only subscriptions are
20% off the US rates and free to residents:
for details, go to www.btpnews.com.
Single copies available at $8.00 (U.S.).
Bulk rates available upon request.
Binders available at $10.00 each.
POSTMASTER: Send address changes to:
Biological Therapies in Psychiatry,
Gelenberg Consulting and Publishing, L.L.C.
P.O. Box 42650, Tucson, Arizona 85733-2650.
Disclaimer: This publication provides general
coverage of its subject area. It is sold with
the understanding that the authors and
publisher are not engaged in rendering medical
or other professional advice or services.
If medical or other expert advice is required,
a competent professional should be consulted.
The authors and publisher shall not be
responsible for any damages resulting from
any error, inaccuracy, or omission contained
in this publication.
Dr Gelenberg is on the Speakers’
Bureau for Wyeth, Cyberonics, and Pfizer.
He receives research/grant support from
Pfizer and Wyeth. He is a consultant for
Eli Lilly, Pfizer, Vela Pharmaceuticals,
Best Practice, Bristol-Myers Squibb,
Astra/Zeneca, Wyeth, GlaxoSmithKline,
Cyberonics, Roche, ZARS, Janssen, and
Express Scripts.
Two reports to a medication monitoring program
in New Zealand described epistaxis associated with
risperidone (Risperdal).1 A 57-year-old woman
developed intense nose bleeds and headaches
immediately after she started to take risperidone,
1 mg daily. She did not have hypertension and was
taking no other medications. After 4 days,
risperidone was discontinued, and the nose bleeds
stopped. A 42-year-old man also began having
spontaneous nose bleeds while he was taking
risperidone. Coagulation tests were normal.
Harrison-Woolrych and Clark report that the
international drug monitoring database of the World
Health Organization (WHO) contains an additional
54 reports of epistaxis with risperidone.1 In 37 cases,
data were sufficient to establish causality. In 22 of
these, the nose bleeds began within 3 weeks of
risperidone’s initiation. Twelve patients stopped
risperidone and in 10, nose bleeds disappeared.
When 3 of those 10 patients restarted the
medication, nose bleeds recurred in only 1, a
15-year-old boy.
Thrombocytopenia has been associated with
risperidone and was reported in 9 of the 37 WHO
cases of nose bleeds with risperidone. Another
possible explanation is risperidone’s antagonism at
the 5-HT2A receptor, which can reduce platelet
aggregation and vasoconstrictor release from platelets.
Sponsored by The University of Arizona College of Medicine at the Arizona Health
Sciences Center. After reading the Biological Therapies in Psychiatry newsletter,
the learner will be able to: 1. Discuss new psychiatric drugs, including side effects and
drug interactions. 2. Describe new information on older medications and new
biological treatments.
The University of Arizona College of Medicine at the Arizona Health Sciences Center is accredited by the
Accreditation Council for continuing medical education (CME) for physicians.
The US Physicians’ Desk Reference lists the incidence of
nose bleeds in premarketing studies of risperidone as
occurring at a frequency of 0.1% to 1.0%.2
Epistaxis is rarely a serious problem and often
goes unreported. Detecting a relationship between
an adverse effect and a drug requires an awareness
of the possibility.
Harrison-Woolrych M, Clark DWJ: Nose bleeds associated
with use of risperidone. Brit Med J 2004;328:1416.
2
Risperdal. Physicians’ Desk Reference, 58th ed. Montvale, NJ,
Thomson PDR, 2004, pp 1764–1768.
1
BTP Gift Subscriptions
Give a friend or colleague a gift subscription to
Biological Therapies in Psychiatry and receive 10% off
your own renewal or new subscription!*
Your gift recipient will receive 12 monthly print and
electronic issues of BTP, access to our online
searchable database, and a BTP binder for storing
up to 24 issues (a $10 value).
You know the benefits of reading BTP.
Why not share them?
Call 1-800-700-9589 to place your order today!
*Offer good for a one-time 10% discount on a new or renewal
subscription ordered at the same time as the gift subscription.
The University of Arizona College of Medicine at the Arizona Health Sciences Center
designates this educational activity for a maximum of 6.0 category one credits toward the AMA Physician’s
Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the
educational activity.
CME assessment questions will be provided with the December issue of the BTP newsletter each year. To
attain credit, you must answer 10 of 12 questions correctly, and return the answer sheet to the University of
Arizona CME office by March 31. The cost for this activity is $25.
Please visit our web site at www.btpnews.com.
46