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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