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Home , Antipsychotic, Aripiprazole, Atypical antipsychotic, Lurasidone, Olanzapine, Paliperidone

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Recommendations for lab monitoring of atypical

Kathryn Zeier, PharmD, Robert Connell, PharmD, BCPS, William Resch, DO, FAPA, and Christopher J. Thomas, PharmD, BCPS, BCPP, CGP

r. H, age 31, is admitted to an acute well established.2 Over time, these effects psychiatric unit with major depres- can lead to , poor car- Msive disorder, substance dependence, diovascular outcome, and type 2 , and generalized . In the past, mellitus. Each has its own risk pro- he was treated unsuccessfully with , file, but all atypical antipsychotics have , , , and lith- been shown to cause some metabolic ad- ium. The treatment team starts Mr. H on que- verse effects to a varying degree.3-5 A dose- tiapine, titrated to 150 mg at bedtime, to ad- effect relationship, if present, is estimated Vicki L. Ellingrod, dress suspected bipolar II disorder. to be small, and metabolic effects can oc- PharmD, FCCP At baseline, Mr. H is 68 inches tall and slightly cur at low dosages. and other Series Editor at 176 lbs ( [BMI] metabolic effects are seen most strikingly 26.8 kg/m2). The laboratory reports his glycat- in patients who are -naïve, 3,4,6 ed hemoglobin (HbA1c) at 5.4%; low-density and in children and adolescents. No lipoprotein (LDL), 60 mg/dL; total cholesterol, antipsychotic should be considered body 122 mg/dL; , 141 mg/dL; and high- density lipoprotein (HDL), 34 mg/dL. Within 1 month, Mr. H experiences a 16% in- Practice Points • All atypical antipsychotics carry a risk crease in body weight. HbA1c increases to 5.6%; LDL, to 93 mg/dL. These metabolic changes are of metabolic disturbance; and have the highest risk, followed not addressed, and he continues for by quetiapine and . another 5 months. At the end of 6 months, Mr. H weighs 223.8 lbs (BMI 34 kg/m2)—a 27% increase • Newer atypical antipsychotics may carry less of a risk of metabolic side effects, but from baseline. HbA is in the prediabetic range, 1c long-term data are lacking. at 5.9%, and LDL is 120 mg/dL.1 The treatment team discusses the risks of further metabolic • Obtain baseline and periodic monitoring of BMI, waist circumference, HbA , fasting effects, , and diabetes with 1c plasma glucose, and fasting . Mr. H. He agrees to a change in . • If you find an abnormality of any of these The association between atypical antipsy- parameters, consider one or more of the following: switching to an agent that is less chotics and metabolic adverse effects is risky; decreasing the dose or discontinuing Drs. Zeier and Connell are Second-Year Pharmacy Residents therapy; recommending diet and exercise; in Psychiatry, Dr. Resch is Director of Osteopathic Psychiatric Residency Program, and Dr. Thomas is Clinical Associate Professor and referring the patient to a program or of , Ohio University College of Osteopathic Medicine, clinician with expertise in the management Chillicothe Veterans Affairs Medical Center, Chillicothe, Ohio. of weight, diabetes, or lipids. Disclosure The authors report no financial relationships with any of the • Use monotherapy when appropriate to manufacturers mentioned in this article or with manufacturers of decrease the risk of side effects. Current Psychiatry competing products. Vol. 12, No. 9 51 Savvy Psychopharmacology

Table 1 Comparison of metabolic effects of atypical antipsychotics Drug Weight gain Dyslipidemia

Clozapine +++ +++ +++ Olanzapine +++ +++ +++ Risperidone ++ + + Quetiapine ++ ++ ++ +/0 +/0 +/0 +/0 +/0 +/0 Iloperidonea ++ +/0 +/0 + + + Clinical Point Asenapinea +/0 +/0 +/0 Clozapine and Lurasidonea +/0 +/0 +/0 olanzapine pose +++: significant; ++: intermediate; +: low; +/0: low or neutral aLimited data and/or long-term data are not available the highest risk Source: References 5,7 of weight gain; aripiprazole and ziprasidone present weight-neutral because all have the po- Newer atypical antipsychotics, such as the lowest risk tential for significant weight gain (>7% in , , paliperidone, and body weight).3,4 , seem to have a lower meta- An increase in weight is thought to be bolic risk profile, similar to those seen with associated with the actions of antipsychot- aripiprazole and ziprasidone.5 Patients 7 ics on H1 and 5-HT2c receptors. Clozapine enrolled in initial clinical trials might not and olanzapine pose the highest risk of be antipsychotic naïve, however, and may weight gain. Quetiapine and risperidone have been taking a high metabolic risk are considered of intermediate risk; aripip- antipsychotic. When these patients are razole and ziprasidone present the lowest switched to an antipsychotic that carries risk (Table 1).5,7 less of a metabolic risk, it might appear Patients taking an that they are experiencing a decrease in may experience an elevation of glu- metabolic adverse events. cose, serum , and LDL levels, and Metabolic data on newer atypical an- a decrease in the HDL level.2 These effects tipsychotics are limited; most have not may be seen without an increase in BMI, and been subject to long-term study. Routine should be considered a direct effect of the monitoring of metabolic side effects is rec- antipsychotic.5 Although the mechanism by ommended for all atypical antipsychotics, which dyslipidemia occurs is poorly under- regardless of risk profile. stood, an increase in the blood glucose level is thought to be, in part, mediated by antago- Recommended monitoring Discuss this article at nism of M3 muscarinic receptors on pancre- Because of the known metabolic side effects www.facebook.com/ atic β-cells.7 Clozapine and olanzapine pose that occur in patients taking an atypical an- CurrentPsychiatry the highest risk of dyslipidemia. Quetiapine tipsychotic, baseline and periodic monitor- and risperidone are considered of intermedi- ing is recommended (Table 2).2,10 BMI and ate risk; the risk associated with quetiapine waist circumference should be recorded at is closer to that of olanzpine.8,9 Aripiprazole baseline and tracked throughout treatment. and ziprasidone present a lower risk of dys- Ideally, obtain measurements monthly for Current Psychiatry 52 September 2013 lipidemia and glucose elevations.5 the first 3 months of therapy, or after any Savvy Psychopharmacology

Table 2 Recommended monitoring for a patient taking an atypical antipsychotic Parameter Baseline 1 Mo 2 Mo 3 Mo 6 Mo Annually Body mass indexa X X X X X X Waist circumference X X X X X X

b HbA1c X X X Fasting plasma glucose X X X Fasting panel X X X aEncourage patients to monitor their weight in addition to being weighed at the clinic bUnless patient develops diabetes mellitus, in which case American Diabetes Association guidelines for managing diabetes are recommended Source: References 2,10 Clinical Point Record BMI and waist circumference adjustments, then at 6 months, health care professional or to a program of patients taking and annually thereafter. Encourage patients with expertise in weight management also atypicals at to track their own weight. might be beneficial.2 Include family mem- baseline and track HbA and fasting plasma glucose lev- bers and significant others in the patient’s 1c them throughout els should be measured at baseline and education when possible. throughout the course of treatment. Obtain treatment another set of measurements at 3 months, Impaired fasting glucose. Encourage a then annually thereafter, unless the patient low-carbohydrate, high-protein diet with develops mellitus.2 high intake of vegetables. Patients should Obtaining a fasting lipid panel at base- obtain at least 30 minutes of physical ac- line and periodically throughout the tivity, five times a week. Referral to a dia- course of treatment is recommended. After betes self-management class also is appro- baseline measurement, another panel priate. Consider referral to a primary care should be taken at 3 months and annu- physician or a clinician with expertise in ally thereafter. Guidelines of the American diabetes.2 Diabetes Association recommend a fasting lipid panel every 5 years—however, good Impaired fasting lipids. Encourage your clinical practice dictates obtaining a lipid patients to adhere to a heart-healthy diet panel annually. that is low in saturated fats and to get ad- equate physical activity. Referral to a dieti- Managing metabolic side effects cian and primary care provider for medi- Assess whether the patient can benefit cal management of dyslipidemia might be from a lower dosage of current medica- appropriate.2 tion, switching to an antipsychotic with less of a risk of metabolic disturbance, or References 1. American Diabetes Association. Executive summary: standards from discontinuation of therapy. In most of medical care in diabetes—2010. Diabetes Care. 2010;33: cases, aim to use monotherapy because S4-S10. contributes to an increased 2. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, risk of side effects.10 and the North American Association for the Study of . Consensus development conference on antipsychotic and obesity and diabetes. Diabetes Care. 2004;27(2):596-601. Weight management. Recommend nutri- 3. Kahn RS, Fleischhacker WW, Boter H, et al; EUFEST study tion counseling and physical activity for all group. Effectiveness of antipsychotic drugs in first-episode and schizophreniform disorder: an open Current Psychiatry patients who are overweight. Referral to a randomised . Lancet. 2008;371(9618):1085-1097. Vol. 12, No. 9 53 continued Savvy Psychopharmacology

paliperidone in the treatment of schizophrenia and : a systematic review and exploratory meta-analysis. Related Resources CNS Drugs. 2012;26(9):733-759. • American Diabetes Association. Guide to living with e 6. D Hert M, Dobbelaere M, Sheridan EM, et al. Metabolic and diabetes. www.diabetes.org/living-with-diabetes. endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, • MOVE! Weight Management Program for Veterans. www. controlled trials and guidelines for clinical practice. Eur move.va.gov. Psychiatry. 2011;26(3):144-158. Drug Brand Names 7. Stahl SM. Stahl’s essential psychopharmacology, neuroscientific basis and practical applications. Oxford, : Aripiprazole • Abilify Olanzapine • Zyprexa Cambridge University Press; 2008. Asenapine • Saphris Paliperidone • Invega 8. Lieberman JA, Stroup TS, McEvoy JP, et al; Clinical Clonazepam • Klonopin Quetiapine • Seroquel Antipsychotic Trials of Intervention Effectiveness (CATIE) Clozapine • Clozaril Risperidone • Risperdal Investigators. Effectiveness of antipsychotic drugs in patients Fluoxetine • Prozac Sertraline • Zoloft with chronic schizophrenia. N Engl J Med. 2005;353(12): Iloperidone • Fanapt Venlafaxine • Effexor 1209-1223. • Eskalith, Lithobid Ziprasidone • Geodon 9. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of Clinical Point Lurasidone • Latuda second-generation antipsychotic during first-time usen i children and adolescents. JAMA. 2009;302(16):1765-1773. ADA guidelines 10. Gothefors D, Adolfsson R, Attvall S, et al; Swedish Psychiatric Association. Swedish clinical guidelines – prevention and recommend a fasting management of metabolic risk in patients with severe 4. Tarricone I, Ferrari Gozzi B, Serretti A, et al. Weight gain in psychiatric disorders. Nord J Psychiatry. 2010;64(5):294-302. lipid panel every antipsychotic-naive patients: a review and meta-analysis. 11. Schneiderhan ME, Batscha CL, Rosen C. Assessment of a Psychol Med. 2010;40(2):187-200. point-of-care metabolic risk screening program in outpatients 5 years; however, e 5. D Hert M, Yu W, Detraux J, et al. Body weight and metabolic receiving antipsychotic agents. Pharmacotherapy. 2009;29(8): good clinical practice adverse effects of asenapine, iloperidone, lurasidone and 975-987. dictates obtaining a lipid panel annually

Current Psychiatry 54 September 2013