Multiple Antipsychotic Medications Research Articles

ELECTROCONVULSIVE THERAPY FOR TREATMENT OF TACTILE HALLUCINATIONS

Abstract Tactile hallucinations can be highly distressing and lead to psychiatric morbidities and functional impairments. There are no established treatments for tactile hallucinations that occur outside of primary psychotic disorders, and available pharmacologic and nonpharmacologic therapies may have limited effectiveness. We present a case of a 75-year-old female with treatment-refractory tactile hallucinations successfully treated with electroconvulsive therapy (ECT). She endorsed 13 months of distressing tactile hallucinations described as slimly substances on her skin. Symptoms started insidiously, became more severe with time and refractory to multiple antipsychotic medications. She became so severely distressed from the tactile hallucinations that she developed a major depressive episode and became suicidal. Relevant medical history included one prior depressive episode, occipital lobe stroke, restless legs syndrome, and obstructive sleep apnea. She was hospitalized in an inpatient psychogeriatric unit and treated with ECT for 12 sessions over 3.5 weeks. Hallucinations responded well to ECT. Patient experienced some mild memory impairment from treatment. Treatment was optimized with duloxetine titration, addition of mirtazapine and repletion of B6 vitamin. Following the acute course of ECT, she reported an 80 % improvement in tactile hallucinations. Depressive symptoms improved, and suicidal thoughts resolved. She was able to discharge from the hospital and continued with maintenance ECT. Our case illustrates the potential therapeutic role of brain stimulation in the treatment of refractory cases of tactile hallucinations. Further studies are needed to determine effective treatment strategies for treatment-refractory tactile hallucinations to prevent progression to severe psychiatric disturbances and improve quality of life.

Study Finds Higher-Dose Antipsychotic Polypharmacy Does Not Increase Hospitalization

Study Finds Higher-Dose Antipsychotic Polypharmacy Does Not Increase Hospitalization

Trends in Results of HBIPS National Performance Measures and Association With Year of Adoption.

Multiple studies demonstrate a consistent pattern of improvement on quality measures among health care organizations after they begin collecting and reporting data. This study compared results on psychiatric performance measures among cohorts of hospitals with different characteristics that elected to begin reporting on the measures at various points in time. Quarterly reporting of Hospital-Based Inpatient Psychiatric Services (HBIPS) measures to the Joint Commission was used to examine trends in performance among four hospital cohorts that began reporting in 2009 (N=243), 2011 (N=139), 2014 (N=137), or 2015 (N=372). The HBIPS measures address admission screening, restraint and seclusion use, justification of use of multiple antipsychotic medications, and discharge planning. Comparisons were based upon initial quarters of data reported and change rates. After adjustment for covariates, the analyses showed that all cohorts significantly improved across quarters for admission screening, justification of multiple antipsychotic medications, and discharge planning. Restraint hours significantly dropped over the initial reporting periods, but only for the 2009 and 2015 cohorts. Seclusion hours significantly dropped over the six reporting periods for all cohorts except 2011. Several differences were observed across cohorts in the rate of change between baseline and final measurement for various measures. In nearly every case, however, hospitals that began reporting measurement data earlier performed better than subsequent cohorts during the later cohorts' first quarter of reporting.

Assessment of inpatient psychiatric readmission risk among patients discharged on an antipsychotic polypharmacy regimen: A retrospective cohort study.

Patients are frequently prescribed multiple antipsychotic medications, leading to higher healthcare costs and increased risk for side effects. The efficacy of multiple versus single antipsychotics to prevent acute relapse, measured by incidence of inpatient readmission, is investigated in Arizona, USA. A retrospective chart review compared socio-demographic and clinical data from 1,010 patients discharged on a single and 377 discharged on multiple antipsychotic medications. Case management records were reviewed for readmission within one year of discharge. Younger age, diagnosis of Schizophrenia or Schizoaffective Disorder, prescription of mood stabilizer, shorter length of stay, and discharge to residential treatment or crisis recovery unit were associated with multiple antipsychotics at discharge. Readmission rates of the single (13.7%) versus multiple (15.9%) antipsychotic groups were not statistically different (p=0.286). Logistic regression analysis established that only age (younger) and the prescription of a mood stabilizer at discharge were significant predictors for increased risk for readmission (p=0.010 and p=0.049, respectively). A Cox survival analysis supported these findings. Concomitant antipsychotic polypharmacy at discharge did not reduce readmission risk over a one-year period. Given the increased risk of side effects and financial costs of polypharmacy, this study did not provide evidence to support this practice. Strikingly, only two variables predicted readmission risk, younger age and prescription of mood stabilizer. Although practitioners should follow practice guidelines more closely to prevent unnecessary exposure to potentially lethal side effects of antipsychotic polypharmacy, further studies are needed to better identify patients at high risk for readmission.

Drug information update. Unconventional treatment strategies for schizophrenia: polypharmacy and heroic dosing.

The majority of patients respond to antipsychotic monotherapy at standard doses, but a subset of patients will require more heroic measures that include antipsychotic polypharmacy and high-dose monotherapy. Indeed, research has shown that roughly 30% of patients with psychosis are prescribed multiple antipsychotic medications. We discuss the potential benefits and challenges of these approaches and provide a rationale for why and when they should be utilised.

The effects of one community mental health center on antipsychotic polypharmacy: 12-months follow-up of patients with schizophrenia

Objective: Treatment with multiple antipsychotic medications (antipsychotic polypharmacy [APP]) in schizophrenia is recommended to be considered as a last resort, due to non-compliance, metabolic side effects and high mortality. On the other hand, in current clinical practice, APP is quite commonplace. The effects of one “community mental health center” (CMHC) activities on APP and clinical symptoms of enrolled schizophrenia patients were investigated in order to determine changes on antipsychotic treatment processes for schizophrenia. Methods: Sociodemographic Data Form, Positive and Negative Symptom Scale for Schizophrenia (PANSS) scores, Pharmacotherapy Compliance Scale evaluations and modes of medication utilization of 120 patients who were followed-up in this center for one year were evaluated retrospectively. Results: All PANSS subscale (positive, negative and general) scores of the patients decreased and compliance with drug treatment increased; rates of APP remained the same and mean drug treatment doses did not change. Conclusion: The insistence on APP, in spite of improvements in symptoms and patient compliance, shows the importance of maintaining community mental health activities as well as interventions targeting prescription habits of psychiatrists. Such interventions can provide a decrease in use of multiple medications. Results indicate the need to utilize community mental health center services to increase the effectiveness of psychopharmacotherapy for schizophrenia.

Multiple Antipsychotic Medication Use in Autism Spectrum Disorder.

The purpose of this study was to explore the use of multiple antipsychotic medications in patients with autism spectrum disorder (ASD) by reviewing the longitudinal medication management of 1100 patients consecutively treated for behavioral symptoms associated with ASD at a tertiary care specialty clinic. We identified all patients with ASD treated with daily doses of two or more antipsychotics for at least two visits at our clinic. For each patient meeting inclusion criteria, diagnostic and demographic data were collected. To evaluate clinical need and effectiveness of antipsychotic medications in this sample, we reviewed symptoms targeted with each antipsychotic medication and concomitant medications prescribed. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scale ratings had been completed at the time of each visit, and the duration of treatment with antipsychotic medications was determined. To evaluate the safety and tolerability of antipsychotic medication use in ASD, we reviewed reported adverse effects and calculated body mass index (BMI) change with treatment. Seventy patients met the inclusion criteria (6.4% of our sample). The majority of patients were moderately to severely ill Caucasian males, as determined by baseline mean CGI-S of 4.7 (SD = 0.8), and were diagnosed with autistic disorder and comorbid intellectual disability. The mean age was 15.1 years (SD = 10.9), the primary targeted symptoms were agitation/irritability, physical aggression, and self-injury. The majority of patients remained on two or more antipsychotics for >1 year. In this population, patients demonstrated greater symptomatic improvement and generally tolerated treatment without significant adverse effects. The use of two or more antipsychotic medications may be increasingly common in patients with ASD. This retrospective study demonstrates that this treatment approach may be of some clinical benefit, and is generally well tolerated. Prospective studies focusing on the efficacy and safety of concomitant antipsychotic medication usage in ASD should be considered.

A case of recurrent neuroleptic malignant syndrome.

SummaryNeuroleptic malignant syndrome (NMS) is a life-threatening neurologic complication associated with the use of neuroleptic agents and characterized by a distinctive clinical syndrome of fever, rigidity, autonomic nervous system dysfunction and mental status change. This report discusses the clinical presentation, possible etiology, pathogenesis and treatment of one case of recurrent NMS in a middle-aged woman with schizophrenia. NMS occurred after combined treatment with haloperidol and aripiprazole (the first episode) and, four years later, after combined treatment with haloperidol and clozapine (the second episode). This case highlights the need to be particularly cautious in the use of antipsychotic medications in patients with a history of NMS and, whenever possible, to avoid combined treatment with multiple antipsychotic medications in these patients.

Disentangling early sensory information processing deficits in schizophrenia

ObjectiveThe disentangling of early sensory information processing deficits and examination of their relationships to demographic and clinical factors are important steps for the validation of potential biomarkers and/or endophenotypes of schizophrenia. The aims of the present study were to characterize commonly used sensory event-related potential deficits, to determine whether they are (1) distinct from one another and (2) independently associated with important clinical characteristics. MethodsMMN, P3a and RON event-related potentials (ERP) were recorded from schizophrenia patients (SZ; n=429) and nonpsychiatric comparison subjects (NCS; n=286). Subgroup analyses on demographic and clinical variables were performed. ResultsSchizophrenia patients exhibited robust ERP deficits at frontocentral electrodes (MMN: d=1.10; P3a: d=0.87; RON: d=0.77), consistent with previous studies. Each ERP component uniquely accounted for variance in amplitude and schizophrenia deficits. Amplitude reductions occurred with increasing age in both NCS and SZ patients. A small subset of patients prescribed combinations of 1st and 2nd generation antipsychotics exhibited significantly reduced MMN amplitude relative to other medication-defined subgroups. ConclusionsMMN, P3a, and RON are dissociable deficits with distinct relationships to age and medication status in schizophrenia patients, potentially reflecting divergent pathophysiological processes. Reduced MMN in patients taking multiple antipsychotic medications appear to be attributable to greater severity of symptoms and functional impairments, rather than a medication effect. SignificanceIndependent information processing deficits in schizophrenia patients may differentially contribute to the commonly observed deficits in neurocognitive and psychosocial functioning.

Changes in Antipsychotic Medication Use after Implementation of a Medicaid Mental Health Carve-Out in the US

Many Medicaid programmes now offer behavioural healthcare through managed care organizations. Medicaid programmes are concerned about carve-outs because the use of non-included services may rise, limiting the efficiencies anticipated with the implementation of managed care. There also exist concerns that patients with serious mental illness may receive reduced care through managed care and consequently have poorer outcomes. This study examined prescription drug utilization among Medicaid recipients with the implementation of a mental health carve-out plan in Florida. In particular, this study examined short-run changes in the utilization of antipsychotic medications among individuals diagnosed with schizophrenia or episodic mood disorders with the implementation of Prepaid Mental Health Plans (PMHPs) in Florida Medicaid. This study used Medicaid data from 38 counties in Florida that implemented the PMHP programme in 2005 and 2006. The sample was limited to individuals aged≤64 years who were continuously enrolled in Medicaid. Individuals were required to have at least two diagnoses of schizophrenia, episodic mood disorders, delusional disorders or other nonorganic disorders (three-digit International Classification of Diseases, Ninth Revision [ICD-9] code of 295-298). Five different outcome measures were examined on a monthly basis for the 6 months pre- and post-PMHP implementation: penetration; adherence; Medicaid expenditures for antipsychotics; polypharmacy (multiple antipsychotic medications); and whether dosing was within guidelines. Generalized estimating equations were used to estimate associations between individual and insurance characteristics, and the outcome variables. The analyses were conducted using SAS procedure GENMOD. Empirical (robust) standard errors were calculated to account for repeated observations on the same individual. There were 153,720 monthly observations for the 12,810 people in the sample. Seventy-four percent of the sample was aged between 21 and 54 years, while 65% were female, 30% White, 14% Black and 44% Hispanic. The large proportion of Hispanics stems from the introduction of the PMHP programme in Dade County (Miami). The results indicate the implementation of the PMHP was associated with increased penetration, but reduced adherence, polypharmacy and expenditures by the Medicaid agency. There was no change in the likelihood of prescriptions being written within recommended dosage ranges. The introduction of the PMHP was associated with short-run changes in medication utilization among individuals with serious mental illness.

The Queensland Mental Health Clinical Collaborative and the Management of Schizophrenia

This paper describes the development of a collaborative group of mental health clinicians who have come together to improve practice in adult acute mental health settings for the inpatient management of schizophrenia. Sixteen acute adult mental health inpatient services across Queensland worked together to develop clinical indicators related to the inpatient treatment of schizophrenia. Data collection was conducted by using information available on existing databases and through statewide chart audits using scannable form technology. Through a secure intranet site, and statewide forums, clinicians were able to access information on clinical indicators enabling them to compare their site data to peer and state data. Available data from 15 of the 16 sites provided information on clinical indicators including average length of stay, 28-day readmission rates, antipsychotic prescribing, medication dose and the use of multiple antipsychotic medications at discharge. The formation of the Mental Health Clinical Collaborative has brought together clinicians across the State to develop clinical indicators and openly discuss ideas to inform and improve clinical practice. This process has been effective in improving the quality of routinely collected information across the State and in engaging clinicians in using health information to drive clinical practice.

Datapoints: Second-Generation Antipsychotic Medication Combinations for Schizophrenia

Combination pharmacotherapy for schizophrenia is reportedly increasingly common in the community (1). Yet efficacy of medication combinations for the treatment of schizophrenia and the frequency of such practices in different treatment settings remain largely unstudied. In addition, second-generation antipsychotics in combination pose an increased side-effect and risk burden at significant public and private cost. In order to determine patterns of prescribed second-generation antipsychotic combinations, we calculated frequencies using administrative and prescription data for over 6,000 individuals served by a large public mental health system for one month in 2002. Individuals were over the age of 18 and had a schizophrenia spectrum disorder. Seventy-six percent of individuals in the study (5,083 of 6,666 individuals) were given prescriptions for at least one second-generation antipsychotic medication. As shown in Figure 1, of the individuals who received a secondgeneration antipsychotic, many also received at least one other medication. Our study demonstrates how analysis of a large administrative database can improve knowledge of real-world psychopharmacological practices and enhance treatment improvement efforts. Despite the reported milder side-effect profile of second-generation antipsychotics, many patients received anticholinergic medications. This may reflect higher total dosages of antipsychotic medications, multiple antipsychotic medications, or overuse of anticholinergic medication (2). Other than for a brief period while a drug is being tapered, antipsychotic polypharmacy is inconsistent with current treatment guidelines, unsupported by rigorous research, and costly. This administrative database did not

Datapoints: Second-Generation Antipsychotic Medication Combinations for Schizophrenia

Back to table of contents Previous article Next article ColumnFull AccessDatapoints: Second-Generation Antipsychotic Medication Combinations for SchizophreniaCarol Eisen M.D., M.S.Roderick Shaner M.D.Jürgen Unützer M.D., M.P.H.Arlene Fink Ph.D.Kenneth B. Wells M.D., M.P.H.Carol Eisen M.D., M.S.Search for more papers by this authorRoderick Shaner M.D.Search for more papers by this authorJürgen Unützer M.D., M.P.H.Search for more papers by this authorArlene Fink Ph.D.Search for more papers by this authorKenneth B. Wells M.D., M.P.H.Search for more papers by this authorPublished Online:1 Mar 2008AboutSectionsView articlePDFView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View article Combination pharmacotherapy for schizophrenia is reportedly increasingly common in the community ( 1 ). Yet efficacy of medication combinations for the treatment of schizophrenia and the frequency of such practices in different treatment settings remain largely unstudied. In addition, second-generation antipsychotics in combination pose an increased side-effect and risk burden at significant public and private cost. In order to determine patterns of prescribed second-generation antipsychotic combinations, we calculated frequencies using administrative and prescription data for over 6,000 individuals served by a large public mental health system for one month in 2002. Individuals were over the age of 18 and had a schizophrenia spectrum disorder. Seventy-six percent of individuals in the study (5,083 of 6,666 individuals) were given prescriptions for at least one second-generation antipsychotic medication. As shown in Figure 1 , of the individuals who received a second-generation antipsychotic, many also received at least one other medication. Figure 1 Medications given in combination with a second-generation antipsychotic Our study demonstrates how analysis of a large administrative database can improve knowledge of real-world psychopharmacological practices and enhance treatment improvement efforts. Despite the reported milder side-effect profile of second-generation antipsychotics, many patients received anticholinergic medications. This may reflect higher total dosages of antipsychotic medications, multiple antipsychotic medications, or overuse of anticholinergic medication ( 2 ). Other than for a brief period while a drug is being tapered, antipsychotic polypharmacy is inconsistent with current treatment guidelines, unsupported by rigorous research, and costly. This administrative database did not allow verification of diagnoses with standardized instruments, and limited information about dosages and duration did not allow us to determine total dosage or whether polypharmacy was short or long term.Subsequent steps should include further research to explore efficacy and risks of medication combinations for treatment of schizophrenia and other alternative strategies to polypharmacy.Acknowledgments and disclosuresDr. Eisen and Dr. Wells were co-principal investigators on a study funded by Eli Lilly and Company. The other authors report no competing interests.Dr. Eisen is affiliated with the Department of Mental Health, Los Angeles County, and with the Semel Institute for Neuroscience and Human Behavior, Health Services Research Center, University of California, Los Angeles (UCLA), 10920 Wilshire Blvd., Suite 300, Los Angeles, CA 90024 (e-mail: [email protected] edu). Dr. Shaner is the medical director of Los Angeles County Department of Mental Health. Dr. Unützer is with the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle. Dr. Fink is with the Department of Medicine, UCLA. Dr. Wells is affiliated with the Semel Institute for Neuroscience and Human Behavior, Health Services Research Center, UCLA, and with RAND Corporation, Santa Monica. Harold Alan Pincus, M.D., and Amy M. Kilbourne, Ph.D., M.P.H., served as editors of this column.

Adverse events in children and adolescents treated with antipsychotic medications

To report the odds of developing adverse events associated with antipsychotic treatment among children and adolescents. A retrospective cohort design evaluating medical and pharmacy claims from one state Medicaid program was used to compare incidence rates for six categories of adverse events of antipsychotic use in 4140 children and adolescents newly prescribed one of six atypical or two conventional antipsychotic medications, January, 1998 to December, 2005 with prevalence rates of these conditions in a random sample of 4500 children not treated with psychotropic medications. The odds of developing obesity/excessive weight gain, Type II diabetes and dyslipidemia, digestive/urogenital problems, and neurological/sensory symptoms were higher for females and those prescribed multiple antipsychotic medications. The odds of developing cardiovascular conditions were higher for those prescribed multiple antipsychotic medications and haloperidol. The odds of developing somatic conditions were higher for females, children 12 and under, and those prescribed multiple antipsychotics. Those with lengthy exposure to antipsychotics were at higher risk of developing incident neurological/sensory symptoms. Those treated with concomitant antipsychotic agents were at higher risk of developing somatic problems, and digestive/urogenital conditions. Pediatric exposure to antipsychotic polypharmacotherapy confers a higher risk of developing adverse events than monotherapy, especially for females.

Letter

Back to table of contents Previous article Next article LetterFull AccessLetterJulie Kreyenbuhl Pharm.D., Ph.D.Marcia Valenstein M.D., M.S.John F. McCarthy Ph.D., M.P.H.Julie Kreyenbuhl Pharm.D., Ph.D.Search for more papers by this authorMarcia Valenstein M.D., M.S.Search for more papers by this authorJohn F. McCarthy Ph.D., M.P.H.Search for more papers by this authorPublished Online:1 Jul 2007https://doi.org/10.1176/ps.2007.58.7.1011aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail In Reply: We appreciate Dr. Babbar's letter, which brings much needed attention to a serious safety concern—hospitalization for adverse drug reactions, which could result from treatment with multiple antipsychotic medications. We share his concern about this and other potential adverse consequences of a treatment strategy that lacks solid evidence for its efficacy and safety. Dr. Babbar correctly notes that patients prescribed antipsychotic polypharmacy in our study were more likely to receive several other psychiatric medications, which could further increase their risks of adverse effects and subsequent hospitalizations. In addition, patients receiving polypharmacy were prescribed antipsychotic dosages that were the same as or higher than for those receiving monotherapy and had greater use of anti-Parkinson agents, which suggests that they were at risk of or were already experiencing side effects related to excess antipsychotic exposure. These findings lend further support to Dr. Babbar's hypothesis that rather than reflecting the severity of patients' psychotic symptoms (a potential indication for the use of polypharmacy), the higher rate of past-year psychiatric hospitalization was a result of the adverse effects of multiple medications. The overall goal of our study was to describe patient characteristics and treatment patterns associated with long-term antipsychotic polypharmacy. Although the safety and effectiveness of antipsychotic polypharmacy are important and unresolved issues, evaluating the outcomes of this treatment strategy was beyond the scope of our cross-sectional investigation. Further, we were not able to determine the reasons for the hospitalizations in question, although we do know that they reflected admissions to psychiatric or addiction treatment units. It is also important to note that the psychiatric hospitalizations occurred in the year before the period during which we documented patients' antipsychotic and other psychotropic treatments. We have no information regarding the medications prescribed before these admissions. This led us to infer that the previous hospitalizations were indicators of the severity of psychiatric illness of patients receiving antipsychotic polypharmacy, a conclusion reached by others who have reported a similar association between polypharmacy and previous hospitalization ( 1 , 2 , 3 ). Patients with refractory and disabling psychiatric symptoms (that may be reflected in increased use of inpatient psychiatric services) may be more likely to receive complicated psychotropic regimens that in turn induce adverse effects severe enough to result in hospitalization. We agree with Dr. Babbar that more research is needed to determine the extent to which this may be happening in routine clinical practice.

Adding or Switching Antipsychotic Medications in Treatment-Refractory Schizophrenia

This study compared patients with schizophrenia whose antipsychotic medications were switched to manage treatment-resistant positive psychotic symptoms with those for whom another antipsychotic was added. Psychiatrists' characteristics and perceptions of effectiveness of the medication change on clinical outcomes were also reported. Psychiatrists participating in a nationally representative mailed survey (N=209) reported on the clinical features, management, and response to the change in antipsychotic medication (added versus switched) of one adult patient with treatment-refractory schizophrenia under their care for at least one year. Thirty-three percent of patients were treated with an added antipsychotic medication. Compared with patients whose antipsychotic medications were switched, those with an added antipsychotic medication were more likely to be female, to have received care from the same psychiatrist for more than two years, and to have been recently prescribed an antidepressant. Compared with psychiatrists who switched antipsychotic prescriptions, those who added an antipsychotic reported that the change was less likely to reduce positive symptoms, improve functioning, and prevent hospitalization. Psychiatrists who added rather than switched antipsychotics reported more frequent attendance at educational programs sponsored by a pharmaceutical company. Consistent with other lines of research and practice guideline recommendations, psychiatrists perceive antipsychotic polypharmacy to be a generally ineffective strategy for treatment-resistant positive psychotic symptoms. In light of these findings, efforts to identify and implement more effective evidence-based pharmacologic approaches should be undertaken.

Adding or Switching Antipsychotic Medications in Treatment-Refractory Schizophrenia

Adding or Switching Antipsychotic Medications in Treatment-Refractory Schizophrenia

Using Pharmacy Data on Partial Adherence to Inform Clinical Care of Patients With Serious Mental Illness

Using Pharmacy Data on Partial Adherence to Inform Clinical Care of Patients With Serious Mental Illness

Impact of Splitting Risperidone Tablets on Medication Adherence and on Clinical Outcomes for Patients With Schizophrenia

Impact of Splitting Risperidone Tablets on Medication Adherence and on Clinical Outcomes for Patients With Schizophrenia

Prevalence, utilization patterns, and predictors of antipsychotic polypharmacy: experience in a multistate Medicaid Population, 1998–2003

Objectives: This study was conducted to estimate the prevalence of antipsychotic polypharmacy among fee-for service state Medicaid beneficiaries initiating antipsychotic drug therapy and to investigate psychiatric and demographic predictors of such polypharmacy. Methods: This was a retrospective cohort study employing Medicaid claims data from California, Nebraska, Oregon, Utah, and Wyoming for patients who filled >1 antipsychotic prescription between 1998 and 2003 and who were continuously eligible for benefits from 180 days before to 1 year after the index antipsychotic claim. Antipsychotic Polypharmacy was defined as initiation of multiple antipsychotic medications or at least 60 consecutive days of concomitant antipsychotic medication overlapping the index antipsychotic prescription at any time during the 365 days after the index drug claim. Primary and secondary diagnosis codes (International Classification of Diseases, Ninth Revision, Clinical Modification) were used to identify patients with mental disorders and mental health-related hospitalizations. Multivariate logistic regression, with adjustment for sex, age, race/ethnicity, state, mental health diagnoses, hospitalization, year, and type of index antipsychotic, was performed to identify predictors of polypharmacy. A multivariate Cox proportional hazards model was used to compare the cumulative incidence of polypharmacy by index antipsychotic drug. Results: The study cohort consisted of 55,481 individuals with ≥1 prescription claim for an antipsychotic drug. The mean prevalence of long-term antipsychotic polypharmacy in the year after initiating antipsychotic medication was 6.4%. Approximately half of those with polypharmacy were started on multiple antipsychotic drugs and half were started on monotherapy but received ≥2 antipsychotic drugs concomitantly in the year after drug initiation. Among the stronger predictors of polypharmacy were a diagnosis of schizophrenia (odds ratio [OR] = 2.95; 95% Cl, 2.43-3.58), recent mental health hospitalization (OR = 1.17; 95% Cl, 1.02-1.33), and the number of mental health diagnoses (OR = 1.07 per diagnosis; 95% CI, 1.06-1.08). Polypharmacy was more likely among male than female patients (OR = 1.26; 95% Cl, 114-1.39) and among those between the ages of 18 and 24 years. The cumulative incidence of polypharmacy was greater among patients initiating clozapine compared with those initiating other antipsychotics ( P < 0.001). Conclusions: In these fee-for-service Medicaid beneficiaries from 5 states, the prevalence of chronic antipsychotic polypharmacy was low in the year after the initiation of therapy. Polypharmacy was more common in patients with indicators of more severe mental illness.