Antipsychotics and QT prolongation

OBJECTIVE: To evaluate literature relating to cardiac QT prolongation and the use of antipsychotic drugs. METHOD: Literature searches of EMBASE, Medline, PsychLIT were performed in December 2001 and reference sections of retrieved papers scrutinized for further relevant reports. RESULTS: The Cardiac QTc interval is difficult to measure precisely or accurately but appears to be a useful predictor of risk of dysrhythmia (specifically torsade de pointes) and sudden death. It is less clear that drug-induced QTc prolongation gives rise to similar risks but data are emerging, linking antipsychotic use to increased cardiac mortality. Many antipsychotics have been clearly associated with QTc prolongation. Methodological considerations arguably preclude assuming that any antipsychotic is free of the risk of QTc prolongation and dysrhythmia. CONCLUSION: Available data do not allow assessment of relative or absolute risk of dysrhythmia or sudden death engendered by antipsychotics but caution is advised. Risk of dysrhythmia can very probably be reduced by careful prescribing of antipsychotics in low doses in simple drug regimens which avoid metabolic interactions. Electrocardiographic monitoring may also help to reduce risk but review by specialist cardiologist may be necessary.     

Incidence,prescription patterns,and determinants of antipsychotic use in patients with Parkinson's disease

Empirical data regarding the choice of antipsychotics for the management of psychosis in patients with Parkinson's disease are limited. This study aimed to evaluate the incidence and prescribing patterns of antipsychotics and to determine the predictors associated with the prescribing of typical antipsychotics in patients with Parkinson's disease. This was a retrospective cohort study analyzing data from the National Health Insurance Research Database in Taiwan between January 1, 2000, and December 31, 2006, in which patients with Parkinson's disease (ICD‐9‐CM codes 332) initially receiving any antiparkinsonian drug (n = 2095) were followed up to evaluate the subsequent use of antipsychotics. Kaplan–Meier statistics and multiple logistic regression were employed to evaluate the cumulative probability of antipsychotic use and determinants of prescribing of typical antipsychotics, respectively. The cumulative probability of initiation of an antipsychotic within 6 years was found to be 51%, and the proportion of patients who began taking an atypical antipsychotic increased from 11.1% in 2001 to 36.1% in 2005. Physician specialty was found to be the most influential predictor of the prescribing of typical antipsychotics: physicians with an internal medicine specialty were 10.62 times more likely (95% confidence interval, 4.64–24.32) to prescribe typical antipsychotics than were neurologists. The use of antipsychotics in Parkinson's disease is common, and the use of typical antipsychotics dominates antipsychotic treatment. Particular attention needs to be paid to improving practice, including efforts that encourage primary care providers to have the appropriate choice of antipsychotics in patients with Parkinson's disease. © 2011 Movement Disorder Society     

Maintenance antipsychotic medication patterns in outpatient schizophrenia patients: a naturalistic cohort study

OBJECTIVE: Newer antipsychotics are increasingly used in schizophrenia maintenance. The UK change has been slow with little known on switching patterns. We aimed to investigate antipsychotic prescribing patterns in schizophrenia patients. METHOD: A naturalistic six-site cohort sample of 600 patients were interviewed by researchers at 6-monthly intervals for 2 years to record their clinical and social functioning; use of services and medication for the preceding 6 months was obtained by structured extraction from clinical case notes. RESULTS: Alterations in antipsychotic medication were frequent in this group, mainly during periods of inpatient care. Atypical prescribing increased steadily, though slowly, across the period. Polypharmacy was less than anticipated. CONCLUSION: Inpatient care remains the main forum for switching of antipsychotics. The UK maintains a slow shift to atypical antipsychotics.     

"Real world" atypical antipsychotic prescribing practices in public child and adolescent inpatient settings

This article examines the factors that influence antipsychotic use among youth treated in public inpatient facilities. By combining data from 11 focus groups, a survey of 43 researchers and clinicians, and a chart review of 100 closed patient charts, we investigated the interplay between physicians' and staff members' perceptions of problems related to antipsychotic prescribing, their beliefs concerning optimal approaches, their actual recorded prescribing behaviors, and the discrepancies between their beliefs and their recorded practices. We discovered that antipsychotics are prescribed broadly to treat a variety of conditions, including nonpsychotic disorders among children in public inpatient facilities. Despite overall expert consensus regarding "best practices," physicians described systemic obstacles that prevent the application of these practices, and our data confirmed that best practices are not always followed. Future research should be done with this patient population and should investigate the factors that influence antipsychotic use among inpatient youth.     

Pharmacological treatment of hospitalised schizophrenic patients in Belgium

Objective. The aim of the present study is two-fold: (1) evaluate to what degree antipsychotic prescribing patterns are in accordance with published treatment recommendations; (2) gain insight in factors determining guideline adherence or non-adherence. Method. The medication use at first assessment of 1215 psychotic in-patients, participating in a naturalistic prospective follow-up study, was registered. Results. In Belgium, use of novel antipsychotics is frequent (69.4%) in hospitalised schizophrenic patients. In the total sample 57.8% receive only one antipsychotic drug. The majority of patients are treated with drugs of only one antipsychotic drug group, either first-generation antipsychotics (FGA) (27.8%) or second-generation antipsychotics (SGA) (42.3%). Roughly one-quarter of patients combine different types of antipsychotic. Antipsychotic dosing is adequate for the majority of patients, but one-third receive a higher than recommended dose. The use of SGA is influenced by the patients’ age and duration of illness. Polypharmacy and the administration of high doses FGA are influenced by symptom severity and illness duration. No clear determinants of SGA overdosing were found. Conclusions. SGA are most frequently used for the treatment for schizophrenic psychosis. Polypharmacy and excessive dosing are still frequently observed and appear influenced by the patient's clinical condition and illness duration. Evidence-based guidelines have not been sufficiently implemented in daily clinical practice yet.     

Impact of a Mental Health Based Primary Care Program on Quality of Physical Health Care

We examine the impact of mental health based primary care on physical health treatment among community mental health center patients in New York State using propensity score adjusted difference in difference models. Outcomes are quality indicators related to outpatient medical visits, diabetes HbA1c monitoring, and metabolic monitoring of antipsychotic treatment. Results suggest the program improved metabolic monitoring for patients on antipsychotics in one of two waves, but did not impact other quality indicators. Ceiling effects may have limited program impacts. More structured clinical programs to may be required to achieve improvements in quality of physical health care for this population.     

After out-of-home mental health treatment: atypical antipsychotic medication use and the probability of returning to treatment

Florida Medicaid claims data were used to assess antipsychotic medication use among children after therapeutic out-of-home mental health treatment. Fifty percent of youth received antipsychotics after the treatment episode, but differences exist across age, gender, and racial groups. Utilization was higher among males and youth ages 6–12, while blacks were less likely to be prescribed antipsychotics than whites. Youth receiving antipsychotics were less likely to return to out-of-home treatment within 6 months. However, among youth receiving antipsychotic medications, a higher medication possession ratio was not associated with the likelihood of returning to treatment. Such patterns require further investigation to determine whether they indicate inadequate treatment for some youth.     

Metabolic monitoring for patients treated with antipsychotic medications.

OBJECTIVES: Metabolic side effects of antipsychotic treatment include weight gain, dyslipidemia and increased susceptibility to diabetes. Patients with schizophrenia have increased coronary heart disease mortality and reduced life expectancy. There is an urgent clinical need to monitor antipsychotic-treated patients for metabolic disturbance. Our objectives were to review published international monitoring guidelines, establish goals for metabolic monitoring, and make recommendations for practice. METHOD: We reviewed the major published consensus guidelines for metabolic monitoring of patients treated with antipsychotic medications and selectively reviewed practice guidelines for the management of diabetes, dyslipidemia, and hypertension. RESULTS: Patients with serious mental illness have markedly elevated rates of metabolic disturbance and limited access to general medical care. Monitoring, but not necessarily medical treatment of metabolic disorder, falls within the scope of psychiatric practice and should include screening for metabolic disturbance as well as tracking the effects of antipsychotic treatment. In addition, psychiatrists and psychiatric services should work toward facilitating patients' access to medical care. There is considerable consensus in the published guidelines. Areas of dissent include which patients to monitor, the utility of glucose tolerance testing, and the point at which to consider switching antipsychotics. CONCLUSION: We encourage clinicians to adopt a structured system for conducting and recording metabolic monitoring and to develop collaborations with family physicians, diabetes specialists, dieticians, and recreation therapists to facilitate appropriate medical care for antipsychotic-treated patients.     

Ethnicity and prescription patterns for haloperidol, risperidone, and olanzapine

OBJECTIVE: Patients with schizophrenia may respond better to second-generation antipsychotics than to older antipsychotics because of their superior efficacy and safety profiles. However, the reduced likelihood among ethnic minority groups of receiving newer antipsychotics may be associated with reduced medication adherence and health service use, potentially contributing to poor response rates. This study examined whether ethnicity helped predict whether patients with schizophrenia were given a first- or a second-generation antipsychotic, haloperidol versus risperidone or olanzapine, and what type of second-generation antipsychotic was prescribed, risperidone or olanzapine, when other factors were controlled for. METHODS: Texas Medicaid claims were analyzed for persons aged 21 to 65 years with a diagnosis of schizophrenia or schizoaffective disorder who started treatment with olanzapine (N=1875), risperidone (N=982), or haloperidol (N= 726) between January 1, 1997 and August 31, 1998. The association between antipsychotic prescribing patterns among African Americans, Mexican Americans, and whites was assessed by using logistic regression analysis. Covariates included other patient demographic characteristics, region, comorbid mental health conditions, and medication and health care resource use in the 12 months before antipsychotic initiation. RESULTS: The results of the first- versus second-generation antipsychotic analysis indicated that African Americans were significantly less likely than whites to receive risperidone or olanzapine. Although not statistically significant, the odds ratio indicated that Mexican Americans were also less likely to receive risperidone or olanzapine. Ethnicity was not associated with significant differences in the prescribing patterns of risperidone versus olanzapine. CONCLUSIONS: When other factors were controlled for, African Americans were significantly less likely to receive the newer antipsychotics. Among those who received the newer antipsychotics, ethnicity did not affect medication choice.     

Pharmacoepidemiology of Antipsychotic Use in Youth with ADHD: Trends and Clinical Implications

Although concern has been raised about antipsychotic prescribing to youth with attention-deficit/hyperactivity disorder (ADHD), the available database is limited to individual studies. Therefore, in order to provide a synthesis of prevalence and time trends, we conducted a systematic review and pooled analysis of pharmaco-epidemiologic data on antipsychotic use in ADHD youth. Of 1806 hits, 21 studies (N) were retained that reported analyzable data for three separate populations: 1) antipsychotic-treated youth (N?=?15, n?=?341,586); 2) ADHD youth (N?=?9, n?=?6,192,368), and 3) general population youth (N?=?5, n?=?14,284,916). Altogether, 30.5?±?18.5 % of antipsychotic-treated youth had ADHD. In longitudinal studies, this percentage increased over time (1998–2007) from 21.7?±?7.1 % to 27.7?±?7.7 %, ratio?=?1.3?±?0.4. Furthermore, 11.5?±?17.5 % of ADHD youth received antipsychotics. In longitudinal studies, this percentage also increased (1998–2006) from 5.5?±?2.6 % to 11.4?±?6.7 %, ratio?=?2.1?±?0.6. Finally, 0.12?±?0.07 % of youth in the general population were diagnosed with ADHD and received antipsychotics. Again, in longitudinal studies, this percentage increased over time (1993–2007): 0.13?±?0.09 % to 0.44?±?0.49 %, ratio?=?3.1?±?2.2. Taken together, these data indicate that antipsychotics are used by a clinically relevant and increasing number of youth with ADHD. Reasons for and risk/benefit ratios of this practice with little evidence base require further investigation.     

Strategies for dosing and switching antipsychotics for optimal clinical management

Optimal clinical management of schizophrenia and bipolar disorder can be achieved through careful antipsychotic dosing and, if necessary, switching to another well-chosen antipsychotic using suitable switching strategies. For severely ill patients treated in clinical practice, adequate dosing may not result from following the relatively low dosing levels and abrupt titration schedules typically used in clinical registration trials. Data from recent effectiveness trials, naturalistic studies, and the Roadmap Expert Consensus Survey provide evidence of specific dose levels and titration schedules for antipsychotic agents that may be appropriate in clinical practice. Discontinuation and frequent switching of medication are common among patients treated with antipsychotics, but data suggest that an adequate trial of the first antipsychotic medication should be undertaken before switching to another antipsychotic medication. Making a decision to switch from a typical to an atypical antipsychotic or between atypical antipsychotics should involve consideration of variables relating to the patient, illness, medication, and the patient's environment. Switching can improve efficacy and tolerability but may also result in predictable side effects or withdrawal symptoms, including weight gain and metabolic effects as well as effects associated with prolactin changes. Many side effects that occur during switching are attributable to receptor profiles and antimuscarinic or antihistaminic blockade. Individualized switching strategies that include careful choice of medication, dose, and titration and tapering schedules; management of symptoms; and patient psychoeducation can reduce or treat side effects, increasing the likelihood of a successful switch and greater adherence and efficacy.     

Selective serotonin reuptake inhibitors and risk reduction for cardiovascular disease in patients with schizophrenia: A controversial but promising approach

Patients with schizophrenia (SCZ) are at high risk of cardiovascular disease (CVD) due to an inherited predisposition, a sedentary life style and the use of antipsychotic medications. Several approaches have been taken to minimize this risk but results continue to be unsatisfactory. A potential alternative is prescribing selective serotonin reuptake inhibitors (SSRIs). SSRIs decrease platelet aggregation and reduce the risk of coronary heart disease in patients with depression. We therefore aim to investigate whether there is evidence that supports the use of SSRIs to reduce the risk for CVD in SCZ. A review of the literature revealed five published reports relating to the impact of SSRIs on CV risk in SCZ. Three trials assessed the influence on metabolic parameters of fluvoxamine when combined with clozapine. Two of those studies found improvements with fluvoxamine. Of the other two reports, one indicates SSRIs as a group caused minimal but statistically significant increments in total cholesterol, low-density lipoprotein and triglyceride. The second report suggests that when SSRIs are combined with antipsychotics, the metabolic impact depends on the antipsychotic prescribed. While there are promising results, no conclusions can be made currently on whether SSRIs increase or decrease CV risk in SCZ. Further studies are needed to resolve this matter.     

Antipsychotic use in the treatment of outpatients with schizophrenia in the VA from fiscal years 1999 to 2006

OBJECTIVE: This study examined changes in prescribing patterns of antipsychotic medications to treat schizophrenia. METHODS: Pharmacy records for patients with schizophrenia were obtained from Department of Veterans Affairs databases. The proportion of patients prescribed specific second-generation antipsychotics or any first-generation antipsychotic was calculated per year. RESULTS: In fiscal year (FY) 2006, 78,849 veterans with schizophrenia were prescribed antipsychotic medication. For FY 1999 to FY 2006 the percentage of patients with schizophrenia who received first-generation antipsychotics decreased from 40.8% to 15.9%, but the percentage receiving olanzapine, after peaking at 32.0% in FY 2001, decreased to 19.0%. The percentage of patients given quetiapine increased from 2.5% to 18.8%; risperidone, from 25.5% to 29.7%. However, clozapine usage remained flat, at 2.0%-3.0%. Use of then-new ziprasidone and aripiprazole rose from 5.0% to 9.0%. CONCLUSIONS: Use of each antipsychotic newly marketed over eight years increased while use of risperidone was unchanged and use of olanzapine and the first-generation antipsychotics declined.     

Practical pharmacotherapy for acute schizophrenia patients

Well‐organized clinical guidelines of pharmacotherapy for schizophrenia are not necessarily applicable to emergency and acute‐phase situations. Thus, practical pharmacotherapy for acute schizophrenia patients should be based on data from real clinical practice and be independent of pharmaceutical companies. This study investigated the current guidelines being used to determine the initially preferred antipsychotics, durations required before an antipsychotic is viewed as being ineffective, and the strategies utilized for early non‐responders that include switching, high dose, and augmentation. In patients who develop side‐effects to the preferred antipsychotic drug, continued use may depend on the specific characteristics of the side‐effects. For acute‐phase patients, antipsychotics with high efficacy and effectiveness may be chosen based on meta‐analysis findings for not only double‐blinded but also rater‐blinded randomized controlled trials. Many previous studies have reported being able to make an early prediction at 2 weeks regarding the later response. These predictions were supported by the findings of a recent meta‐analysis of 34 studies that examined 9975 participants. In early non‐responders to the initial antipsychotic, the effectiveness of the switching strategy appears to depend on the initial antipsychotic administered and the antipsychotic the patient is subsequently switched to. Furthermore, the effectiveness of the strategy between switching and augmentation might also depend on the initial antipsychotic administered. The current findings might serve as the basis for the use of dosing above the licensed range versus continuing the use of conventional dosing in non‐responders, provided there is close monitoring of the side‐effects. Further research is required before any modifications of routine practices are undertaken regarding the direction of new potential treatments.