Atypical antipsychotics in ordinary clinical practice: a pharmaco-epidemiologic survey in a south London service.

The introduction of atypical antipsychotics has triggered a reevaluation of treatment strategies in schizophrenia. Although research findings inform about the efficacy and safety of drugs, it is the decisions made daily in ordinary practice that affect the vast majority of patients. The aim of this paper was to examine the use of atypical antipsychotics in clinical care, by means of a survey of prescribing practices for clozapine, risperidone, olanzapine, sertindole and quetiapine for all patients treated for DSM-IV schizophrenia within a psychiatric service. Seventy-five (26%) of the 286 patients identified were on atypical antipsychotics. Patients on clozapine were mostly male, had more than 15 years of contact with psychiatric services and were poor responders. Patients prescribed other atypicals had responded to prior treatment with typical neuroleptics and had less than five years of contact with psychiatric services. Gender distribution was equal in this group. The use of research criteria for treatment resistance identified only one patient, as prolonged use of high-dose neuroleptics was uncommon. The new atypical antipsychotics appear to be replacing older neuroleptics as the first-line treatment of schizophrenia while clozapine is mostly reserved for poor responders. Clinicians' definition of treatment resistance was variable and below the threshold used in research.     

Forensic psychology: A guide to practice

Metabolic side-effects of atypical antipsychotics have led to concern about their relative safety compared with low doses of conventional neuroleptics. Akathisia is an often misdiagnosed side-effect, which leads to non-compliance and sometimes even exacerbation of psychosis or suicidal behaviour. In fact, little is known about the differences between antipsychotic drugs in clinical practice, since only as few as 20% of patients may be eligible for studies comparing antipsychotic medications with each other. The aim of this study was to find out if the use of conventional antipsychotics is associated with an increased risk of akathisia (compared with atypical antipsychotics) even when low doses of conventional antipsychotics are used. The Barnes Akathisia Rating Scale was used to evaluate akathisia in 100 outpatients on antipsychotic medication. Conventional antipsychotics were associated with an increased risk of akathisia compared with atypical antipsychotics, although the chlorpromazine equivalent doses of conventional antipsychotics were lower than those of the atypicals. An additional akathisia-provoking effect of SSRIs could not be ruled out. The results suggest favouring atypical antipsychotic medication in patients who may easily develop akathisia.     

On the relationship of atypical and low-dose conventional antipsychotics with akathisia in a clinical patient population

Metabolic side-effects of atypical antipsychotics have led to concern about their relative safety compared with low doses of conventional neuroleptics. Akathisia is an often misdiagnosed side-effect, which leads to non-compliance and sometimes even exacerbation of psychosis or suicidal behaviour. In fact, little is known about the differences between antipsychotic drugs in clinical practice, since only as few as 20% of patients may be eligible for studies comparing antipsychotic medications with each other. The aim of this study was to find out if the use of conventional antipsychotics is associated with an increased risk of akathisia (compared with atypical antipsychotics) even when low doses of conventional antipsychotics are used. The Barnes Akathisia Rating Scale was used to evaluate akathisia in 100 outpatients on antipsychotic medication. Conventional antipsychotics were associated with an increased risk of akathisia compared with atypical antipsychotics, although the chlorpromazine equivalent doses of conventional antipsychotics were lower than those of the atypicals. An additional akathisia-provoking effect of SSRIs could not be ruled out. The results suggest favouring atypical antipsychotic medication in patients who may easily develop akathisia.     

The effects of atypical antipsychotic medications on psychosocial outcomes

This review examines the question--Do atypical antipsychotic medications improve psychosocial outcomes?--by examining studies that compared the effects of atypicals to conventional antipsychotics or to other atypical medications. The authors reviewed randomized clinical trials of atypical antipsychotic medication that included psychosocial variables as outcomes. Findings from 31 published studies on more than 12,000 individuals generally showed that atypical medications led to significant improvements in negative symptoms compared to conventional antipsychotics. Effects on global assessment of psychosocial functioning and on the quality of life were mixed with only about half the studies reporting significant improvements. Olanzapine yielded the best results on psychosocial functioning; remoxipride was found to yield few significant changes on these variables. This review provides evidence that some atypical antipsychotics may have direct effects on some of the psychosocial disabilities that result from serious mental illness.     

Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes

This study compares the effects of atypical and conventional antipsychotic medications on treatment continuation and outcomes in a first admission sample of patients with schizophrenia treated in usual practice settings. In a sample of 189 participants with a research diagnosis of DSM-IV schizophrenia drawn from the Suffolk County Mental Health Project, we compared the effects of atypical and conventional agents on change of medication, medication gaps, and rehospitalization. For these analyses we used the method of survival analysis for recurrent events, in which the episodes of treatment rather than individual subjects are the units of analysis. In addition, we compared improvement in positive and negative symptoms from intake to 24- or 48-month followups for subjects who stayed on one type of medication or changed to atypicals from conventional antipsychotics. Atypical agents were associated with lower risk of medication change, medication gaps, and rehospitalization. Both conventional and atypical agents were associated with improvement of positive symptoms at followup, but only subjects on atypical agents at followup experienced a significant improvement in negative symptoms. We conclude that in usual practice settings, as in randomized clinical trials, atypical agents are associated with improved treatment continuation and outcomes.     

Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications

OBJECTIVE: Mortality rates in the year following new antipsychotic medication starts for neuropsychiatric symptoms of dementia were compared with rates after starts of other psychiatric medications. METHOD: The retrospective, cohort study used national data from the Department of Veterans Affairs (fiscal years 2001-2005) on patients older than 65 years who began outpatient treatment with psychiatric medication following a dementia diagnosis (N=10,615). Twelve-month mortality rates were compared in patients taking antipsychotics and those taking other psychiatric medications. The authors controlled for confounding by using multivariate models and propensity-scoring methods. Secondary analyses included a no-medication group and examination of mortality causes. RESULTS: All groups taking antipsychotics had significantly higher mortality rates (22.6%-29.1%) than patients taking nonantipsychotic medications (14.6%). Adjusted mortality risks for atypicals and for combined atypical and conventional antipsychotics were similar to those for conventional antipsychotics. The mortality risk was significantly lower for nonantipsychotic medications than conventional antipsychotics. Except for anticonvulsants, the adjusted risks for all individual classes of nonantipsychotics were significantly lower than the risk for antipsychotics. Mortality risks did not change over 12 months. The proportions of patients taking antipsychotics who died from cerebrovascular, cardiovascular, or infectious causes were not higher than rates for those taking nonantipsychotic psychiatric medications. CONCLUSIONS: Antipsychotic medications taken by patients with dementia were associated with higher mortality rates than were most other medications used for neuropsychiatric symptoms. The association between mortality and antipsychotics is not well understood and may be due to a direct medication effect or the pathophysiology underlying neuropsychiatric symptoms that prompt antipsychotic use.     

Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia

BACKGROUND: There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics. We are exploring whether this expanded clinical efficacy can also be seen in patients with treatment-resistant schizophrenia. METHOD: The subjects were 157 treatment-resistant inpatients diagnosed with DSM-IV schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week double-blind trial and rated with a standard measure of clinical antipsychotic efficacy (Positive and Negative Syndrome Scale [PANSS]). Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined. Data were gathered from June 1996 to December 1999. RESULTS: The underlying PANSS factor structure, as indicated by the factor loadings, was essentially identical at baseline and endpoint. At baseline, the excitement factor was followed by the positive, negative, cognitive, and depression/anxiety factors, explaining 49.4% of the total variance. At endpoint, the positive factor was followed by the negative, excitement, cognitive, and depression/anxiety factors, explaining 55.5% of the total variance. The endpoint data indicated statistically significant (p <.05) improvements over time on the positive factor for all 3 atypicals, but not for haloperidol. The negative factor showed significant improvement for clozapine and olanzapine, with significant worsening for haloperidol. Clozapine, olanzapine, and risperidone were superior to haloperidol on the negative factor, while clozapine was also superior to risperidone. The cognitive factor showed significant improvement for all atypicals, as did the depression/anxiety factor. Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone. CONCLUSIONS: Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure. However, antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains (positive, cognitive, and depression/anxiety) of schizophrenia. Clozapine and olanzapine also showed improvement on the negative factor. Only clozapine was associated with improvement on the excitement domain. This finding confirms that atypicals are associated with improvement of an expanded spectrum of symptoms in treatment-resistant patients.     

Factors Involved in Making Decisions to Prescribe Medications for Psychiatric Disorders by Psychiatrists: A Survey Study

The objective of this study is to understand psychiatrist's decisions to prescribe psychiatric medications. A survey questionnaire was prepared consisting of 15 factors. Each factor had a five-point Likert scale, rating the importance of each factor in making decisions to prescribe medications. Twenty-six psychiatrists at a state psychiatric hospital completed the questionnaire. The data analysis involved the frequencies of responses for each factor being compared using Chi square goodness-of-fit tests with null hypothesis that the response distribution will be centered around average score of three on the Likert scale. All the participants rated patient's symptom, severity, and diagnosis as the most important. This was followed by the patient's past experience with medications, then medication side effects, concurrent physical health problems, and medication interactions. Psychiatrist's experience with medications rated as more important than evidence from clinical trials. Finally, psychiatrists integrate evidence from research findings with personal experience, patient preferences, and clinical context in making decisions in prescribing medications for psychiatric disorders.     

Priapism associated with conventional and atypical antipsychotic medications: a review.

BACKGROUND: Priapism is a prolonged, usually painful, and persistent penile erection not usually associated with sexual stimuli, resulting from a disturbance in the normal regulatory mechanisms that initiate and maintain penile flaccidity. This infrequent adverse event of antipsychotic medication use requires emergency evaluation and has potentially serious long-term sequelae including erectile dysfunction. Clinicians prescribing antipsychotic medications should be aware of this rare but serious adverse event. METHOD: A computerized search, using the MEDLINE database (1966-summer 2000), located cases of priapism associated with most conventional antipsychotics as well as with clozapine, risperidone, and olanzapine. The search included no restrictions on languages. Keywords included priapism combined with antipsychotic agents and the names of the currently available atypical antipsychotics. Twenty-nine publications were located using these parameters. Additional publications were reviewed for general background on pathophysiology, evaluation, and management. The quality of the evidence reviewed is limited by the observational and uncontrolled nature of case reports, case series. and review articles. RESULTS: Psychotropic-induced priapism is currently believed to be caused by the alpha1-adrenergic antagonism of these medications. Detumescence is sympathetically mediated, and alpha1-adrenergic antagonism (within the corpora cavernosa) inhibits detumescence. The propensity of individual antipsychotics to induce priapism can presumably be estimated on the basis of alpha1adrenergic blockade affinities. Of the conventional antipsychotics, chlorpromazine and thioridazine have the greatest alpha1-adrenergic affinity and have been most frequently reported to be associated with priapism. Of the atypical antipsychotics, risperidone has greater alpha1-adrenergic affinity, although 3 of the 5 currently U.S. Food and Drug Administration (FDA)-approved atypicals have been reported to be associated with priapism. CONCLUSION: Virtually all antipsychotic medications have been reported to rarely cause priapism due to their alpha-adrenergic antagonism. This adverse event should be considered a urologic emergency. Clinicians should be familiar with this infrequent serious adverse event of antipsychotic medications.     

Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles

We characterized prescribing in Connecticut's State public mental health system to assess the feasibility of implementing an evidence-based medication algorithm. Medication records for a random sample of outpatients with diagnoses of schizophrenia spectrum disorders showed prescribing patterns similar to the entire United States. The base rate of changing antipsychotic medications was moderate. Over half of patients received decanoate medications, polypharmacy was nontrivial, and there was variability in prescribing patterns across physicians. Caucasian patients were more likely to receive an atypical antipsychotic and less likely to have a decanoate medication, and Latino patients were less likely to change medications. Because the base rate of changing medications was moderate and a considerable proportion of patients were prescribed newer antipsychotic medications, introducing a research-derived medication algorithm with newer atypical antipsychotics as first line agents may fit well with current practice. Further, implementing such an algorithm may reduce racial and ethnic disparities in prescribing patterns.     

Survey of Atypical Antipsychotic Medication Use by Child and Adolescent Psychiatrists

Background:  Atypical antipsychotics could be replacing traditional antipsychotics in the treatment of childhood disorders.
Method:  A postal survey was conducted of Child Psychiatrists in a region of the United Kingdom to evaluate their use of atypical antipsychotics for psychotic and non-psychotic conditions.
Results:  97% of respondents reported prescribing atypical antipsychotics and at least 65% did so for non-psychotic indications although several concerns were raised. Differences in prescribing and monitoring practices between Community and Specialist services were noted.
Conclusions:  Atypical antipsychotics appear to play a significant role in current child psychiatry practice. Further discussions and research needs to occur about their use and guidelines produced.     

In the Aftermath of CATIE: How Should Administrators Value Atypical Antipsychotic Medications?

The wide scale use of expensive atypical antipsychotic medications has led to a dramatic increase in the proportion of direct costs schizophrenia being allocated for medications. Although there is evidence that the atypical antipsychotic, clozapine, may lead to cost savings in patients with refractory schizophrenia the cost-effectiveness of the other atypical antipsychotics remains in question. We therefore reviewed the published, long-term randomized, prospective cost-effectiveness treatment studies that compared an atypical to a typical antipsychotic. There were serious methodological problems with all. In general, those that were based on efficacy trials showed an advantage for atypicals while those based on effectiveness studies found the opposite. It appears that to the extent that studies mimic “real world” conditions they fail to support the cost-effectiveness of the atypical antipsychotics.     

Side effects as influencers of treatment outcome

Research relative to the efficacy of a therapeutic agent commands a clinician's greatest interest, but treatment decisions are made based on optimizing efficacy and tolerability/safety considerations. Second-generation atypical antipsychotic drugs are a study in the importance of taking a careful look at the full benefit-risk profile of each drug. The disorders that atypical antipsychotics are approved to treat--schizophrenia, schizoaffective disorder, and bipolar disorder--are associated with an increased rate of certain medical comorbidities compared to the general population. Between-drug differences in efficacy are relatively modest for the atypicals, or between atypicals and conventionals, while differences in safety and tolerability are larger and more clinically relevant. The current article will provide a brief summary of safety-related issues that influence treatment outcome and choice of drug.     

Antipsychotics: Past and Future: National Institute of Mental Health Division of Services and Intervention Research Workshop, July 14, 1998.

A workshop on "Antipsychotics: Past and Future" was convened by the National Institute of Mental Health (NIMH), Division of Services and Intervention Research (DSIR), on July 14, 1998, to review the results of recent antipsychotic drug research, discuss current standards of treatment, and identify areas needing further study. There has been a proliferation of new antipsychotic medications and a rapid increase in their clinical utilization. The new atypicals are beginning to supplant the older typical neuroleptic antipsychotics, and the scientific and ethical issues raised by this transition prompted the workshop. Given the apparent, albeit not fully defined, advantages of atypical drugs, particularly their safety profiles, the question is whether more comparisons with typical antipsychotics are warranted and whether clinical trial designs warrant (or would be justified in) the inclusion of typical drugs as standard active comparators. Workshop participants--including clinical researchers, patient advocates, bioethicists, and NIMH staff--discussed the conclusions drawn from current data, ethical issues for subjects in clinical trials, funding for ongoing studies using typical agents, and appropriate comparators for trials using atypical agents.