Ric M. Procyshyn

Antipsychotic Polypharmacy: A Survey of Discharge Prescriptions from a Tertiary Care Psychiatric Institution

Objective: To perform a retrospective survey of discharge medications at a tertiary care psychiatric facility and to assess the incidence of antipsychotic polypharmacy. Method: This is a retrospective survey that used the Department of Pharmacys computer database to obtain relevant discharge information on all nongeriatric patients with schizophrenia discharged from Riverview Hospital between November 1, 1996 and October 31, 1998. From a total of 492 eligible patients, 229 met the inclusion criteria and formed the database for the survey. Results: The main finding of the survey was that 27.5% of our discharged patients diagnosed with schizophrenia left our facility on an antipsychotic polypharmacy regimen. Compared with patients discharged on a single antipsychotic, the pooled data revealed a significantly greater use of anticholinergic agents in those patients prescribed an antipsychotic polypharmacy regimen. Further, of the atypical agents, only risperidone showed a statistically significant reduction in dosage when coprescribed with a second antipsychotic. Conclusion: Although antipsychotic polypharmacy persists today, as it has over the past 30 years, evidence-based data to support this controversial treatment strategy is lacking. As a result clinicians are relying on their clinical experience, and perhaps intuition, to design antipsychotic polypharmacy treatment protocols. Efforts should be made to replace subjective clinical impression with a more rational approach to antipsychotic polypharmacy—one that is based on pharmacodynamic and pharmacokinetic understanding of drug action.

Methamphetamine use: a comprehensive review of molecular, preclinical and clinical findings.

Methamphetamine (MA) is a highly addictive psychostimulant drug that principally affects the monoamine neurotransmitter systems of the brain and results in feelings of alertness, increased energy and euphoria. The drug is particularly popular with young adults, due to its wide availability, relatively low cost, and long duration of psychoactive effects. Extended use of MA is associated with many health problems that are not limited to the central nervous system, and contribute to increased morbidity and mortality in drug users. Numerous studies, using complementary techniques, have provided evidence that chronic MA use is associated with substantial neurotoxicity and cognitive impairment. These pathological effects of the drug, combined with the addictive properties of MA, contribute to a spectrum of psychosocial issues that include medical and legal problems, at-risk behaviors and high societal costs, such as public health consequences, loss of family support and housing instability. Treatment options include pharmacological, psychological or combination therapies. The present review summarizes the key findings in the literature spanning from molecular through to clinical effects.

Persistent antipsychotic polypharmacy and excessive dosing in the community psychiatric treatment setting: a review of medication profiles in 435 Canadian outpatients.

OBJECTIVE The present study aimed (1) to determine the proportion of patients treated with persistent antipsychotic polypharmacy in an outpatient population and (2) to determine if persistent antipsychotic polypharmacy is associated with excessive dosing. METHOD Using a province-wide network that links all pharmacies in British Columbia, Canada, to a central set of data systems, we identified community mental health outpatients who had been treated with the same pharmacologic regimen for at least 90 days. Apart from antipsychotics, data collection included anticholinergics, antidepressants, mood stabilizers, benzodiazepines, lipid-lowering agents, and antidiabetic agents. Demographic data including sex, age, and diagnosis were obtained from the patients chart. In order to compare dosages of the various antipsychotics we used a fixed unit of measurement based on dividing the prescribed daily dose (PDD) by the defined daily dose (DDD). A PDD/DDD ratio greater than 1.5 was defined as excessive dosing. RESULTS Four hundred thirty-five patients met the inclusion criteria and were included in the analysis. Overall, the prevalence of persistent antipsychotic polypharmacy was 25.7% for the entire cohort. The prevalence of persistent antipsychotic polypharmacy was highest for patients with schizoaffective disorder (33.7%), followed by schizophrenia (31.7%), psychosis not otherwise specified (20.0%), bipolar disorder (16.9%), and major depression (14.3%). The mean +/- SD PDD/DDD ratio for all patients prescribed persistent antipsychotic polypharmacy was not only excessive, it was significantly greater compared to that of patients receiving antipsychotic monotherapy (1.94 +/- 0.12 vs 0.94 +/- 0.04, P < .005). CONCLUSIONS Using a diagnostically heterogeneous outpatient population, this study is, we believe, the first to report that persistent antipsychotic polypharmacy is associated with excessive dosing, in and of itself as well as compared to antipsychotic monotherapy.

Cardiovascular side-effects of antipsychotic drugs: the role of the autonomic nervous system.

Cardiovascular disease is the leading cause of death in people with severe mental disorders, and rates are proportionally greater than for other diseases such as cancer. Reports of sudden death in patients receiving antipsychotic treatment have raised concerns about the safety of antipsychotic drugs, leading to a number of recent changes in how such drugs are advertised and marketed. The majority of second generation antipsychotic drugs also have significant metabolic side-effects, such as weight gain, insulin resistance and hyperlipidemia, which may contribute indirectly to cardiovascular complications. As the use of antipsychotic drugs continues to expand into new indications and populations such as children and adolescents, a better understanding is needed of how antipsychotic drugs affect the cardiovascular system. Antipsychotic drugs interact with numerous receptors both centrally and peripherally, including monoamine receptors. The direct, non-specific pharmacological actions of antipsychotic drugs can lead to adverse cardiovascular effects, including orthostatic hypotension, tachycardia and ventricular arrhythmias. The mechanisms responsible for these antipsychotic-induced cardiovascular abnormalities have not been fully elucidated, but likely involve blockade of adrenergic or cholinergic receptors and hERG channels, in addition to impaired autonomic function. The direct and indirect effects of antipsychotic drugs on the cardiovascular system and their possible mechanisms of action are discussed in this review, where both preclinical and clinical findings are integrated.

Self-reported motivation to smoke in schizophrenia is related to antipsychotic drug treatment

PURPOSE The prevalence of smoking in schizophrenia has reliably been reported as being higher than for any other psychiatric disorder. While a number of theories have been proposed to account for such high rates of smoking, little is known about the subjective motivation for why schizophrenia patients smoke in comparison with those without the disease. OBJECTIVES The aim of the present study was to evaluate and compare smoking motivation in control subjects and schizophrenia patients, and determine if factors such as type of medication or access to cigarettes could contribute to self-reported motivation for smoking. METHODS We assessed motivation to smoke in 61 schizophrenia inpatients and 33 non-psychiatric health worker controls at a tertiary care psychiatric facility in a cross-sectional study. Nicotine dependency and smoking behavior were evaluated using the Fagerstrom Test for Nicotine Dependence and a validated questionnaire that assesses motivation for smoking along seven different dimensions. RESULTS Schizophrenia patients reported a stronger motivation to smoke than controls for reasons related to pleasure from the act of smoking, as well as a need for psychomotor stimulation. Scores on both these factors were significantly associated with daily antipsychotic drug dose. The sedative and anxiolytic effects of smoking were related to anticholinergic load of psychiatric medications. CONCLUSION The findings highlight important differences in self-reported motivation to smoke between schizophrenia patients and normals. Antipsychotic drugs may also influence aspects of motivation to smoke.

A parametric study of the acute effects of antipsychotic drugs on glucose sensitivity in an animal model

The therapeutic use of atypical antipsychotics is associated with a high incidence of metabolic side-effects. In the present study we examined the acute effects of both high and low-dose atypical antipsychotic drugs and one typical drug on alterations in glucose and insulin parameters using a rodent model. The effects of administration of clozapine (2mg/kg; 20mg/kg), olanzapine (1.5mg/kg; 15 mg/kg), risperidone (0.5mg/kg; 2.5mg/kg) and haloperidol (0.1mg/kg; 1.0mg/kg) on glucose sensitivity and insulin resistance were determined through HOMA-IR values in fasted rats and glucose clearance during a glucose tolerance test. Acute effects were determined 60, 180 or 360 min following drug administration. The atypical antipsychotics produced significant dose and time dependent effects on fasting plasma glucose and insulin concentrations, HOMA-IR values, insulin resistance and glucose intolerance. The greatest effect on glucose dysregulation was noted primarily with clozapine and olanzapine; however, all four treatments caused significant increases in fasting glucose and/or insulin levels with the high dose, 60 min post-drug administration. Together, these findings indicate that acute administration of antipsychotic drugs has potent effects on metabolic regulation of glucose and insulin sensitivities, which may contribute to metabolic side-effects seen in humans.

Drug utilization patterns and outcomes associated with in-hospital treatment with risperidone or olanzapine

This study compared the drug-utilization costs and indicators of clinical outcomes associated with the use of risperidone and olanzapine in a hospital setting. We conducted a nonrandomized, retrospective chart review of consecutive patients identified as presenting with psychotic symptoms on inpatient wards at Riverview Hospital in British Columbia and given either risperidone or olanzapine as their first new drug after reassessment (n = 30 per treatment group). Data were collected for up to 120 days. No significant differences were observed between groups in terms of sex, age, duration of illness, or diagnosis. The mean dosage of risperidone for responders was 4.89 +/- 2.56 mg/d, whereas that for olanzapine was 17.19 +/- 3.88 mg/d. The associated daily drug-acquisition costs were significantly different, at CA

Concomitant clozapine reduces smoking in patients treated with risperidone

4.69 for risperidone and CA

Prevalence and Outcomes of Pharmaceutical Industry—Sponsored Clinical Trials Involving Clozapine, Risperidone, or Olanzapine

11.52 for olanzapine. Notes in patient charts indicated that a significantly greater proportion of risperidone-treated patients (60.0%) than olanzapine-treated patients (26.7%) responded to therapy, as indicated by improvement in at least one target symptom (P < 0.01). Forty percent of patients initially treated with risperidone were discharged on their original therapy, compared with 13.3% of patients treated with olanzapine (P < 0.05). These results were not substantially affected by correction for markers of illness severity or treatment resistance. Overall, no significant differences in side effects were recorded in the patient records of the two groups. Within this cohort of patients, risperidone treatment was associated with lower drug-acquisition cost and better treatment outcomes than olanzapine.

Smoking cessation interventions among individuals in methadone maintenance: A brief review

This pilot study examines the smoking behaviors of patients treated with either risperidone alone or in combination with clozapine. Smoking behavior was evaluated using expired carbon monoxide (CO) measurements, the Fagerstrom Test for Nicotine Dependence (FTND), and a semi-structured interview. Our results indicate that patients co-prescribed clozapine with risperidone smoke significantly less than patients treated with risperidone alone (19.1+/-9.3 vs. 37.8+/-19.1 ppm CO, respectively, P=0.03). These data are consistent with previous studies showing that clozapine treatment is associated with significantly reduced smoking behavior relative to other antipsychotic agents.