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OBJECTIVE: To describe a case in which concurrent treatment with nefazodone was associated with an elevation in the plasma concentration of zopiclone, possibly resulting in enhanced hypnosedative efficacy. CASE REPORT: An 86-year-old white woman was treated with nefazodone for depression. Zopiclone was also introduced for the management of insomnia, but she subsequently experienced morning drowsiness. The concentration of zopiclone in plasma was subsequently measured eight hours after administration on two occasions, during nefazodone therapy and after its withdrawal. After discontnuation of nefazodone, the plasma concentration of the S-enantiomer of zopiclone decreased from 107 to 16.9 ng/mL, while the R-enantiomer plasma concentration decreased from 20.6 to 1.45 ng/mL. DISCUSSION: Nefazodone is a relatively potent inhibitor of CYP3A4, a hepatic isoenzyme thought to play a major role in the metabolic elimination of zopiclone. The substantial decrease in the plasma zopiclone concentrations observed after withdrawal of nefazodone likely reflects a drug interaction. Despite the normally short elimination half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction may have clinical significance. CONCLUSIONS: The features observed in this case suggest the possibility of a drug-drug interaction between nefazodone and zopiclone. Further prospective investigation is required to elucidate the nature and magnitude of this effect.

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Selected clinical pharmacy interventions undertaken during a 30-day data capture period were analysed, seeking to gain a greater understanding of the nature of the drug-related problems involved. Pharmacists were asked to record only interventions that were of potentially major significance. A total of 67 interventions were submitted for analysis. In 28 cases (41.7% of the initial total) the intervention reports were excluded from further analysis after initial review. For the remaining 39 interventions, 20 patients (51%) were under the care of a medical unit, and cardiovascular/antithrombotic agents accounted for 17 reports (43.5%). The majority of interventions were implemented at the time of inpatient medication order review by the clinical pharmacist (n=25, 64%). The most common category of drug-related problem addressed in the interventions related to the prescription of inappropriately high doses of the correct drug for the patient (n=17, 43.6%). Deficiencies in technical knowledge accounted for less than 25% of all cases.

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OBJECTIVE: To examine characteristics of tranquilizer use in a cohort of Australian Vietnam War veterans. DESIGN: Prospective analysis of medication use and assessment of social and clinical variables, including tranquilizer dependence. PATIENTS: Fifty-one Australian Vietnam War veterans were recruited from the department of psychiatry of an Australian teaching hospital. All subjects were men, with a mean +/- SD age of 52.2 +/- 3.3 years. MAIN OUTCOME MEASURES: A structured interview was used to obtain details of medical and psychiatric history, medication use, substance use, forensic history, and health service utilization data. Anxiety was assessed using the Hamilton Anxiety Rating Scale (Ham-A). A validated tranquilizer dependence rating scale was administered for each patient. RESULTS: Commonly used tranquilizers included diazepam (n = 19 patients) and zopiclone (26). Most patients (44) reported the use of one or more drugs for the purpose of nighttime sedation, while exclusive daytime use of tranquilizers for anxiolytic effect was uncommon. The median time spent in the hospital during the preceding year was 21.0 +/- 56.8 days. Symptoms of anxiety were prevalent, with a mean Ham-A score of 35.5 +/- 7.8. Screening criteria suggestive of tranquilizer dependence were met in 34 subjects. Health service utilization was correlated with tranquilizer intake and overall medication use. Tranquilizer dependence was independently associated with cigarette smoking (p = 0.039; odds ratio = 5.13, 95% CI 1.08 to 24.33). CONCLUSIONS: This study provides insight into the nature of tranquilizer use in an Australian population of Vietnam War veterans. The extensive use of these drugs suggests that further research and possibly intervention in this area is needed.

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Drug interactions are a common and serious problem arising from polypharmacy. Strategies to reduce the likelihood of the co-prescription of hazardous drug combinations are likely to enhance the quality of care provided for patients requiring polypharmacotherapy. Drugs for which patient-oriented information strategies may decrease the likelihood of drug interactions tend to be those of low therapeutic index. and have interaction potential with other drugs commonly prescribed or available without prescription.

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OBJECTIVE: The aim of this paper is to report a case of symptomatic methadone toxicity associated with fluvoxamine treatment. CLINICAL PICTURE: A 28-year-old woman was admitted to hospital with severe hypoxaemia and hypercapnia indicating hypoventilation. Medication prior to admission had been stable and included methadone 70 mg daily and diazepam 2 mg twice daily. Three weeks before admission she had commenced treatment with fluvoxamine. TREATMENT: Methadone was decreased to 50 mg daily and diazepam was tapered to zero. OUTCOME: The serum methadone concentration decreased and oxygenation improved considerably. CONCLUSIONS: Clinicians should be aware of the potential for a significant drug interaction between fluvoxamine and methadone.

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OBJECTIVE: To undertake a qualitative analysis of calls regarding psychotropic drugs that were received during a national medicines phone-in day. BACKGROUND: In July 1996, The Society of Hospital Pharmacists of Australia coordinated a national medications phone-in day, allowing consumers to seek information about medications from pharmacists and physicians using a toll-free telephone number. METHODS: Data collection forms were used to record the details of all calls answered during the phone-in day. Demographic data collected included the estimated age and gender of the caller. Other data collected included the drugs that were the subject of the inquiry and the category of questions. RESULTS: There were 42,096 attempted connections to the service, but because of limited telecommunications capacity, only 2245 callers were successfully connected. Psychotropic drugs were the primary subject of 367 calls, representing 16.4% of all inquiries for which data collection forms were completed. Antidepressants (56.1%) and benzodiazepines (24.8%) were the two most commonly encountered classes of psychotropic drugs. The greatest proportion of calls (57.2%) was related to adverse effects of medications. The nature of the inquiries regarding adverse drug effects was generally consistent with the adverse effects detailed in the scientific literature. CONCLUSIONS: The results of this 1-day, consumer-oriented drug information project suggest that there is a substantial need for this type of service. Patients treated with psychotropic medications should have access to unbiased, high-quality information about drug therapy.

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OBJECTIVE: To report two cases of perhexiline toxicity associated with selective serotonin re-uptake inhibitor (SSRI) treatment. CLINICAL PICTURE: Serum perhexiline concentrations progressively increased after a 69-year-old man was concurrently prescribed paroxetine for the treatment of depression. An 84-year-old woman was admitted to hospital with severe, symptomatic perhexiline toxicity associated with fluoxetine treatment. TREATMENT: In both cases, perhexiline therapy was suspended and treatment with SSRIs was withdrawn. OUTCOME: Serum perhexiline concentrations declined following the withdrawal of paroxetine in one case, but in the case of the second patient perhexiline concentrations were extremely slow to decrease, resulting in referral to a rehabilitative care unit for convalescence. CONCLUSIONS: Serum perhexiline concentrations may be elevated during concurrent treatment with SSRIs, potentially resulting in severe toxicity.

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OBJECTIVE: To document a case in which the administration of itraconazole was associated with an apparent decrease in digoxin clearance, resulting in an increase in the serum digoxin concentration. CASE SUMMARY: A man receiving digoxin for atrial fibrillation was concurrently treated with itraconazole 200 mg/d for esophageal candidiasis. The estimated urinary digoxin clearance was decreased during this combination therapy. DISCUSSION: Digoxin is primarily cleared by the kidneys, and the mechanism of renal clearance involves both glomerular filtration and tubular secretion. We postulate that itraconazole or a metabolite of this compound may have resulted in decreased tubular secretion of digoxin, accounting for decreased urinary digoxin clearance. CONCLUSIONS: Monitoring of serum digoxin concentrations should be performed if patients taking digoxin are treated with itraconazole. Further investigation is necessary to elucidate the nature of the interaction between digoxin and itraconazole.

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Clinical practice guidelines may take a variety of forms, and their role in contemporary health care continues to be debated. Practice guidelines may provide assistance for health-care workers in optimizing the quality of patient care. The complexity and diversity of contemporary pharmacy practice has necessitated the development of practice guidelines which will assist pharmacy departments in providing high quality, customer-focussed pharmaceutical services.

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A standardized data collection form was developed to enable uniform documentation of all clinical pharmacy interventions undertaken for an acute-care, psychiatric inpatient population during a 6-month study period. This information included demographic data as well as details of the drugs involved, the nature of the drug-related problems, the type of intervention and an estimate of the significance of the intervention. A total of 204 clinical interventions were proposed for 69 patients (mean age 66.8 years, range 28-85 years). The proposed interventions were accepted by medical staff in 187 (91.7%) instances. Antidepressants were the class of drug most often generating clinical interventions (34.7% of total interventions). The most common type of intervention was a recommendation for the commencement of drug therapy (28.8%), followed by recommendations for enhanced patient monitoring (23.5%). In 20.3% of cases the interventions were estimated to be of major significance. This study suggests that the provision of clinical pharmacy services in the acute-care, adult, psychiatric setting has the potential to generate a considerable range of interventions aimed at optimizing treatment outcomes.

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OBJECTIVE: To describe a patient in whom the administration of tiaprofenic acid and fosinopril was associated with decreased lithium clearance, resulting in increased serum lithium concentrations. CASE SUMMARY: A woman treated with lithium for bipolar affective disorder was concurrently treated with tiaprofenic acid 200 mg tid for shoulder pain. Previously initiated treatment with fosinopril was maintained during this time. The urinary lithium clearance was decreased during this combination therapy, necessitating a reduction in the lithium dosage. DISCUSSION: Lithium is approximately 80% reabsorbed in the proximal tubule, and the addition of tiaprofenic acid may have resulted in enhanced tubular lithium reabsorption. The possible influence of concurrent fosinopril therapy may also have contributed to altered lithium pharmacokinetics in this case. CONCLUSIONS: Serum lithium concentrations should be monitored if patients taking lithium are treated with tiaprofenic acid.

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OBJECTIVE: To examine the hematologic safety profile of the selective serotonin reuptake inhibitors (SSRIs), with particular emphasis on the effects of these drugs on platelet aggregation. METHODS: Platelet aggregation studies were undertaken at baseline, and repeated 2 and 4 weeks after the initiation of treatment with an SSRI. Other investigations undertaken included analysis of serum electrolyte and liver enzyme concentrations, complete blood count, and coagulation studies. Patients were also assessed for clinical signs of bleeding. Eight patients (7 treated with fluoxetine, 1 with paroxetine) completed the study protocol. RESULTS: Repeated ANOVA revealed no abnormalities in platelet aggregation, hematopoiesis, or coagulation profile. No patient developed clinical signs of abnormal hemostasis during the study period. A statistically significant elevation in the mean serum bilirubin concentration was detected, but this was not of clinical significance. CONCLUSIONS: Although the SSRIs may cause abnormal hemostasis, this effect is probably rare. Another possibility is that abnormal hemostasis is more likely to occur when high doses of SSRIs are administered.

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