Peter McManus

Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis

Abstract Objective: To examine the association between trends in antidepressant prescribing and suicide rates in Australia for 1991-2000. Design: Analysis of databases of suicide and rates of antidepressant prescribing according to age and sex. Setting: Australian Bureau of Statistics data, sales data from the Australian pharmaceutical industry, prescribing data in general practice. Subjects: Men and women aged 15 years and over in 10 year age groups. Main outcome measures: Trends in suicide rates and trends in antidepressant prescribing. Association measured by Spearmans rank correlations. Results: While overall national rates of suicide did not fall significantly, incidence decreased in older men and women and increased in younger adults. In both men (rs=−0.91; P<0.01) and women (rs=−0.76; P<0.05) the higher the exposure to antidepressants the larger the decline in rate of suicide. Conclusions: Changes in suicide rates and exposure to antidepressants in Australia for 1991-2000 are significantly associated. This effect is most apparent in older age groups, in which rates of suicide decreased substantially in association with exposure to antidepressants. The increase in antidepressant prescribing may be a proxy marker for improved overall management of depression. If so, increased prescribing of selective serotonin reuptake inhibitors in general practice may have produced a quantifiable benefit in population mental health. What is already known on this topic There has been a substantial increase in antidepressant prescribing by general practitioners in Australia since the introduction of selective serotoin reuptake inhibitors in the early 1990s Previous studies have indicated an association between increased antidepressant prescribing and reduced suicide rate What this study adds In Australia the rate of suicide fell in older people, the age group most heavily exposed to antidepressants Most antidepressants are now prescribed by general practitioners The association may indicate the improved treatment of depression by general practitioners

Prescription Drug Utilization Following Patient Co-Payment Changes in Australia

In November 1990 major patient co‐payment changes were introduced into the Pharmaceutical Benefits Scheme (PBS), which accounts for around 90% of all community prescriptions in Australia. Interrupted time series analyses were performed to assess the impact of these co‐payment changes on the prescription levels of defined groups of ‘discretionary’ and ‘essential’ drugs for both the general community and for a subgroup comprising elderly returned servicemen and women. While the co‐payment changes themselves had a significant immediate effect on lowering the use of both categories of drugs, the effects were substantially larger for the ‘discretionary’ groups in both cases. Notably there was a clear post‐intervention trend for increased prescriptions of ‘essential’ drugs after the initial decline, which was not evident for the ‘discretionary’ drugs. The introduction of programmes to compensate high risk groups in Australia may have enabled the co‐payment to become a more selective policy instrument than has been shown in other settings.

Use of Antidepressants by General Practitioners and Psychiatrists in Australia

Objective: To examine the antidepressant prescribing patterns of psychiatrists and general practitioners (GPs) in Australia, focusing specifically on: the prescribed daily dose, the relative proportions (from subsidized dispensing data) of prescriptions written, and how these proportions change over time for a newly listed antidepressant drug (using paroxetine as an example). Method: Retrospective analyses of subsidized claims data (comprising nearly 90% of the community supply of antidepressants) and prescriber surveys. Results: General practitioners prescribe 86% of subsidized antidepressants in Australia. Almost three-quarters of the antidepressant prescriptions prescribed in primary care management are also initiated by a GP. Psychiatrists prescribed higher doses than general practitioners for all the antidepressants examined. For paroxetine, a higher than average proportion of scripts were written by psychiatrists when the drug was initially available and it only reached the GP/psychiatrist split seen with an established drug in the same therapeutic class (fluoxetine) four years after marketing. The most prominent type of depression that GPs believed they were treating was ‘chronic mild depression’, which contrasts with the subsidized indication for all newer antidepressant classes of ‘major depressive disorders’. Conclusions: General practitioners are the major providers of treatment for depression in Australia. When writing prescriptions for tricyclic antidepressants GPs use doses lower than those recommended for major depression, however, most management in primary care is not for conditions regarded by the GP as major depression. A significant number of prescriptions for the newer antidepressants may not accord with the Pharmaceutical Benefits Scheme (PBS) restrictions for use.

Changes in fatalities due to overdose of anxiolytic and sedative drugs in the UK (1983-1999)

AbstractObjective: To establish the frequency with which anxiolytic and sedative drugs result in fatal poisonings and to examine longitudinal changes in poisoning deaths. Method: The number of fatal poisonings between 1983 and 1999 in England, Scotland and Wales due to a single anxiolytic or sedative drug was obtained from the Department of Health in the UK. This was divided by the number of prescriptions for these drugs in England and Scotland to derive a fatal toxicity index (FTI) of deaths per million prescriptions. Results: Chloral hydrate, clomethiazole, barbiturates, and related sedatives had much higher FTIs than benzodiazepines, buspirone, zolpidem and zopiclone. There has been a substantial reduction in the annual number of deaths from sedative drug poisoning between 1983 and 1999. This has been due to a sustained reduction in prescriptions for high toxicity drugs and more recently a major reduction in temazepam deaths that coincided with the withdrawal of gelatin capsule formulations.Conclusion: Deaths would be expected to be further reduced if there were reduced prescriptions of high toxicity drugs — and the continuing need for short-acting barbiturates, clomethiazole and chloral hydrate should be questioned.

Can the Fatal Toxicity of Antidepressant Drugs be Predicted with Pharmacological and Toxicological Data

SummaryAntidepressant drugs are among the most common drugs involved in fatal poisoning and large variations between antidepressant drugs have been noted. Despite the fact that a large number of studies have calculated a fatal toxicity index (FTI) for antidepressants, no serious attempts have been made to compare the differences in fatal toxicity against known pharmacological and toxicological differences in receptor affinity. It is potentially from such data that screening of drugs during their preclinical development can be facilitated.We examined correlations between the FTI and noradrenaline (norepinephine)/serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibition selectivity, the dose that is lethal to 50% of animals (LD50), lipid solubility, and antagonist activity at cholinergic, histaminergic, α-adrenergic and γ-aminobutyric acid (GABA)A receptors or sodium and potassium channel blocking effects. We obtained data on the number of fatal poisonings between 1983 and 1992 in England and Wales caused by a single antidepressant drug from the Department of Health in the UK. This number was divided by the number of prescriptions in England for these drugs over this time to derive a FTI of deaths per million prescriptions.The highest FTIs were for amoxapine, viloxazine, desipramine and doth-iepin. Lofepramine, paroxetine and fluoxetine had very low FTIs. Using Poisson regression, there was a significant positive relationship between the FTI of antidepressant drugs and their lethal toxicity in animals, and measures of their cardiac effects. The relative noradrenaline/serotonin reuptake inhibition, lipid solubility and their potency at histamine H1, muscarinic and α1-adrenergic receptors had no substantial association with the FTI. Limited data suggest that some cardiac effects and potency as a GABAA antagonist may be important predictors of significant toxicity. Further data using standardised bio-assays are needed to compare the direct cardiac effects of antidepressants. Thus, the best current preclinical indicator of fatal toxicity in humans is the LD50 in animal studies. Clearly, there are humane and practical reasons for developing a better preclinical indicator of toxicity in overdose for this rapidly expanding group of drugs.

Impact of increasing the re-supply interval on the seasonality of subsidised prescription use in Australia

Objective:To evaluate the impact of increasing the minimum re‐supply period for prescriptions on the Pharmaceutical Benefits Scheme (PBS) in November 1994. The intervention was designed to reduce the stockpiling of medicines used for chronic medical conditions under the PBS safety net.

Examining the adequacy of quantities available for subsidized antidepressant prescriptions in Australia

In Australia the Pharmaceutical Benefits Scheme (PBS), a national drug insurance plan, aims to provide around a months therapy for medication used in chronic conditions. However, there are marked differences among the most commonly used antidepressants in the number of days supply represented by the PBS maximum quantity after adjustment for the defined daily dose (DDD). The DDD is the assumed adult daily dose for a drug and is a WHO drug utilization standard. Whereas the selective serotonin re‐uptake inhibitors (SSRIs) and moclobemide largely provide around a months supply at the DDD, most tricyclic antidepressant (TCA) items provide considerably less than this.