Suicide by antidepressant intoxication identified at autopsy in Vienna from 1991–1997: the favourable consequences of the increasing use of SSRIs

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Abstract

In the area of Vienna, any person dying under questionable circumstances is examined at the Institute of Forensic Medicine, where the cause of death is determined by means of autopsy and chemical analysis. Our study on fatal intoxications was performed in the period between 1991 and 1997, when selective serotonin reuptake inhibitors (SSRIs) were establishing themselves on the market, reaching the top of prescription statistics. Tricyclic antidepressants (TCAs) were involved in 30 single- and 127 multiple-substance intoxications, with amitriptyline and doxepin being the most frequently used drugs. SSRIs were involved in five multiple-substance intoxications. The f-value, which refers to the number of deaths per million defined daily doses prescribed, was found to be significantly (P≤0.001) higher in TCAs than in SSRIs. The f-value for the total group of all antidepressants declined significantly (P≤0.05) during the observation period of 7 years. In conclusion, SSRIs turned out to be less toxic than TCAs, and the increasing use of new antidepressants did not coincide with an increased number of deaths caused by these drugs.

Introduction

Depressive disorders have been found to be significant risk factors for suicide (Lee and Murray, 1988, Cheng, 1995). Certain antidepressants can be used both as a remedy for depression and as a device for a suicide attempt (Kasper et al., 1996). The side-effect profile of tricyclic (or tetracyclic) antidepressants (TCAs) is based on anticholinergic, antihistaminergic and anti-α1-adrenergic properties (Kasper et al., 1994, Richelson, 1994, Bauer and Berghöfer, 1997). Cerebral depression, convulsion, ventricular arrhythmia and respiratory failure are classic symptoms of intoxication with TCAs (Hulten, 1990). Consequently, new antidepressants which cause less side-effects or complications than TCAs have been developed. During the last 10 years, selective serotonin reputake inhibitors (SSRIs) and a reversible monoamine oxidase inhibitor – moclobemide – have been introduced in Europe and have more or less conquered the market (Ohberg et al., 1998, Isacsson et al., 1999).

Several authors have presented the mortality statistics for antidepressants and calculated indices to determine the relative toxicity of different medications. Their calculations were based on the number of deaths either per kilogram of a drug or per million defined daily doses (standard quantity units) prescribed (Cassidy and Henry, 1987, Farmer and Pinder, 1989, Henry, 1989, Henry et al., 1995, Ohberg et al., 1995). Additionally, the fatal toxicity index (FTI) was defined as the number of deaths caused by an antidepressant divided by the number of prescriptions (in millions) of this drug during a given period of time. The FTI has been shown to be significantly higher for TCAs than for the recently introduced SSRIs (Henry et al., 1995, Henry, 1997), leading the authors to conclude that switching to medications with a low index would reduce the number of lethal incidents. Barraclough (1974) applied the same approach to study deaths caused by hypnotic drugs and barbiturates.

Vienna (1.7 million inhabitants) provides ideal conditions for pharmaco–epidemiological studies. First, the Institute of Forensic Medicine has been appointed to the investigation of all cases of sudden and unexpected death. Thus, in all victims, the cause of death is determined by means of a comprehensive post-mortem examination. This is in contrast to studies in the United Kingdom (Henry et al., 1995) based on mortality statistics without specification of how the cause of death was established in the huge study population. Second, a reliable indicator of the availability of psychotropic prescriptions can be obtained from the main public health insurance company “Wiener Gebietskrankenkasse” (WGKK), which in the area of Vienna provides insurance for 1.06 million employed and retired people and an unknown number of their children and spouses. In Austria, antidepressants are only available from a pharmacy on prescription by a general practitioner or specialist.

The aim of the study was to compare fatality risks of various antidepressants by presenting the number of autopsy-proved antidepressant intoxications in relation to prescriptions. We hypothesized that between 1991 and 1997, the number of fatal intoxications per million defined daily doses of all antidepressants prescribed would decrease as a result of changing psychopharmacological strategies among physicians.

Section snippets

Prescription of antidepressants

The public health insurance company WGKK entrusted the authors with data on prescriptions of psychotropic drugs issued in the area of Vienna between 1991 and 1997. Information on the number of oral formulations, dosage units, package size and form of medication (tablets, capsules, syrup or suspension) was provided. The quantity (in kilograms=kg) of drugs prescribed was then calculated from these data.

Post-mortem examination at the Institute of Forensic Medicine

The exploration of the cause of death included the victim’s medical and social history, reports

Prescriptions

Table 1 shows a ranking of antidepressants according to their NDDD (q/DDD) prescribed in the period from 1991 to 1997. It can be seen that amitriptyline was sold in a much greater quantity (q in kg) than citalopram, but citalopram was ranked first because the DDD of the SSRI is remarkably lower than that of the TCA (20 mg vs. 75 mg).

From 1991 to 1997, the quantity of TCAs prescribed decreased steadily by 16% (R=−0.99, P≤0.0001), from 325 kg to 273 kg (Table 2). SSRI prescriptions increased

Discussion

From 1991 to 1997, the number of antidepressants prescribed in Vienna more than doubled. The same development was shown by epidemiological studies performed in Scandinavia (Isacsson et al., 1997, Isacsson et al., 1999, Ohberg et al., 1998). Our investigation demonstrated that consumption of SSRIs increased by 780%, and they became the most frequently prescribed antidepressive medication in 1996. In contrast, the use of TCAs decreased by 16% during the same period.

Systematic investigations based

Acknowledgements

The authors are obliged to the Wiener Gebietskrankenkasse (WGKK) for supplying data concerning the prescription of psychotropic drugs in the area of Vienna. We would also like to thank Mr. Michael Scherer for performing statistical analysis and Mag. Elisabeth Grätzhofer for her valuable help in writing this manuscript in English.

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    Corresponding author for chemical analysis. Tel.: +43-1-4277-65765; fax: +43-1-4277-9657.

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