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Eighteen medical examiners, coroners, and forensic science laboratories and offices, representing a total jurisdictional population of 52.6 million, were visited during November 1975, and more than 1200 cases occurring in the four years from 1972 through 31 July 1975 were evaluated for inclusion in the study. The sites were distributed across the United States and Ontario, Canada, and included urban and rural, states, city, and county jurisdictions. Scientific data and circumstantial information was gathered consistently for each case and site by means of five questionnaires. Finally, 1022 cases were compiled and examined, and the data were analyzed to form the body of data from which this report is written. The following conclusions may be drawn. 1. The number of deaths involving propoxyphene is increasing each year, and at a faster rate than total drug deaths. The absolute numbers and rate are different in urban and rural areas, but the frequency reached 6.0 deaths per million population in 1974. Deaths attributed to suicide as well as those determined to be accidental deaths and undetermined have increased. 2. Approximately 66% of all the cases studied had the word propoxyphene included in the cause of death statement on the death certificate. Approximately 46% of the cases were classified as suicide (64% of them female and 36% male), 26% as accidents, and 21% as undetermined. 3. The deceased were mainly middle-class, Caucasian, urban dwellers, with male and female evenly distributed. Their ages were from 20 to 50 years, with few outside this range. Female ages were uniformly distributed, but males in their early twenties were very prominent. This is different from the U.S. population age distribution, which is currently dominated by teenagers. Propoxyphene does not appear to be a pediatric problem, as seen in the study. 4. The deceased were not part of the illegal drug abuse population and had no particular propensity for the use of heroin or narcotics, but rather they were a particular medical population of those who misuse prescription drugs and alcohol. 5. The deceased did have a marked tendency to hypochondria, chronic minor illnesses and emotional problems. Some 43% had recent medical histories, and 82% had a documented psychiatric history which often included (51%) self-destructuve behavior such as suicide attempts. Almost all received a wide range of prescription drugs, particularly tranquilizers, which they often misused in the sense of self-medicating, multiple drug ingestion, and combining alcohol with their medication. Approximately 34% had a history of misusing some drug, and 20% could be defined as abusers in that they were prone to excessive use of their medications; 44% had diazepam available to them, and 17% were either problem drinkers or alcoholics.

A total of 1859 cases provides the basis for this study in which propoxyphene, and often its major metabolite, was demonstrated by toxicological analysis in the blood or tissues of the deceased at 27 medical examiner or coroner's offices across the United States and Canada. The study period includes the last five months of 1975 through December 1978. The cases describe a clearly defined adult population with a marked tendency toward hypochondria, chronic minor illness, and severe psychiatric problems. The high proportion of suicides (44.1% of the total cases and 54.0% of the drug-caused deaths) and multiple-drug toxicities (88.6%) suggests that the involvement of propoxyphene in many of these fatalities may be of less significance than the phenomenon of "polypharmacy" and self-medication without appropriate medical supervision. This evaluation of propoxyphene provides no evidence that propoxyphene is responsible for "street-drug" fatalities. Its appearance in postmortem toxicological examinations has been declining sharply since 1977, but it continues to be dangerous when used excessively, particularly in combination with alcohol and other central nervous system depressant drugs.

Several problems associated with the gas chromatographic determination of DPX and NDPX are discussed and an improved method for their extraction and quantification is described. The method involves two separate extractions, one for DPX with SKF 525A as the internal standard and one for NPDX with dinor-LAAM as the internal standard. The use of two internal standards improved quantitative reproducibility by almost 50%. It was also found that routine DPX and NDPX assays were better determined on packed columns than on capillary columns because the quality of the samples and of the columns was critical. The use of two IS and the double extraction procedure is recommended for general toxicological analyses.

This survey continues and expands earlier studies (Finkle et al., 1976a, b). A total of 27 medical examiner or coroner offices across the USA and Canada were visited. The combined jurisdictional population of these 27 sites is 64.8 million people: 56.5 million people in the USA (27% of the US population) and 8.3 million in Canada (Ontario). Since 1969 through mid-1983, a total of 4412 cases provided information sufficient for inclusion in this study. In each of the cases the presence of propoxyphene, and often its major metabolite, in the blood or tissues of the deceased was confirmed by toxicological analysis at the survey site. The following is a summary of the survey findings: The incidence of propoxyphene-associated deaths reached a peak in 1977, then declined by 22.2% from 1977 to 1978 and by 33.3% from 1978 to 1979, and by a further 10-18% since then. This continuing decline has occurred despite increased interest in propoxyphene misuse and the existence of improved analytical methods for the detection of propoxyphene and its metabolites. The decline is greater than can be accounted for by the decline in propoxyphene prescribing. The most common manner of death was suicide, accounting for about 45% of the cases; it can be safely assumed that the suicides were under-reported. A large majority of the suicides involving propoxyphene were multiple-drug intoxications, including alcohol. Propoxyphene alone was noted in about one-sixth of the suicides. These findings confirm those of the earlier studies, i.e., that a high proportion of the deaths associated with propoxyphene are suicides, and, in most cases, the deceased were victims of multiple-drug toxicity. More than 90% of cases involved persons between the ages of 20 and 40 years. There were very few instances of paediatric, adolescent or older adult deaths associated with propoxyphene. There is no evidence to support the view that the deceased were part of the street drug-abuse population. A history of heroin abuse appeared in less than 5% of the cases. Even fewer people had been known to have abused propoxyphene before their deaths, but 18% of the population had been known to 'self-medicate', using multiple drugs without appropriate medical supervision. The distribution of males to females approximated that of the US population.(ABSTRACT TRUNCATED AT 400 WORDS)