Alan D. Dean

Antidepressants and suicide

Abstract Objective: To estimate the rate and means of suicide among people taking 10 commonly prescribed antidepressant drugs: dothiepin, amitriptyline, clomipramine, imipramine, flupenthixol, lofepramine, mianserin, fluoxetine, doxepin, and trazodone. Design: Open cohort study with a nested casecontrol analysis. Setting: General practices in the United Kingdom that used VAMP computers to maintain their patient records from January 1988 to February 1993. Subjects: 172598 people who had at least one prescription for one of the 10 antidepresssants during the study period. Main outcome measure: Suicide confirmed by general practitioner or on death certificate, or both. Results: 143 people committed suicide. The overall rate of suicide was estimated to be 8.5 per 10000 person years (95% confidence interval 7.2 to 10.0). Rates of suicide were higher in men than women (relative risk 2.8 (95% confidence interval 1.9 to 4.0)), people with a history of feeling suicidal (19.2 (9.5 to 38.7)), and people who had taken several different antidepressants (2.8 (1.8 to 4.3)). People who received high doses of antidepressants and those who had had a prescription in the 30 days before they committed suicide were also at higher risk than those who had received low doses and had had their prescriptions 30 or more days previously (2.3 (1.4 to 3.7) and 2.3 (1.6 to 3.4)) respectively. Rates of suicide were higher in patients who received fluoxetine, but this may be explained by selection biases which were present for those drug users. Conclusion: Several factors correlate with the risk of suicide in people taking antidepressants. After controlling for these factors, the risk of suicide was similar among the 10 study antidepressants. Overdose with antidepressants accounted for only 14% of the suicides. Key messages Key messages As in previous studies, more men than women committed suicide People with a history of suicidal behaviour were at a greatly increased risk of committing suicide People who had received their last antidepressant prescription in the previous 30 days were more likely to commit suicide than those who had received their last antidepressant 30 or more days previously The risk of suicide was not determined by the antidepressant prescribed

Urinary tract infections and estrogen use in older women

To examine the relationship between exogenous estrogen use and risk of clinically diagnosed urinary tract infection (UTI) in older women.

The risk of sulfasalazine- and mesalazine-associated blood disorders.

Sulfasalazine (SASP) has often been reported to cause serious blood disorders, particularly agranulocytosis; however, little quantitative information is available to estimate the risk or to identify possible modifiers of the risk. We used comprehensive clinical information recorded on office computers by selected general practitioners in Britain to conduct a follow‐up study of some 10,000 users of SASP and some 4000 users of mesalazine to estimate the risk of blood disorders associated with these drugs. Overall, the frequency of blood disorders attributable to SASP was 27/10,332 (2.6/1000 users). The risk for SASP users who were treated for arthritic disorders (6.1/1000 users) was some 10 times higher than that for users who were treated for inflammatory bowel disease (0.6/1000 users). There were no cases of blood disorders in users of mesalazine.

Antidepressant drugs and suicide.

The current study provides estimated rates of suicide among users of antidepressant drugs. The data were derived from two population-based data resources: United Kingdom general practitioners using computers provided by Value Added Medical Products, Ltd., and Group Health Cooperative of Puget Sound. The results apply specifically to these populations. The overall rates of suicide in ever users of the study drugs usually used to treat depression were 6.5 x 10(-4) person-years in persons present in the U.K. resource and 5.1 x 10(-4) person-years in members of The Puget Sound group. Rates of suicide among users of particular antidepressant drugs varied somewhat, but the rates were consistent with biologic variability, with the possible exception of rates for mianserin (based on 4 exposed cases), which were higher than rates for other antidepressants. Consistent findings were (1) suicide rates are substantially higher in men than in women, and (2) the use of firearms as a mode of suicide is common in the northwest United States and uncommon in the United Kingdom.

Liver Disease Associated With Diclofenac, Naproxen, and Piroxicam

Based on information derived from computers used by general practitioners in the United Kingdom, we identified all patients with any recorded diagnosis of a liver disorder within 90 days of a prior prescription for diclofenac, naproxen, or piroxicam, three nonsteroidal antiinflammatory drugs (NSAIDs). The follow‐up cohort consisted of 102,644 persons who used one or more of these drugs. A case history was requested from the physician to provide a description of the liver disorder and its relation to NSAID exposure. One case of clinically important liver disease was likely to have been caused by a study drug and another appeared to be caused by use of numerous NSAIDs. In 10 additional patients a causal connection between a study NSAID and the liver disorder seemed unlikely but could not be fully ruled out. We conclude that serious liver disease caused by diclofenac, naproxen, or piroxicam appears to be uncommon.

Liver Disorders in Patients Receiving Chlorpromazine or Isoniazid

Based on information derived from computers and clinical records obtained from general practitioners in the United Kingdom, we estimated the frequency of liver toxicity associated with two known hepatotoxins, chlorpromazine and isoniazid. Among the cohort of 10,502 users of chlorpromazine, 14 had illnesses compatible with drug‐induced liver disease, a frequency of 1.3/1000 users (95% CI 0.8, 2.2). Four presumed cases of the disorder occurred among 921 users of isoniazid, for a frequency of 4/1000 users (95% CI 1.7, 11.1). This study provides population‐based quantification of the frequency of liver disorders associated with the use of these two agents.

Antidepressants and convulsions.

We reviewed available computer records and clinical charts in an estimated 42,000 recipients of antidepressant drugs. The study was restricted to persons with no known condition predisposing to convulsions. Only 16 study subjects developed a convulsive disorder that we judged could have been caused by an antidepressant. We conclude that the frequency of convulsions caused by these drugs used at usual prescribed doses in the settings studied is substantially less than one per 1,000 recipients who have no conditions predisposing to convulsions.

Nonsteroidal Antiinflammatory Drugs and Certain Rare, Serious Adverse Events: A Cohort Study

We performed a population‐based study of over 100,000 users of diclofenac, naproxen, or piroxicam to identify cases of important blood, skin, central nervous system, kidney, pancreas, or pulmonary disorders caused by these drugs. In three cases a causal relation seemed likely; one of hemolytic anemia attributed to diclofenac, one of neutropenia attributed to naproxen, and one of pancreatitis attributed to piroxicam. In 13 additional cases a causal connection seemed unlikely but could not be fully ruled out. We conclude that such illnesses are uncommonly caused by the three agents studied.

A Comparison of the Risk of Hypoglycemia Between Users of Human and Animal Insulins. 1. Experience in the United Kingdom

In a case‐control study of 121 young insulin‐dependent diabetics diagnosed as having an episode of hypoglycemia, the relative risk estimate comparing human with animal insulins was 0.8 (95% confidence interval 0.4, 1.6) controlling for age, general practice, and calendar time. We conclude that in this study population derived from general practices in the United Kingdom, the risk of hypoglycemia was no higher in users of human insulin than it was in users of animal insulins.