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Friday 1 October 2010

newer antidepressants, citalopram, venlafaxine, and mirtazapine are potentially the most lethal in overdose (Br J Psychiatry. 2010;196:354-358).

newer antidepressants, citalopram, venlafaxine, and mirtazapine are potentially the most lethal in overdose (Br J Psychiatry. 2010;196:354-358).




http://www.medscape.com/viewarticle/729452





Prescription and Nonprescription Medications Implicated in Overdose Suicides

Kate Johnson



September 27, 2010 (Toronto, Ontario) — Psychotropic and other prescription drugs, as well as over-the-counter medications, are frequently used in overdose suicides, according to preliminary findings from a study reported at here at the Canadian Psychiatric Association 60th Annual Conference.



"The key point is that physicians prescribing certain classes of medications should be extravigilant if a patient is depressed or suicidal," said Mark Sinyor, MD, a fourth-year resident at the Department of Psychiatry, University of Toronto in Ontario, Canada.



A medical record review revealed 397 overdose suicides in Toronto during a 10-year period (1998-2007), which were divided evenly between men and women.



Medical examiner reports showed that pain killers, most commonly opioids, either alone or in combination with other drugs, were implicated in almost one-third (n = 112) of these suicides.



The second most common class of drugs was sedative hypnotics/benzodiazepines, which were implicated, either alone or in combination, in 105 cases.



Over-the-counter medications were the third most common source of overdose (n = 85), in particular diphenhydramine.



Tricyclic antidepressants came fourth on the list, either alone or in combination with other drugs (n = 81), with amitriptyline being the most common choice.



Newer Antidepressants Possibly the Most Lethal



In 10 cases, the only drug considered to be present in a lethal amount was a newer antidepressant," said Dr. Sinyor, noting a recent study showing that of the selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants, citalopram, venlafaxine, and mirtazapine are potentially the most lethal in overdose (Br J Psychiatry. 2010;196:354-358).



"In 7 of the 10 cases at least one of those drugs was present," he added.



Most suicides occurred in 40- to 59-year-olds, with 50% of all male and 45% of all female suicides falling into this age group.



This supports 2007 data from the US National Violent Deaths Reporting study that found the highest rate for suicide in 45- to 54-year-olds.



The most common psychiatric diagnoses in the cohort included major depressive disorder, substance abuse disorders, bipolar disorder, and schizophrenia.



However, all diagnoses, including others such as anxiety disorders and personality disorders, were most likely underreported, said co–lead investigator Andrew Howlett, MD, also a fourth-year resident at the University of Toronto.



"There was very little evidence in the charts [about diagnoses], but compared to previous research, we think these other diagnoses were underreported," he added.



Most suicides occurred in people who were unmarried (79%) and who overdosed at home (71%).



Forty-three percent of the cohort had medical conditions (unspecified), 42% had made a previous suicide attempt, and only 38% had left a suicide note.



Important Reminder



Predictors for overdose with specific psychotropic medications were not obvious. However, individuals with a general medical condition were twice as likely to overdose with nonpsychotropic medications compared with healthy individuals.



For over-the-counter overdose, predictive factors were being unmarried (odds ratio, 3.1; P < .01) and no previous suicide attempts (odds ratio, 2.7; P < .01).



"What's kind of interesting is that if they had a prior suicide attempt they were less likely to leave a note [P < .01]," said Dr. Sinyor. He noted that with almost two-thirds (62%) not leaving a suicide note and a large percentage (42%) with a history of suicide attempts, many cases are suggestive of chronic impulsivity.



"It seems like a large percentage of these were impulsive acts. It wasn't part of our research, but reading through the charts there were tons of personal crises, often relationships breaking up, that tended to precede the overdose.



"I certainly think it's a reminder to those of us prescribing psychotropic medications," said session moderator Jennifer Brasch, MD, medical director of Psychiatric Emergency Services at St. Joseph's Healthcare and associate professor in the Department of Psychiatry and Behavioral Neurosciences at McMaster University in Hamilton, Ontario, Canada.



"There are so many different medications in involved in the use of overdose. Tricyclics are well known to be highly toxic, but there were a number of SSRIs implicated in deaths by overdose, and it's a reminder to healthcare providers to be cautious in prescribing and to limit the number of pills that a patient has available."



In addition to awareness about prescribing medications, physicians should also note that a significant number of suicides involved diphenhydramine, added Dr. Sinyor.



"Diphenhydramine is the active ingredient in Benadryl, but it's also the active ingredient in SleepEze and Nytol and the newer sleep supplements. Diphenhydramine is a readily available drug that is now frequently used for overdose — at least in Toronto."



Dr. Brasch has disclosed no relevant financial relationships. Dr. Sinyor, Dr. Howlett, and Dr. Cheung have disclosed no relevant financial relationships and no funding for the trial; however, one of their coinvestigators (Dr. Ayal Schaffer) provided the following disclosure statements for previous research: Advisory Board: AstraZeneca Canada Inc, Bristol-Myers Squibb Inc, and Eli Lilly Canada Inc; Clinical Trials or Studies: AstraZeneca Canada Inc, Brain Cells Inc, and Servier Canada; Honoraria or Other Fees: AstraZeneca Canada Inc, Bristol-Myers Squibb Inc, Eli Lilly Canada Inc, Lundbeck Canada Inc, and Pfizer Canada Inc; Research Grants: AstraZeneca Canada Inc, BrainCells Inc, and Servier Canada.



Canadian Psychiatric Association (CPA) 60th Annual Conference: Abstract PS1d. Presented September 23, 2010.

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