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Re: I hope this covers the topic AntiTrust

Posted by Larry Hoover on September 18, 2004, at 12:00:44

In reply to some please explain this to me!!!!, posted by AntiTrust on September 15, 2004, at 12:43:33

> Why all of a sudden the news has taken off with this antidepressants and teens and suicide??
>
> If teens are at risk for suicide from being on a antidepressant......why would an 'adult' be at LESS risk?? I don't get it...someone explain

The recent media focus on teen suicidality is a political trend, not a scientific one. Frankly, much of it is driven by the church of scientology. And, by fear-mongering in the lay press.

What's lacking, in my opinion, is any link to verification. Anecdote doesn't teach us anything at all. You can't create statistics from individual acts, just as you can't apply statistics to individuals.

What sort of verification is there? One of the most useful, and I believe most credible, forms of verification comes from post-mortem studies on suicides themselves. I can't believe that medical examiners and the like have any vested interest in distorting the evidence they collect. There's not a whole lot of such evidence in the medical literature, but what is there is both consistent, and convincing. Let's start with data collected in adolescent suicides.

Over a five year period, there were 66 adolescent suicides in New York City. Blood was analyzed for antidepressants in 58 of those individuals. In no instances was paroxetine (Paxil) found in the subjects' blood. In only four individuals was *any* antidepressant of any sort identified.(1) That's less than 7% of the subjects.

Utah has the dubious distinction of both having the highest suicide rate in the United States (or very close to it), and the highest proportion of its population on antidepressant medication. It came as a surprise, then, when a study of 49 adolescent suicides determined that *none* had SSRIs in the their blood, despite the fact that 24 percent had been prescribed these antidepressants.(2) That's an astounding rate of non-compliance, in my opinion. And if you were the parent of one those non-compliant children, what conclusion might you reach about the effect of the meds?

It's possible that these two reports may not be representative of the country as a whole. A study covering the decade from 1990-2000, in 588 different locations in the United States, found that antidepressant use in adolescents reduced suicide. They actually developed a mathematical relationship, showing that each percentage increase in antidepressant use led to a reduction in the suicide rate by 0.23 per 100,000 youths.(3) Not only that, but both alpha and beta error estimates were less than .05. I'll leave that point to statisticians, but that suggests that you can really have confidence in the results. In any case, over a nearly identical period of time, the Centres for Disease Control reported that youth suicide rates had declined from 6.2 to 4.6 per 100,000.(4) Applying the formula from reference 3, such a reduction would require an increase in antidepressant use of about 8%. Youth suicide rates are falling, and it may be coincidence, but it is happening during a period when SSRI use is escalating at very high rates.

If antidepressant use is not predictive of adolescent suicide, then what factors are predictive? Other than depression itself, those factors are: interpersonal conflict, sexual and physical abuse, alcohol (in particular), and other substance abuse. But not, apparently, antidepressant use.

A retrospective analysis (looking back at data collected over a period of time) of adolescent suicide attempts and ideation which led to emergency room treatment, interpersonal stress and financial stress were associated with these behaviours. Data were not consistently collected with respect to a history of physical or sexual abuse, but in those cases where the data were collected, about 2/3 had positive histories of abuse.(5)

What about alcohol? Binge drinking is a significant predictor of adolescent suicide.(6) But is depression the cause of binge drinking and suicide, or does drinking drive depression and suicide? The answer seems to depend on gender. Modelling of drinking and suicidal behaviours in an adolescent population showed that suicidality precedes drinking in females, whereas drinking problems precede suicidality in males.(7) In either case, self-medication is an explanatory component of the behaviour. Do we want our children drinking to seek relief, or might antidepressants be a better idea?

What about the rest of us? Again, let's start with post-mortem analyses.

In over 5,000 suicides in Sweden, blood analyses showed that 16.5% had detectable antidepressants in their blood, although epidemiological evidence suggests that up to 85% of suicides are depressed.(8) The same dataset appears to have been reported in a different way, showing gender and age differentials in the use of antidepressants comcommittant with suicide. Men and youth are undertreated, especially.(9) A similar study based on U.S. data (particularly that for Mobile Alabama) found rates (15%) and gender imbalances that seem to be very similar to those findings from Sweden, for a similar period of time.(10)

What about alcohol? I'm not going to belabour the point, as alcohol consumption is well known to be the most significant risk factor for suicide (after depression itself), but here's a sample of the literature. Alcohol was consumed just prior to suicide in between 40-50% of all suicides in Sweden.(11) That's about three times as often as antidepressants.

Still, though, what do we know about the rate of suicide in untreated depressives versus those treated with antidepressants? The fear-mongering literature makes scary comparisons between rates of suicide in antidepressant-treated depressives and *normal* people. But surely, that comparison is like comparing chalk to cheese. What do we know about the relative suicide rates of the depressed population, medicated vs. unmedicated? I can't say it any better than this, from reference 12, "The calculated risk for suicide among depressed patients who were treated with antidepressants was 141 per 100,000 person years and, among the untreated, 259 per 100,000 person years (i.e., 1.8 times higher among the untreated). This supports the hypothesis that antidepressant medication decreases the risk for suicide in depressed patients. The reason this has not been obvious in the general suicide statistics seems to be that so few depressed people are treated with antidepressants."

I do have plans to do a more comprehensive review of the literature, but I thought I'd start with this. I hope it answers the questions satisfactorily.

Lar


REFERENCES:

1. J Clin Psychiatry. 2004 Jul;65(7):915-8.

Paroxetine, other antidepressants, and youth suicide in New York City: 1993 through 1998.

Leon AC, Marzuk PM, Tardiff K, Teres JJ.

Department of Psychiatry, Weill Medical College of Cornell University, New York, NY10021, USA. acleon@med.cornell.edu

BACKGROUND: Regulatory agencies in the United Kingdom and the United States have recently issued warnings about a possible link between suicidal ideation and attempts and the use of paroxetine in a pediatric patient population. The objective of this study was to determine the proportion of youth suicides that tested positive for paroxetine or other antidepressants in medical examiner toxicologic testing in New York City from 1993 through 1998, the first 6 years that paroxetine was available in the United States. METHOD: Subjects in this medical examiner surveillance study were suicides less than 18 years of age. Serum toxicology was examined for paroxetine and other antidepressants. RESULTS: There were 66 suicides among persons under 18 years of age in the years 1993 through 1998. Toxicology was tested in 58 (87.9%) of the 66 suicides, and 54 (81.8%) had injury-death intervals of 3 days or less. None of the victims had paroxetine detected in their blood obtained at the time of autopsy. Imipramine was detected in 2 victims and fluoxetine in another 2. CONCLUSION: Despite regulatory concerns, none of the autopsies of youth suicides in New York City detected paroxetine in the victims, although other antidepressants were detected in 4 victims. However, in the vast majority of the youth suicides, there was no evidence of anti-depressant use immediately prior to death.

2. Gray D, Moskos M, Keller T (2003, April 25). Utah Youth Suicide Study: New Findings. Presented at the annual meeting of the American Association of Suicidology, Sante Fe, New Mexico. As cited in: http://www.acnp.org/exec_summary.pdf

"In a study of 49 adolescent suicides, a research team in Utah recently reported in an abstract that 24 percent had been prescribed antidepressants, but *none* (emphasis in original) tested positive for SSRIs at the time of their death."


3. Arch Gen Psychiatry. 2003 Oct;60(10):978-82.

Relationship between antidepressant medication treatment and suicide in adolescents.

Olfson M, Shaffer D, Marcus SC, Greenberg T.

Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University,

New York 10032, USA. olfsonm@child.cpmc.columbia.edu

CONTEXT: A decade of increasing antidepressant medication treatment for adolescents and corresponding declines in suicide rates raise the possibility that antidepressants have helped prevent youth suicide. OBJECTIVE: To evaluate the relationship between regional changes in antidepressant medication treatment and suicide in adolescents from 1990 to 2000. DESIGN: Analysis of prescription data from the nation's largest pharmacy benefit management organization, national suicide mortality files, regional sociodemographic data from the 1990 and 2000 US Census, and regional data on physicians per capita. PARTICIPANTS: Youth aged 10 to 19 years who filled a prescription for antidepressant medication and same-aged completed suicides from 588 three-digit ZIP code regions in the United States. MAIN OUTCOME MEASURES: The relationship between regional change in antidepressant medication treatment and suicide rate stratified by sex, age group, regional median income, and regional racial composition. RESULTS: There was a significant adjusted negative relationship between regional change in antidepressant medication treatment and suicide during the study period. A 1% increase in adolescent use of antidepressants was associated with a decrease of 0.23 suicide per 100 000 adolescents per year (beta = -.023, t = -5.14, P<.001). In stratified adjusted analyses, significant inverse relationships were present among males (beta = -.032, t = -3.81, P<.001), youth aged 15 to 19 years (beta = -.029, t = -3.43, P<.001), and regions with lower family median incomes (beta = -.023, t = -3.73, P<.001). CONCLUSIONS: An inverse relationship between regional change in use of antidepressants and suicide raises the possibility of a role for using antidepressant treatment in youth suicide prevention efforts, especially for males, older adolescents, and adolescents who reside in lower-income regions.

4. MMWR Morb Mortal Wkly Rep. 2004 Jun 11;53(22):471-4.

Methods of suicide among persons aged 10-19 years--United States, 1992-2001.

Centers for Disease Control and Prevention (CDC).

In 2001, suicide was the third leading cause of death among persons aged 10-19 years. The most common method of suicide in this age group was by firearm (49%), followed by suffocation (mostly hanging) (38%) and poisoning (7%). During 1992-2001, although the overall suicide rate among persons aged 10-19 years declined from 6.2 to 4.6 per 100,000 population, methods of suicide changed substantially. To characterize trends in suicide methods among persons in this age group, CDC analyzed data for persons living in the United States during 1992-2001. This report summarizes the results of that analysis, which indicated a substantial decline in suicides by firearm and an increase in suicides by suffocation in persons aged 10-14 and 15-19 years. Beginning in 1997, among persons aged 10-14 years, suffocation surpassed firearms as the most common suicide method. The decline in firearm suicides combined with the increase in suicides by suffocation suggests that changes have occurred in suicidal behavior among youths during the preceding decade. Public health officials should develop intervention strategies that address the challenges posed by these changes, including programs that integrate monitoring systems, etiologic research, and comprehensive prevention activities.

5. Int J Adolesc Med Health. 2002 Jan-Mar;14(1):55-60.

Retrospective analysis of youth evaluated for suicide attempt or suicidal ideation in an emergency room setting.

Hagedorn J, Omar H.

Section of Adolescent Medicine, Department of Pediatrics, University of Kentucky, Lexington, USA.

Suicide is the third leading cause of death in adolescents and a major contributor to morbidity in this age group. The objective of this study was to look at the demographics, major stressors and factors leading to attempting suicide as well as the methods of attempted suicide in adolescents admitted to two hospitals in a medium size city. Medical records were reviewed of adolescents admitted to two area hospitals for attempted suicide between 7/1/97-12/31/99. Coroner's data on completed suicide were also reviewed. In the study period a total of 287 persons aged 21 years or under were admitted for attempted suicide. Mean age was 16.9 years (range 7-21). 53.4% of the total were females and 46.6 were males with the majority of the total being Caucasians (75.6%). Interpersonal conflicts were the most common stressors preceding the attempt; fight with parents 20%, end of a relationship 12%, fight with a significant other 8%. Financial difficulties were the culprit in 10% of the cases. Abuse was not clearly recorded in 64% of cases. In cases where documentation was clear, 60% reported sexual and 67% physical abuse. Nearly half of the patients had a prior psychiatric diagnosis with prior suicide attempt and depression being most common at 27 and 18% respectively. Overdose was the most common method utilized. There were 20 completed adolescent suicides in the area with firearms as the method used in all of them. It is concluded that suicide continues to be a major problem in adolescents. Access to guns may be a detrimental factor in completing suicide. Health care providers may help identify those at risk by routinely screening all adolescents for depression and suicide.

6. Alcohol Clin Exp Res. 2004 May;28(5 Suppl):29S-37S.

Suicidal behaviors and alcohol use among adolescents: a developmental psychopathology perspective.

Windle M.

Center for the Advancement of Youth Health, University of Alabama at Birmingham, Birmingham, Alabama, USA. windle@uab.edu

A developmental psychopathology conceptual model was provided to represent the major categories of risk and protective factors, including alcohol use and binge drinking, that predict suicidal behaviors that range from suicidal thoughts to completed suicides. The conceptual model emphasized the importance of identifying age-specific sets of risk and protective factors to facilitate the development of effective interventions. As an empirical illustration, a multivariate mediation path model was specified and evaluated with a sample of teens. Findings indicated that several distal variables (e.g., difficult temperament, coping motives for drinking, lower family support, higher percentage of friends using alcohol) significantly predicted mediators (e.g., depression, stressful events, binge drinking) that, in turn, predicted suicidal behaviors. Binge drinking significantly predicted suicide attempts over and above the influence of depression and stressful events.


7. Addict Behav. 2003 Jun;28(4):705-24.

Adolescent alcohol use and suicidal ideation: a nonrecursive model.

Light JM, Grube JW, Madden PA, Gover J.

Prevention Research Center, 2150 Shattuck Avenue, Suite 900, Berkeley, CA 94704, USA. jlight@prev.org

Prior research has found that adolescent alcohol use is correlated with suicide ideation and behaviors. The causal nature of this relationship, however, has not been established. It could result from a significant causal effect in either direction, both directions, or joint influence from some third factor. These possibilities were addressed using data from a two-wave (24-month) panel survey of junior and senior high school students aged 12 or older at Wave 1. A total of 615 students (301 males, 314 females) completed both waves. Alcohol Problems were related to suicide ideation and behavior cross-sectionally within Waves 1 and 2. Separate Full-Information Maximum Likelihood (FIML) models were estimated for males and females using the same set of identifying restrictions. Results suggested that suicidality leads to increased alcohol-related problems for females, while alcohol-related problems are predictive of suicidality among males. Sensitivity and spuriousness tests did not appreciably alter this conclusion.

8. Acta Psychiatr Scand. 1997 Aug;96(2):94-100.

The utilization of antidepressants--a key issue in the prevention of suicide: an analysis of 5281 suicides in Sweden during the period 1992-1994.

Isacsson G, Holmgren P, Druid H, Bergman U.

Department of Clinical Neurosciences and Family Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.

Antidepressants detected by the National Department of Forensic Chemistry in 5281 suicides in Sweden during the period 1992-1994 were related to data on usage expressed in person-years of exposure. Antidepressants were detected in 874 subjects (16.5%). In relation to their use, fluvoxamine, citalopram, moclobemide, mianserin and trimipramine were found more often than the reference drug, amitriptyline (i.e. over-risks). Toxic concentrations of antidepressants were detected in 232 subjects (4.4%). Most people committing suicide were not taking antidepressants immediately before their death, even though 40-85% may have been depressed. Undertreatment and therapeutic failure are the main problems with antidepressants, not the risk of using antidepressants in overdose. Comparisons of new antidepressants should focus on efficacy in relation to reference tricyclics. The huge increase in the use of antidepressants in Sweden since 1990-1991 has been paralleled by a significant decrease in suicide rates.

9. Br J Psychiatry. 1999 Mar;174:259-65.

Comment in:
Br J Psychiatry. 1999 Jul;175:90-1.

Psychotropics and suicide prevention. Implications from toxicological screening of 5281 suicides in Sweden 1992-1994.

Isacsson G, Holmgren P, Druid H, Bergman U.

Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Sweden. Goran.Isacsson@cnsf.ki.se

BACKGROUND: Systematic clinical investigations of consecutive suicides have found psychiatric disorders in 90-95% of subjects (depressive disorder 30-87%). AIMS: To investigate use of psychotropics in men and women of different ages who commit suicide. METHOD: Results of toxicological screening in 5281 suicides in Sweden 1992-94 were studied. RESULTS: Psychotropics were detected in 45.3% of the suicides. Antidepressants were detected in 12.4% of the men and 26.2% of the women (7.2% and 14.2%, respectively, of those under 30 years of age). Neuroleptics or antiepileptics (in the absence of antidepressants) were detected in 8.3%, and anxiolytics/hypnotics alone in 20.5% of the subjects. Overdose by an antidepressant was the probable cause of death in 2.1% of the men and 7.9% of the women. CONCLUSIONS: The pattern of psychotropics detected in toxicology was incongruent with the pattern of diagnoses found in the clinical investigations of suicides mentioned above. Depression appears to be under treated in individuals committing suicide, especially in men and in subjects under 30 years of age.

10. J Affect Disord. 1997 Sep;45(3):135-42.

Suicide and antidepressants in south Alabama: evidence for improved treatment of depression.

Rich CL, Isacsson G.

Department of Psychiatry, University of South Alabama, Mobile, USA.

The purpose of this study was to investigate the occurrence of antidepressants among suicides in the era since the introduction of newer less toxic antidepressants. Comprehensive post mortem toxicological examinations were performed on 94% of certain and uncertain suicides in Mobile County, Alabama, between October 1, 1990 and September 30, 1995. Comparisons were made between current data from Mobile and data from the San Diego study in 1981-83. About twice as many suicides in Mobile were positive for antidepressants than in San Diego (15% vs. 8%). The proportions of antidepressant overdose deaths were the same (5%), however. Antidepressants were found in significantly fewer males than females and blacks than whites in Mobile. Although antidepressants were found in a greater proportion of people who committed suicide in Mobile, they were not used more frequently as a means of suicide. The authors conclude that this may represent improvement in care received by people with depression. It remains to be determined what suicide preventive effects individual antidepressants or groups of antidepressants may have.

11. Forensic Sci Int. 1996 Apr 2;78(2):157-63.

Pathoanatomic findings and blood alcohol analysis at autopsy (BAC) in forensic diagnoses of undetermined suicide. A cross-cultural study.

Ferrada-Noli M, Ormstad K, Asberg M.

Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.

In Sweden, ca. 25% of unnatural deaths ascribed to self-inflicted injury are finally recorded as 'undetermined suicide' (abbreviated UMSA), i.e. the forensic pathologist has not been able to establish whether the fatality was an accident or a suicide. In the present study, a series of UMSA cases was investigated with the aims to study the impact of immigrant status, and alcohol abuse on the occurrence of this forensic diagnosis on the mode of death. The alcohol issue was addressed by focusing on blood alcohol concentrations at autopsy (BAC) and post mortem signs of alcohol-related organ pathology. The results can be summarised as follows: Positive BAC occurred at an equal rate in the UMSA group and in definite suicides, i.e. about 45%. Among non-Swedish UMSA victims positive BAC was more common (50%) than among the Swedish (41%), whereas no difference was found in the definite suicide group. The level of BAC at autopsy was significantly higher in Finnish immigrants than in other ethnic groups. Organic signs of chronic alcohol abuse were found in 13 of 40 cases testing positive for BAC; thus, presence of alcohol at autopsy may reflect incidental intake rather than habitual overconsumption.

12. J Affect Disord. 1996 Nov 4;41(1):1-8.

Epidemiological data suggest antidepressants reduce suicide risk among depressives.

Isacsson G, Bergman U, Rich CL.

Department of Clinical Neuroscience and Family Medicine, Division of Psychiatry, Karolinska Institute, Huddinge University Hospital, Sweden. goran.isacsson.@cnsf.ki.se

In spite of the availability of antidepressant medication for several decades, it has not been shown that such medication lowers the risk for suicide in depressed patients. This report explores this apparent paradox by means of pharmacoepidemiological methods. Data on the prevalence of depression in the population and among suicides as well as data on the prevalence of antidepressant medication in depressed suicides were obtained from a review of the literature. Data on the prevalence of antidepressant medication in the population in 1990-1991 were obtained from the statistics of the Swedish National Corporation of Pharmacies. It was found that only one in five depressed individuals with major depression were treated with antidepressants in Sweden. The calculated risk for suicide among depressed patients who were treated with antidepressants was 141 per 100,000 person years and, among the untreated, 259 per 100,000 person years (i.e., 1.8 times higher among the untreated). This supports the hypothesis that antidepressant medication decreases the risk for suicide in depressed patients. The reason this has not been obvious in the general suicide statistics seems to be that so few depressed people are treated with antidepressants. Effective suicide prevention strategies should include intensive efforts to recognize and treat more depressed people.

 

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