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Drugs associated with more suicidal ideations are also associated with more suicide attempts.

Robertson HT, Allison DB - PLoS ONE (2009)

Bottom Line: Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics, University of Alabama at Birmingham, Ryals School of Public Health, Birmingham, Alabama, United States of America.

ABSTRACT

Context: In randomized controlled trials (RCTs), some drugs, including CB1 antagonists for obesity treatment, have been shown to cause increased suicidal ideation. A key question is whether drugs that increase or are associated with increased suicidal ideations are also associated with suicidal behavior, or whether drug-induced suicidal ideations are unlinked epiphenomena that do not presage the more troubling and potentially irrevocable outcome of suicidal behavior. This is difficult to determine in RCTs because of the rarity of suicidal attempts and completions.

Objective: To determine whether drugs associated with more suicidal ideations are also associated with more suicide attempts in large spontaneous adverse event (AE) report databases.

Methodology: Generalized linear models with negative binomial distribution were fitted to Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (AERS) data from 2004 to 2008. A total of 1,404,470 AEs from 832 drugs were analyzed as a function of reports of suicidal ideations; other non-suicidal adverse reactions; drug class; proportion of reports from males; and average age of subject for which AE was filed. Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.

Main outcome measures: Reported suicide attempts and completed suicides per drug.

Results: 832 drugs, ranging from abacavir to zopiclone, were evaluated. The 832 drugs, as primary suspect drugs in a given adverse event, accounted for over 99.9% of recorded AERS. Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.

Conclusions: In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions. This association suggests that drug-induced suicidal ideations observed in RCTs plausibly represent harbingers that presage the more serious suicide attempts and completions and should be a cause for concern.

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Related in: MedlinePlus

Distribution of suicide attempts per drug.
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pone-0007312-g002: Distribution of suicide attempts per drug.

Mentions: The distribution of reported suicide attempts per drug was highly positively skewed (Figure 2). That is, 690 out of 832 drugs (83%) had fewer than 10 attempts reported during this 4-year time period, while there was a long tail of drugs with 10 or more suicide attempts. The median number of attempts was 0 attempts per drug, while its SD was 84 (Table 3). On the high end, there were up to 1,323 suicide attempts out of 27,012 AERs (4.9%) for paroxetine. Suicide ideations followed a similar positively skewed distribution, with a median of 0 reported ideations per drug (SD = 57.5). On average, there were more attempts reported than ideations, although there were 135 drugs (16.2% of drugs) where the number of reported ideations was greater than attempts. Suicidal ideation would be expected to be considerably more common than suicidal acts, so there appears to be reporting bias here; the less serious outcomes appeared to be reported less often. Overall, suicide attempts and ideations were positively correlated (r = +.69, p<.0001); the strength of the correlation was stronger than that between suicide attempts and non-suicidal AERs (r = +.29, p<.0001). The positive association remained after adjusting for non-suicidal AERs and other variables in multiple regression models.


Drugs associated with more suicidal ideations are also associated with more suicide attempts.

Robertson HT, Allison DB - PLoS ONE (2009)

Distribution of suicide attempts per drug.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2749439&req=5

pone-0007312-g002: Distribution of suicide attempts per drug.
Mentions: The distribution of reported suicide attempts per drug was highly positively skewed (Figure 2). That is, 690 out of 832 drugs (83%) had fewer than 10 attempts reported during this 4-year time period, while there was a long tail of drugs with 10 or more suicide attempts. The median number of attempts was 0 attempts per drug, while its SD was 84 (Table 3). On the high end, there were up to 1,323 suicide attempts out of 27,012 AERs (4.9%) for paroxetine. Suicide ideations followed a similar positively skewed distribution, with a median of 0 reported ideations per drug (SD = 57.5). On average, there were more attempts reported than ideations, although there were 135 drugs (16.2% of drugs) where the number of reported ideations was greater than attempts. Suicidal ideation would be expected to be considerably more common than suicidal acts, so there appears to be reporting bias here; the less serious outcomes appeared to be reported less often. Overall, suicide attempts and ideations were positively correlated (r = +.69, p<.0001); the strength of the correlation was stronger than that between suicide attempts and non-suicidal AERs (r = +.29, p<.0001). The positive association remained after adjusting for non-suicidal AERs and other variables in multiple regression models.

Bottom Line: Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics, University of Alabama at Birmingham, Ryals School of Public Health, Birmingham, Alabama, United States of America.

ABSTRACT

Context: In randomized controlled trials (RCTs), some drugs, including CB1 antagonists for obesity treatment, have been shown to cause increased suicidal ideation. A key question is whether drugs that increase or are associated with increased suicidal ideations are also associated with suicidal behavior, or whether drug-induced suicidal ideations are unlinked epiphenomena that do not presage the more troubling and potentially irrevocable outcome of suicidal behavior. This is difficult to determine in RCTs because of the rarity of suicidal attempts and completions.

Objective: To determine whether drugs associated with more suicidal ideations are also associated with more suicide attempts in large spontaneous adverse event (AE) report databases.

Methodology: Generalized linear models with negative binomial distribution were fitted to Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (AERS) data from 2004 to 2008. A total of 1,404,470 AEs from 832 drugs were analyzed as a function of reports of suicidal ideations; other non-suicidal adverse reactions; drug class; proportion of reports from males; and average age of subject for which AE was filed. Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.

Main outcome measures: Reported suicide attempts and completed suicides per drug.

Results: 832 drugs, ranging from abacavir to zopiclone, were evaluated. The 832 drugs, as primary suspect drugs in a given adverse event, accounted for over 99.9% of recorded AERS. Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.

Conclusions: In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions. This association suggests that drug-induced suicidal ideations observed in RCTs plausibly represent harbingers that presage the more serious suicide attempts and completions and should be a cause for concern.

Show MeSH
Related in: MedlinePlus