Suicide Risk Tied to Acne Severity, Not Treatment : Study on association between isotretinoin use, suicidal behavior focuses on timing of treatment.

A large, retrospective cohort study is the latest to look at the association between isotretinoin and attempted suicide. Concerns about a link between isotretinoin and suicidal behavior have abounded for years, although previous studies have failed to show a conclusive link.

By studying when (before, during, or up to 15 years after treatment) suicidal behavior is most likely to occur in relation to treatment, researchers found that although the risk is increased during and up to 1 year after treatment, such risk is more likely related to the psychological effects associated with the disease – severe acne – than with the isotretinoin, and may be affected by treatment failure.

Pharmacoepidemiologist Anders Sundström of the Karolinska Institute in Stockholm and colleagues examined named records for 5,756 Swedish patients (aged 15–49 years) who were prescribed isotretinoin in 1980–1989. The men had a mean age of 22.3 years (women, 27.1 years) at first prescription, and were taking mean daily doses of 44.5 mg and 39.2 mg isotretinoin, respectively, for severe acne. Mean length of treatment was 4 months for men and 3.9 months for women. The patients' clinical records were compared with hospital-discharge and cause-of-death registers for the 1980–2001 period.

In all, 128 patients in the cohort were hospitalized for attempted suicide on 210 occasions during the study period; there were 24 completed suicides during this time. When the study cohort was compared with the general population, the standardized incidence ratios for suicide attempts rose from 0.89 (95% confidence interval, 0.54–1.37) at 3 years before treatment to 1.36 (95% CI, 0.65–2.50) in the year before treatment for first attempts, and from 0.99 (95% CI, 0.65–1.44) at 3 years before treatment to 1.57 (95% CI, 0.86–2.63) in the year before treatment for all attempts.

The risks were shown to be highest within 6 months after the start of treatment: 1.93 (95% CI, 1.08–3.18) for first attempts and 1.78 (95% CI, 1.04–2.85) for all attempts. The investigators also found that women who made suicide attempts received two or three treatments more often than did women who did not attempt suicide, suggesting treatment failure as a possible contributor.

After treatment, the standardized incidence ratio declined to 0.97 (95% CI, 0.64–1.40) for first attempts and 1.04 (95% CI, 0.74–1.43) for all attempts within 3 years. After 3 years and for the duration of follow-up, the rate remained on par with the background rate for the population.

The investigators concluded that “an increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin.” However, they wrote, “the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established.” Patients with a history of suicide attempts need not be denied treatment with isotretinoin, they wrote, but “close monitoring of patients for suicidal behavior for up to a year after treatment has ended” would be advisable (BMJ 2010 Nov. 12 [doi:10/1136/bmj.c5812]).

The investigators acknowledged some limitations of their study, including a lack of data on potential confounding factors other than age, sex, and calendar year. Low statistical precision was also a limitation: Although standardized incidence ratios were clearly rising before treatment, they wrote, “we found no statistical significance until six months after treatment. In the internal cohort crossover analysis – that is, analyzing outcomes before and after treatment in the same population – the differences in incidence did not reach statistical significance, making the estimated number needed to harm uncertain.”

Also, they wrote, “we had no information on the effect of treatment. A bias would exist if the patients who made suicide attempts had a poorer effect of treatment than did those who did not make such attempts. In that case, the suicidal behavior should be attributed to the treatment resistant acne and not to the treatment. However, such bias would only strengthen the assumed association between severe acne and suicidal behavior.”

In an editorial comment, Dr. Parker Magin of the University of Newcastle in Callaghan, New South Wales, Australia, and Dr. John Sullivan of the University of New South Wales in Sydney, said that clinicians could draw important practical conclusions from the study – namely, that during and after treatment with isotretinoin (and especially when treatment is unsuccessful), “patients should be carefully monitored for depression and suicidal thoughts. Patients probably have an increased risk before treatment, however, so all patients with acne of a severity for which isotretinoin is indicated should have psychosocial factors and suicidal intent monitored.”

As for who should perform the monitoring, Dr. Magin said that although dermatologists generally take on that role, general practitioners “have more appropriate training and experience in psychological medicine … and could add invaluable expertise in the psychological aspects of management in a shared care model with dermatologists.” Families of patients, Dr. Magin added, may also help with monitoring. (BMJ 2010 Nov. 12 [doi:10.1136/bmj.c5866])

The study was funded by the Swedish Research Council. Mr. Sundström and his coauthors declared that they had no conflicts of interest. Dr. Magin and Dr. Sullivan have been members of All About Acne, an organization supported by unrestricted educational grants from drug companies. Neither Dr. Magin nor Dr. Sullivan received payment from the organization, and the drug companies that provide support do not manufacture isotretinoin.

A large, retrospective cohort study is the latest to look at the association between isotretinoin and attempted suicide. Concerns about a link between isotretinoin and suicidal behavior have abounded for years, although previous studies have failed to show a conclusive link.

By studying when (before, during, or up to 15 years after treatment) suicidal behavior is most likely to occur in relation to treatment, researchers found that although the risk is increased during and up to 1 year after treatment, such risk is more likely related to the psychological effects associated with the disease – severe acne – than with the isotretinoin, and may be affected by treatment failure.

Pharmacoepidemiologist Anders Sundström of the Karolinska Institute in Stockholm and colleagues examined named records for 5,756 Swedish patients (aged 15–49 years) who were prescribed isotretinoin in 1980–1989. The men had a mean age of 22.3 years (women, 27.1 years) at first prescription, and were taking mean daily doses of 44.5 mg and 39.2 mg isotretinoin, respectively, for severe acne. Mean length of treatment was 4 months for men and 3.9 months for women. The patients' clinical records were compared with hospital-discharge and cause-of-death registers for the 1980–2001 period.

In all, 128 patients in the cohort were hospitalized for attempted suicide on 210 occasions during the study period; there were 24 completed suicides during this time. When the study cohort was compared with the general population, the standardized incidence ratios for suicide attempts rose from 0.89 (95% confidence interval, 0.54–1.37) at 3 years before treatment to 1.36 (95% CI, 0.65–2.50) in the year before treatment for first attempts, and from 0.99 (95% CI, 0.65–1.44) at 3 years before treatment to 1.57 (95% CI, 0.86–2.63) in the year before treatment for all attempts.

The risks were shown to be highest within 6 months after the start of treatment: 1.93 (95% CI, 1.08–3.18) for first attempts and 1.78 (95% CI, 1.04–2.85) for all attempts. The investigators also found that women who made suicide attempts received two or three treatments more often than did women who did not attempt suicide, suggesting treatment failure as a possible contributor.

After treatment, the standardized incidence ratio declined to 0.97 (95% CI, 0.64–1.40) for first attempts and 1.04 (95% CI, 0.74–1.43) for all attempts within 3 years. After 3 years and for the duration of follow-up, the rate remained on par with the background rate for the population.

The investigators concluded that “an increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin.” However, they wrote, “the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established.” Patients with a history of suicide attempts need not be denied treatment with isotretinoin, they wrote, but “close monitoring of patients for suicidal behavior for up to a year after treatment has ended” would be advisable (BMJ 2010 Nov. 12 [doi:10/1136/bmj.c5812]).

The investigators acknowledged some limitations of their study, including a lack of data on potential confounding factors other than age, sex, and calendar year. Low statistical precision was also a limitation: Although standardized incidence ratios were clearly rising before treatment, they wrote, “we found no statistical significance until six months after treatment. In the internal cohort crossover analysis – that is, analyzing outcomes before and after treatment in the same population – the differences in incidence did not reach statistical significance, making the estimated number needed to harm uncertain.”

Also, they wrote, “we had no information on the effect of treatment. A bias would exist if the patients who made suicide attempts had a poorer effect of treatment than did those who did not make such attempts. In that case, the suicidal behavior should be attributed to the treatment resistant acne and not to the treatment. However, such bias would only strengthen the assumed association between severe acne and suicidal behavior.”

In an editorial comment, Dr. Parker Magin of the University of Newcastle in Callaghan, New South Wales, Australia, and Dr. John Sullivan of the University of New South Wales in Sydney, said that clinicians could draw important practical conclusions from the study – namely, that during and after treatment with isotretinoin (and especially when treatment is unsuccessful), “patients should be carefully monitored for depression and suicidal thoughts. Patients probably have an increased risk before treatment, however, so all patients with acne of a severity for which isotretinoin is indicated should have psychosocial factors and suicidal intent monitored.”

As for who should perform the monitoring, Dr. Magin said that although dermatologists generally take on that role, general practitioners “have more appropriate training and experience in psychological medicine … and could add invaluable expertise in the psychological aspects of management in a shared care model with dermatologists.” Families of patients, Dr. Magin added, may also help with monitoring. (BMJ 2010 Nov. 12 [doi:10.1136/bmj.c5866])

The study was funded by the Swedish Research Council. Mr. Sundström and his coauthors declared that they had no conflicts of interest. Dr. Magin and Dr. Sullivan have been members of All About Acne, an organization supported by unrestricted educational grants from drug companies. Neither Dr. Magin nor Dr. Sullivan received payment from the organization, and the drug companies that provide support do not manufacture isotretinoin.

A large, retrospective cohort study is the latest to look at the association between isotretinoin and attempted suicide. Concerns about a link between isotretinoin and suicidal behavior have abounded for years, although previous studies have failed to show a conclusive link.

By studying when (before, during, or up to 15 years after treatment) suicidal behavior is most likely to occur in relation to treatment, researchers found that although the risk is increased during and up to 1 year after treatment, such risk is more likely related to the psychological effects associated with the disease – severe acne – than with the isotretinoin, and may be affected by treatment failure.

Pharmacoepidemiologist Anders Sundström of the Karolinska Institute in Stockholm and colleagues examined named records for 5,756 Swedish patients (aged 15–49 years) who were prescribed isotretinoin in 1980–1989. The men had a mean age of 22.3 years (women, 27.1 years) at first prescription, and were taking mean daily doses of 44.5 mg and 39.2 mg isotretinoin, respectively, for severe acne. Mean length of treatment was 4 months for men and 3.9 months for women. The patients' clinical records were compared with hospital-discharge and cause-of-death registers for the 1980–2001 period.

In all, 128 patients in the cohort were hospitalized for attempted suicide on 210 occasions during the study period; there were 24 completed suicides during this time. When the study cohort was compared with the general population, the standardized incidence ratios for suicide attempts rose from 0.89 (95% confidence interval, 0.54–1.37) at 3 years before treatment to 1.36 (95% CI, 0.65–2.50) in the year before treatment for first attempts, and from 0.99 (95% CI, 0.65–1.44) at 3 years before treatment to 1.57 (95% CI, 0.86–2.63) in the year before treatment for all attempts.

The risks were shown to be highest within 6 months after the start of treatment: 1.93 (95% CI, 1.08–3.18) for first attempts and 1.78 (95% CI, 1.04–2.85) for all attempts. The investigators also found that women who made suicide attempts received two or three treatments more often than did women who did not attempt suicide, suggesting treatment failure as a possible contributor.

After treatment, the standardized incidence ratio declined to 0.97 (95% CI, 0.64–1.40) for first attempts and 1.04 (95% CI, 0.74–1.43) for all attempts within 3 years. After 3 years and for the duration of follow-up, the rate remained on par with the background rate for the population.

The investigators concluded that “an increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin.” However, they wrote, “the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established.” Patients with a history of suicide attempts need not be denied treatment with isotretinoin, they wrote, but “close monitoring of patients for suicidal behavior for up to a year after treatment has ended” would be advisable (BMJ 2010 Nov. 12 [doi:10/1136/bmj.c5812]).

The investigators acknowledged some limitations of their study, including a lack of data on potential confounding factors other than age, sex, and calendar year. Low statistical precision was also a limitation: Although standardized incidence ratios were clearly rising before treatment, they wrote, “we found no statistical significance until six months after treatment. In the internal cohort crossover analysis – that is, analyzing outcomes before and after treatment in the same population – the differences in incidence did not reach statistical significance, making the estimated number needed to harm uncertain.”

Also, they wrote, “we had no information on the effect of treatment. A bias would exist if the patients who made suicide attempts had a poorer effect of treatment than did those who did not make such attempts. In that case, the suicidal behavior should be attributed to the treatment resistant acne and not to the treatment. However, such bias would only strengthen the assumed association between severe acne and suicidal behavior.”

In an editorial comment, Dr. Parker Magin of the University of Newcastle in Callaghan, New South Wales, Australia, and Dr. John Sullivan of the University of New South Wales in Sydney, said that clinicians could draw important practical conclusions from the study – namely, that during and after treatment with isotretinoin (and especially when treatment is unsuccessful), “patients should be carefully monitored for depression and suicidal thoughts. Patients probably have an increased risk before treatment, however, so all patients with acne of a severity for which isotretinoin is indicated should have psychosocial factors and suicidal intent monitored.”

As for who should perform the monitoring, Dr. Magin said that although dermatologists generally take on that role, general practitioners “have more appropriate training and experience in psychological medicine … and could add invaluable expertise in the psychological aspects of management in a shared care model with dermatologists.” Families of patients, Dr. Magin added, may also help with monitoring. (BMJ 2010 Nov. 12 [doi:10.1136/bmj.c5866])

The study was funded by the Swedish Research Council. Mr. Sundström and his coauthors declared that they had no conflicts of interest. Dr. Magin and Dr. Sullivan have been members of All About Acne, an organization supported by unrestricted educational grants from drug companies. Neither Dr. Magin nor Dr. Sullivan received payment from the organization, and the drug companies that provide support do not manufacture isotretinoin.