J Mann A Clinical Perspective on Safety and Efficacy of SSRIs in Depressed Children and Adolescents J. John Mann, MD President, American Foundation for Suicide Prevention Chief, Department of Neuroscience New York State Psychiatric Institute

J Mann Depression can be Lethal but are SSRIs Safe and do They Prevent Suicide? Depression is not safe and is the leading cause of suicide. Suicide is the third leading cause of death in youth in the USA.Depression is not safe and is the leading cause of suicide. Suicide is the third leading cause of death in youth in the USA. Case reports of suicide attempts or ideation in treatment studies raise the question of whether they are due to illness or treatment? No suicides are reported in SSRI studies in depressed children or adolescents.Case reports of suicide attempts or ideation in treatment studies raise the question of whether they are due to illness or treatment? No suicides are reported in SSRI studies in depressed children or adolescents. Most suicides occur in untreated depressed persons.Most suicides occur in untreated depressed persons. Not treating depression may be lethal.Not treating depression may be lethal.

J Mann Psychological Autopsy Studies Identify Reasons for Suicide Suicide and suicide attempts in depressed adults are associated with no treatment, noncompliance with treatment or prescription of non-antidepressants.Suicide and suicide attempts in depressed adults are associated with no treatment, noncompliance with treatment or prescription of non-antidepressants. In an as yet unpublished report from the Utah Youth Suicide Study, Gray and colleagues (2003) reported that, of forty-nine adolescent suicides, 24 percent had been prescribed antidepressants, but none were positive for SSRIs at the time of their death.In an as yet unpublished report from the Utah Youth Suicide Study, Gray and colleagues (2003) reported that, of forty-nine adolescent suicides, 24 percent had been prescribed antidepressants, but none were positive for SSRIs at the time of their death. In NYC from , no paroxetine was found in 66 suicides under 18 yr and only 3/66 had any antidepressant detected.In NYC from , no paroxetine was found in 66 suicides under 18 yr and only 3/66 had any antidepressant detected.

J Mann Do SSRIs Antidepressants work in children and adolescents? Fluoxetine: three studies show efficacy (Emslie et al 1997, 2002 and TADS 2004).Fluoxetine: three studies show efficacy (Emslie et al 1997, 2002 and TADS 2004). Sertraline: one study shows efficacy (Wagner et al 2003). Combines two failed FDA studies.Sertraline: one study shows efficacy (Wagner et al 2003). Combines two failed FDA studies. Paroxetine: one positive study and two failed studies.Paroxetine: one positive study and two failed studies. Citalopram: one failed study and one possibly positive study.Citalopram: one failed study and one possibly positive study.

J Mann NonSSRI Antidepressant Lack Efficacy Venlafaxine: same as placebo in two studies.Venlafaxine: same as placebo in two studies. Nefazodone: one positive study (Emslie et al 2002) and one same as placebo.Nefazodone: one positive study (Emslie et al 2002) and one same as placebo. Mirtazapine: same as placebo in two studies.Mirtazapine: same as placebo in two studies. Tricyclics: no efficacy (Hazell et al 2002).Tricyclics: no efficacy (Hazell et al 2002).

J Mann Epidemiological Studies Link More Antidepressant Prescriptions to Falling Suicide Rates A decrease in suicide rate correlates with increased antidepressant use in Europe, Scandinavia, the United States and Australia.A decrease in suicide rate correlates with increased antidepressant use in Europe, Scandinavia, the United States and Australia. Doubling of prescriptions for serotonin reuptake inhibitors (SSRIs) correlated with a 25% decrease in the suicide rate in Sweden. Doubling of prescriptions for serotonin reuptake inhibitors (SSRIs) correlated with a 25% decrease in the suicide rate in Sweden. A study in Italy found the relationship between a 36% rise in prescription rates and an 18% decline in suicide rates only in females.A study in Italy found the relationship between a 36% rise in prescription rates and an 18% decline in suicide rates only in females. No change in suicide rate in Iceland despite 4 fold increase in SSRI usage. No effect in Japan.No change in suicide rate in Iceland despite 4 fold increase in SSRI usage. No effect in Japan.

J Mann Why Are Antidepressants Not Correlated With Suicide Rates In All Countries? Iceland had an 8 fold increase in alcohol per capita consumption in the last 50 years and only half the population who are prescribed antidepressants are actually taking the medication.Iceland had an 8 fold increase in alcohol per capita consumption in the last 50 years and only half the population who are prescribed antidepressants are actually taking the medication. Are the highest risk persons getting treated?Are the highest risk persons getting treated?

J Mann US Suicide Rates and Antidepressant Prescriptions The national suicide rate climbed 31% in the years 1957 to 1986, all prior to SSRIs.The national suicide rate climbed 31% in the years 1957 to 1986, all prior to SSRIs. Then, in 1987, just when SSRIs arrived, the suicide rate began to decline and that trend has continued to the present. Why?Then, in 1987, just when SSRIs arrived, the suicide rate began to decline and that trend has continued to the present. Why?

J Mann US Suicide Rates Fall While SSRI Prescriptions Increase From , the US suicide rate declined 13.5% and antidepressant prescription rates increased over four-fold.From , the US suicide rate declined 13.5% and antidepressant prescription rates increased over four-fold. Higher SSRI prescription rates associated with the falling national suicide rate even after controlling for unemployment and alcoholic beverage consumption rates (Grunebaum et al., 2004).Higher SSRI prescription rates associated with the falling national suicide rate even after controlling for unemployment and alcoholic beverage consumption rates (Grunebaum et al., 2004).

J Mann US Suicide Rates Fall Most In Those Who Receive More Antidepressant Prescriptions In females account for twice the antidepressant prescription volume (65-67%) compared to males (30-32%). Using age-adjusted rates, the decline in suicide rates was 22.5% for females and 12.8% for males [Grunebaum et al (2004)].

J Mann Suicide Rates Fell Most in Counties Throughout the USA that had the Highest Prescription Rates of SSRIs Confirmed in both adults (Gibbons et al) and youth (Olfson et al., 2003).Confirmed in both adults (Gibbons et al) and youth (Olfson et al., 2003).

J Mann Antidepressants are mostly prescribed for depression in the USA Mood disorders accounted for 45% of antidepressant prescriptions in 1997 and 59% in 2000.Mood disorders accounted for 45% of antidepressant prescriptions in 1997 and 59% in 2000.

J Mann Quantifying the Relationship of Suicide Rates and Antidepressant Prescription Rate For every 10% increase in the total antidepressant prescription rate (15 million more antidepressant prescriptions), the national suicide rate decreased by 3% (968 fewer suicides).For every 10% increase in the total antidepressant prescription rate (15 million more antidepressant prescriptions), the national suicide rate decreased by 3% (968 fewer suicides).

J Mann Summary Areas of the US with the biggest increases in SSRI prescriptions are associated with the biggest declines in youth suicide rates (Olfson et al 2003).Areas of the US with the biggest increases in SSRI prescriptions are associated with the biggest declines in youth suicide rates (Olfson et al 2003). Most suicides in adults or youth with major depression occur in untreated persons.Most suicides in adults or youth with major depression occur in untreated persons. These findings indicate that untreated depression is the main cause of suicide and treatment can save a lot of lives.These findings indicate that untreated depression is the main cause of suicide and treatment can save a lot of lives.