The debate over antidepressants and the risk of suicide continues to ferment, as new data again suggest a marked correlation between more cautious prescribing of selective serotonin re-uptake inhibitors (SSRIs) and sharp increases in suicide rates among children and adolescents.

A study published in the American Journal of Psychiatry (164: 1356-1363, September 2007) looked at prescription rates in the US and the Netherlands for SSRIs in children and adolescents aged up to 19 years between 2003 and 2005. It also examined suicide rates in these populations over the same period, at a time when US and European regulators were issuing public health warnings about a possible association between antidepressants and suicidal thinking and/or behaviour.

The researchers used Poisson regression analyses to determine the overall association between suicide rates and prescribing rates for antidepressants, adjusted for sex and age, in the periods preceding and immediately following the public health warnings.

They found that SSRI prescriptions for children and adolescents fell by around 22% in both the US and the Netherlands after the warnings went out. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005, showing “a significant inverse association with SSRI prescriptions”, the researchers said. In the US, and as previously reported, suicide rates for the 10- to 19-year age group rose by 14% between 2003 and 2004, the biggest year-to-year change in this population since the Centers for Disease Control and Prevention (CDC) began systematically collecting suicide data in 1979.

The research published in the American Journal of Psychiatry was led by Dr Robert Gibbons, director of the Center for Health Statistics and professor of biostatistics and psychiatry at the University of Illinois at Chicago. He recently reported in the same forum that an analysis of medical records from the US Veterans Administration healthcare system indicated SSRIs reduced the risk of suicide attempts in all four age groups studied, including young adults of 18-25 years.

According to Gibbons, the latest data suggest that every 20% decline in antidepressant use by patients of all ages in the US could mean an additional 3,040 suicides per year. The current US suicide rate is more than 32,000 per year.

CDC data

The new study coincided with the release of further CDC data on youth suicides, this time showing that the suicide rate for 10 to 24 year-olds in the US rose by 8% between 2003 and 2004, from 6.78 per 100,000 population to 7.32 per 100,000. This was the largest annual increase seen in 15 years for this age group and followed a decline of more than 28% in the suicide rate for 10 to 24 year-olds (from 9.48 to 6.78 per 100,000) between 1990 and 2003.

The US Food and Drug Administration introduced a ‘black box’ warning on antidepressants about increased risks of suicidal thoughts and behaviour in children and adolescents in October 2004. The decision was based on a meta-analysis showing that the average risk of suicidal behaviour or ‘suicidal ideation’ in more than 4,400 children and adolescents taking antidepressants was 4% compared with 2% on placebo.

The FDA action was heavily criticised by psychiatrists and others, who warned that it could put young people with depression at greater risk by discouraging off-label prescribing or scaring candidates for therapy and their parents away from treatment. The US agency recently asked antidepressant manufacturers to update the existing black box message to include warnings about increased risks of suicidal thinking and behaviour in people aged 18 to 24 during the first one to two months of treatment.

Bipolar diagnoses surge

The latest flurry of concern over the impact of public health warnings about antidepressants and youth suicide has also collided with new worries in the US about overprescribing of antipsychotics in the paediatric and adolescent populations.

Writing in the Archives of General Psychiatry (2007; 64:1032-1039), Dr Mark Olfson of the New York State Psychiatric Institute at Columbia University, National Institute of Mental Health (NIMH) researcher Dr Gonzalo Laje and colleagues reported that the number of visits to a doctor’s office resulting in a diagnosis of bipolar disorder in US children and adolescents up to the age of 19 years ballooned from an estimated 25 per 100,000 population in 1995-1995 to 1,003 per 100,000 in 2002-2003.

In the same periods, adult visits resulting in a diagnosis of bipolar disorder rose from 905 to 1,679 per 100,000 population. The evidence of a rapid increase in youth diagnoses comes at a time when a number of manufacturers of atypical antipsychotics are seeking – or have already obtained, in the case of Johnson & Johnson’s Risperdal (risperidone) – FDA approval for expanded indications to treat children and adolescents.

These approvals will mean antipsychotic manufacturers can start actively promoting the drugs for indications previously addressed ‘off-label’. In the Archives of General Psychiatry study, the researchers found that, between 1999 and 2003, 90.6% of youths and 86.4% of adults received a psychotropic drug during an office visit with a diagnosis of bipolar disorder.

Comparable rates of mood stabilizers, antipsychotics and antidepressants were prescribed for both age groups, although young patients were more likely to receive one of the newer atypical antipsychotics such as Abilify (aripiprazole, Bristol-Myers Squibb) or Zyprexa (olanzapine, Eli Lilly).

The surge in youth diagnoses of bipolar disorder is likely to reflect “a recent tendency to over-diagnose bipolar disorder in young people, a correction of historical under-recognition, or a combination of these trends”, suggested Olfson. “Clearly, we need to learn more about what criteria physicians in the community are actually using to diagnose bipolar disorder in children and adolescents, and how physicians are arriving at decisions concerning clinical management.”