In early 2009, two 16-year-old Queensland girls tragically hanged themselves within weeks of each other. The girls’ lives were plagued with abuse, self-harm and illicit drug use, and their deaths raised questions about the quality of care provided for troubled teens in the state.

A recent article in The Australian newspaper asked whether the antidepressant drugs prescribed to these girls may have contributed to their deaths.

This certainly isn’t the first time antidepressants have been linked to suicide. Think of Columbine’s Eric Harris, Australian newsreader Charmaine Dragun, and Daniel Smith, the son of celebrity Anna-Nicole Smith – all were likely harmed rather than helped by their antidepressant medication.

The issue of whether antidepressant use can trigger suicide, self-harm and violence in young people has been vigorously debated in recent years, but the argument has often generated more heat than light.

Let’s take a look at the evidence.

The rise of Prozac

When Prozac appeared on the market in the late 1980s it ushered in the era of “cosmetic psychopharmacology”.

Prozac seemed to be a miracle drug capable of making people with depression “better than well” and allowing non-depressed people to iron out their personality wrinkles pharmacologically.

But reports quickly emerged of users becoming uncharacteristically violent or suicidal on Prozac and other selective serotonin re-uptake inhibitors (SSRIs – a class of commonly prescribed antidepressants).

Definitive conclusions are hard to draw from a few case studies, particularly when the cases involve people with serious pre-existing emotional problems. So researchers look to “gold standard” randomised clinical trials for a clearer picture potential antidepressant harms.

Michiel1972

The good news is that adults on SSRIs are no more or less likely to attempt suicide than those taking sugar pills.

But give an antidepressant to an adolescent and you’re taking a gamble. On average, antidepressants double the chance of a young person making a suicide attempt. Some may be a little safer (Prozac) but others are particularly problematic (Paxil and Effexor).

Thankfully, suicide during clinical trials is very rare. So instead, most clinical trials rely on indirect measures of “suicidality”, indexed by suicidal thoughts or suicide attempts.

Regulation

In the past decade, guidelines on prescribing antidepressants to adolescents were updated to recognise these newly established risks. Currently in the United States and the United Kingdom, Prozac is the only antidepressant approved for adolescent depression.

In the US, all antidepressants have a mandatory black box warning of increased risk of suicide in under-25s.

And in Australia, no antidepressant is currently approved for the treatment of major depression in young people, although unapproved, “off-label” prescription is common.

Change of prescription

If antidepressants are culpable, you might expect changes in antidepressant prescribing would quickly impact adolescent suicide rates.

Antidepressant prescriptions for adolescents declined in the US after the black box warnings were introduced in 2004. Puzzlingly, though, initial reports suggested youth suicide in the US increased in this same period. This negative correlation suggests antidepressants might actually save lives.

But correlation does not mean causation. Careful examination of the data revealed the increase in suicide rates actually preceded the drop in SSRI prescriptions. And more recent analyses show the youth suicide rate in the US has since fallen to its lowest level in 25 years.

John Brawley

Help or harm?

The clincher for this whole issue is whether antidepressants help more teenagers and young adults than they hurt. If antidepressants cause suicidal thoughts in an unlucky few but save hundreds from disabling depression, it’s worth using them, isn’t it?

The unfortunate fact is that antidepressants often don’t help young people with depression – or many adults, for that matter. A famous Guardian headline in 2008 stated scientists believed Prozac, which was used by 40 million people, didn’t work. It referred to the classic meta-analysis by Irving Kirsch showing negligible efficacy of antidepressants in those with mild to moderate depression.

In the average paediatric antidepressant clinical trial, roughly as many depressed participants improve on placebos as on the drug itself. Prozac is the only antidepressant to consistently show any benefit (albeit minor) over placebo for depressed people in this age group.

And even these so-called “positive” trials are sometimes so mired in Big Pharma obfuscation that they require teams of forensic statisticians to expose the truth.

The scandal of “Study 329” and the emerging concerns about TADS (Treatment of Adolescents with Depression Study) is a prime example of inconvenient data being moulded into shape by suspect statistics, selective reporting and data cleaning techniques.

Brain development

Recent theories of antidepressant action have moved beyond the simplistic notion of “correcting a serotonin imbalance” to embrace the idea of “neurogenesis”: antidepressants stimulate growth and repair in depressed brains that have been damaged by chronic stress.

The idea is controversial but provides a clue to why these drugs may disagree with adolescents.

It’s now widely accepted that the human brain undergoes major developmental changes up to the age of 25.

Flickr/Nick in exsillo

Antidepressants are likely suitable for a stressed, mature brain, but their neurogenic effects collide with brains that are still engaged in a frenzy of morphological transformation and therefore cause harm.

When antidepressants are given to adolescent lab rats, they create a “broken brain”, where normal development is disrupted and neurochemistry affected. This negatively impacts behaviour later in adulthood.

Weighing up the risks

Many young people will take antidepressants and have no adverse effects whatsoever. Some may even see improvements in their mood, at least in the short term.

But emerging evidence suggests that when adults or adolescents use antidepressants, minimal exposure (less than six months) may be best.

If you are taking antidepressant medication, be aware that abruptly stopping this treatment can lead to serious withdrawal effects. Anyone wishing to stop treatment should do so gradually and under supervision from a trusted medical practitioner.