21 July 2004

Antidepressant/suicide link?

Recently, the media has highlighted the reported link between suicidality and antidepressants. But research conclusions are contradictory. This has left parents in a quandary: should or shouldn't their kids take antidepressants?

Recently, the media has highlighted the reported link between suicidality and antidepressants. Research developments led the US Food and Drug Administration to ask manufacturers of 10 different antidepressants to include a new warning section and British authorities to issue a warning against the use of some antidepressant in children.

But research conclusions are contradictory. This has left parents in a quandary: should or shouldn't their kids be taking these drugs?

One study, which appears in the April 24 issue of The Lancet, found that when data from both published and unpublished trials were combined, the risks for children taking selective serotonin reuptake inhibitors (SSRIs) and another drug, Efexor, outweighed any possible benefits from these medications. The only exception was fluoxetine, marketed under the brand name Prozac, which had a favourable risk-benefit profile.

"I'm not sure these drugs are any better than placebo," said study co-author Dr Tim Kendall, co-director of the American National Collaborating Centre for Mental Health in London. "I'm not sure it's worth using SSRIs, and it may even be dangerous, with the exception of fluoxetine."

Kendall said the researchers reviewed a total of 12 studies - six published, six unpublished - that compared the use of various SSRIs to treatment with a placebo.

The researchers found fluoxetine (Prozac) had a favourable risk-benefit profile, which means the benefits from taking the drug outweigh any potential risks, such as drug side effects or an increased risk of suicide.

Other SSRIs didn't fare as well. Paroxetine (Aropax) and sertraline (Zoloft) had a slightly favourable risk-benefit profile when only the published data was examined. Once the unpublished data was added, however, the risks of taking these medications outweighed the potential benefits. Both citalopram (Cipramil) and venlafaxine (Efexor, which is not an SSRI) also had unfavourable risk-benefit profiles.

Confusing research
In an accompanying editorial, The Lancet editors write, "The story of research into selective serotonin reuptake inhibitor use in childhood depression is one of confusion, manipulation and institutional failure. Although published evidence was inconsistent at best, use of SSRIs to treat childhood depression has been encouraged by pharmaceutical companies and clinicians worldwide."

Another study published in the July 21 issue of the Journal of the American Medical Association, found the risk of suicidal behaviour was similar for four antidepressants: amitriptyline, fluoxetine, paroxetine and dothiepin. Amitriptyline and dothiepin are older medicines called tricyclics, while fluoxetine and paroxetine are SSRIs.

However, the risk of suicidal behaviour was almost three times as likely to occur during the first month of use as after the first three months.

"One possible explanation is that when somebody finally goes to see their doctor, they're at the height of depression and in an extremely vulnerable place, and it takes antidepressants a while to take effect," said study co-author Susan Jick, an associate professor of epidemiology at Boston University School of Public Health.

Should children use antidepressants?
A South African expert thinks it is important for prescribers to monitor patients under the age of 18 years taking an SSRI or other antidepressant for signs of suicidal behaviour. But "the potential benefits of SSRIs and other newer antidepressants outweigh the risks. And we know depression, if left untreated, can also be fatal," says Dr Soraya Seedat, psychiatrist and co-director of the South African Medical Research Council's Unit on Anxiety Disorders.

A Cape Town child psychiatrist says that medication should be considered in chronic and/or severe cases of depression that do not respond to therapy alone and where the functioning of the child is significantly compromised. A strong family history of chronic, severe depression is also an indication for considering medication.

She stresses that medication should only be prescribed by a doctor with specialist training and/or experience in the field of child psychiatry. The parents need to give informed consent and be part of the decision-making team. Only medication registered for use in children or medication which has been subjected to high quality clinical trials with data published in peer review journals should be considered by the doctor. Medication which has not been supported by such evidence should be avoided.

Due to ethical limitations on testing new medications on children, this data is limited and only becomes available over time.

"It is the doctor's responsibility to be open with the parents about available knowledge and to carefully monitor the dosage, efficacy and side-effects of the medication. There are families who can testify to the value of anti-depressants in relieving significant distress in their children with no untoward effects and there certainly is a role for these treatments in the hands of qualified and experienced clinicians," she says.

Read more:
Depression Centre
Antidepros and child suicides


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