When risks outweigh benefits

Concern rises over finding the balance between positive and negative effects of antidepressants, writes EOIN BURKE-KENNEDY

DRUG-MAKER GlaxoSmithKline was recently ordered to pay $2.5 million (€1.7 million) over claims its Seroxat antidepressant, sold as Paxil in the US, caused birth defects.

The case was brought by the family of three-year-old Lyam Kilker, who was born with two holes in his heart – birth defects his mother blames on the antidepressant.

A court in Philadelphia found the company had failed to adequately warn doctors and pregnant users of the risks associated with the drug.

GlaxoSmithKline says it intends to appeal the verdict on the grounds the scientific evidence did not establish that exposure to Paxil during pregnancy caused the child’s condition.

The case is the first of 600 such trials due before the US courts, and the verdict is likely to exacerbate public concern about the use of antidepressants.

Earlier this year, the Irish Medicines Board (IMB) advised pregnant women against taking Seroxat, and urged women wanting to become pregnant and who are taking the drug to carefully consider the risks and benefits before continuing on the medication.

Some studies have found an increased risk of birth defects, particularly heart defects, associated with the use of Seroxat during the first three months of pregnancy.

The problem with assessing the risks associated with antidepressants is that there are hundreds of studies relating to their efficacy and side effects, many of which contradict each other, and an equal number of experts making claims and counter claims.

The British Medical Journal has published a study suggesting young adults are twice as likely to experience suicidal thoughts while taking antidepressants, than older people who are prescribed the same medication.

Here, the mother and stepfather of Shane Clancy, who killed student Sebastian Creane and stabbed two others before taking his own life, have said they believe antidepressants played a role in their son’s behaviour.

Concern over the side effects of antidepressants has prompted the Irish Medicines Board to include a leaflet inside antidepressant prescription boxes, warning the medicines may sometimes be associated with “thoughts of harming or killing yourself” in the early stages of use.

Several leading Irish psychiatrists have voiced concern that misleading and sensationalist claims in the media about antidepressants might encourage vulnerable people who have been prescribed the drugs to discontinue their medication.

They say the efficacy and safety of antidepressants have been rigorously scrutinised by regulatory authorities such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMEA), and the Irish Medicines Board (IMB).

They insist antidepressants have transformed the lives of millions of people with depressive illnesses, who would otherwise have needed hospital treatment.

They also warn that some studies have linked a reduction in prescription rates for antidepressants to a rise in suicides in several industrialised countries.

Irish psychiatrist Prof David Healy, who is based at Cardiff University, believes the problem with assessing the efficacy of antidepressants is that doctors are using a variety of different drugs, whose effects are not fully understood, to treat a range of mood disturbances which are even less well understood.

Healy says some antidepressants have an energy-enhancing effect, while others like Prozac and Seroxat have an anxiety-relieving effect. “These drugs may or may not be helpful to someone who is depressed.”

Healy says prescribing an antidepressant requires careful consideration of what type of mood disturbance the patient is experiencing, and a close monitoring of the effects of the treatment.

The latest guidelines from the UK’s National Institute for Health and Clinical Excellence (Nice) on the treatment and care of people with depression and anxiety recommend antidepressants should not be used for the initial treatment of mild depression, because of the “poor risk-benefit ratio”.

The guidelines advise the medicines should ideally be used alongside cognitive behaviour therapy (CBT) and other “talk therapies” such as counselling.

In the past, psychiatrists drew a distinction between “melancholia”, which was considered a severe and protracted depression, and “reactive depression” whose less severe symptoms were brought on by an adverse life event. Nowadays the emphasis has shifted to seeing depression as a continuum from major to minor.

Critics have long accused the pharmaceutical industry of attempting to broaden the criteria governing depression – of pathologising unhappiness – in a cynical attempt to sell more medicines.

Between 300,000 and 400,000 people in Ireland suffer from some form of depression or anxiety. There are no reliable figures for the numbers taking antidepressants, but the general medical scheme (GMS) subsidises more than 1.1 million prescriptions annually for new-generation antidepressants.

These drugs, known as selective serotonin reuptake inhibitors (SSRIs) – which include Prozac and Seroxat – work by blocking the reuptake or recycling of the neurotransmitter serotonin.

The chemical theory of depression suggests a shortfall of neurotransmitters, such as serotonin and noradrenalin, produces the symptoms of depression and correcting this can help to reduce the symptoms.

But professor of psychology at the University of Hull, Irving Kirsch, believes SSRIs are no better than placebo in treating depression, as their biological effects are below the criteria for clinical significance.

He bases his controversial claim on an analysis of antidepressant medication data submitted to the FDA in the US.

He says a meta-analysis of the data for four commonly prescribed SSRIs avoids “the bias” caused by pharmaceutical companies selectively reporting only positive results.

Kirsch also believes there is now “no evidential support” for the prevailing chemical theory of depression, as the relationship between serotonin and mood has not been proved.

Professor of psychiatry at University College Cork, Ted Dinan, takes issues with Kirsch’s views.

“Whatever one’s biological view of depression, to say that the current licensed medications are nothing but glorified placeboes is utterly nonsense.”

Dinan insists the licensing of antidepressant medications requires large, multi-centred trials that must clearly show the medications are superior to placebo.