To the Editor: Two recent items in the Journal might potentially lead to misinterpretation of the evidence on managing depression in young people.

The first was the book review entitled Darker side of “wonder drugs” by Jureidini1 in which there was no disclosure that the author of the review is president of Healthy Skepticism, a body which has been quite strident in its opposition to antidepressant therapy. The second was the unattributed comment in the editorial by Rey and Dudley describing “parents who believe their children killed themselves because they were taking SSRIs [selective serotonin reuptake inhibitors] . . .”,2 which may imply subtly that this has occurred frequently.

In a review of the United Kingdom General Practice Research Database of more than three million people,3 there were no suicides among the 6976 aged 10–19 years who had been prescribed one of two SSRIs or two tricyclic antidepressants; however, 15 people in that age group who had not received an antidepressant drug died by suicide. Furthermore, in a review of 14 857 suicides in Sweden, of the 52 involving people under 15 years, no SSRIs were detected, and in the 15–19-years age group, those taking SSRIs had a lower relative risk of commiting suicide than those taking other antidepressants.4

Clinicians with responsibility for children and adolescents can be reassured by these data, and also by the fact that the American Food and Drug Administration “black box” warning (their most potent warning) about antidepressants has recently been modified.5 Furthermore, the American Academy of Child and Adolescent Psychiatry and the American Psychiatric Association have provided a new resource about the use of medication in treating childhood and adolescent depression,6 which has been endorsed by over a dozen United States organisations comprising a “national coalition of concerned parents, providers, and professional associations”. This should allay questions that have rightly been raised, but that have been answered in favour of the judicious use of antidepressants, along with other therapeutic measures for children and adolescents with severe depression.

In view of the strong association between child and adolescent mood disorders and suicide,7 the above research findings and the recommendations of respected professional bodies raise the issue of potential legal action for not at least trialling antidepressant medication in young people with severe depression if non-pharmacological measures are ineffective.

To the Editor: Rey and Dudley cite clinical experience as the basis of their recommendation of selective serotonin reuptake inhibitors (SSRIs) — chiefly fluoxetine — for youth with severe depression plus severe impairment or failure of non-drug therapy.1 They do not discuss the evidence on efficacy because they claim that it is “ambiguous enough for scholars to be divided”. It is true that industry-funded scholars are continuing to suggest that SSRIs (chiefly fluoxetine) provide a worthwhile benefit.2 However, the evidence is unambiguous. The four published comparisons of fluoxetine versus placebo for children and adolescents have all been negative on their pre-specified primary endpoints.3,4 A tiny average benefit is likely, but the magnitude of this benefit is unlikely to exceed the magnitude of less frequent but more severe harms. Furthermore, the common clinical impression of worthwhile benefit is to be expected given the large average improvements seen in placebo groups.

Rey and Dudley speculate that psychosocial treatments may be less effective with uncooperative teenagers.1 However, that group may also be at higher risk of the dangers of intermittent use of, and overdosing with, antidepressant drugs.

Rey and Dudley cite Timimi’s critique of the concept of childhood depression5 as supporting “treating depression primarily as a moral or social problem”. However, Timimi did not even allude to depression as a moral problem, and advocated a multi-perspective approach that normalises emotional responses to adverse life experiences and includes interventions addressing biological factors, such as diet, exercise, and cognitive abilities. Rey and Dudley use a related straw-man argument in their final sentence when they suggest that the only alternatives to SSRIs are tricyclic antidepressants, victim blaming, and non-treatment.

Rey and Dudley deny being influenced by the gifts and funding that they have received from drug companies. There is compelling evidence that gifts and funding are effective, on average, for influencing beliefs, especially among people who have an illusion of invulnerability.6 We are not aware of any way that any individual can know that he or she has not been influenced.

In reply: The data available are inconclusive, but suggest that treatment with selective serotonin reuptake inhibitors (SSRIs) may increase the short-term (less than 14 weeks) risk of suicidal thoughts or self-harm in children and adolescents slightly, by about 2%. However, SSRI treatment may actually decrease the number of completed suicides,1 as Goldney also highlights. To show whether SSRIs influence the risk of completed suicide, a rare event, requires a randomised trial including up to two million individuals.2 This will not happen. Hence, clinicians must rely on accumulated data from experimental, epidemiological, and observational studies. Disagreements about interpretation will doubtless continue.

In response to Mansfield and colleagues, we personally know of media reports influencing some practitioners to revert to using tricyclic antidepressants, and child psychiatrists to avoid treating depressed adolescents. We do not shrink from our interpretation of the implications of Timimi’s reconceptualisation of “depression” as “unhappiness”. Regardless of how childhood depression is classified or named, we remain concerned that the impetus for clinicians to diagnose and treat it not be lost. Its social correlates include stigma and racism, which often involve seeing mental health problems as moral failures of character.

Our view is that fluoxetine shows a favourable harm–benefit profile in moderate to severe depression. According to the Treatment for Adolescents with Depression study,3 which was not funded by drug companies, four children need to be treated with fluoxetine for one to show much or very much improvement attributable to medication. This compares with having to treat 21 children for one to display a widely defined harm-related event. The numbers improve further when fluoxetine is combined with cognitve behavioural therapy (3 and 50, respectively). Pending new studies, clinicians would be unwise to ignore these data when treating serious depression in young people, a recurring illness that produces much suffering, physical and psychosocial disability, and suicide (odds ratio estimates ranging from 11.0 to 27.0).4 Our opinions are consistent with those of the recently released joint clinical guidance by the colleges of psychiatrists, general practitioners, and physicians.5

Mansfield and colleagues suggest that our editorial’s content might have been influenced by drug company gifts. We provided the educated readers of the Journal with information to judge this for themselves.

Comment: Three essentially independent reviews of the use of selective serotonin reuptake inhibitor (SSRI) antidepressants in children and adolescents have been undertaken in Australia in the past 9 months.1-3 The review by the Adverse Drug Reactions Advisory Committee1 had input from representatives of the Royal Australian and New Zealand College of Psychiatrists and the Division of Paediatric and Child Health, Royal Australasian College of Physicians (RACP).

All three reviews noted the paucity of information to support the efficacy of these and other antidepressants in children and adolescents, and the frequent observation of increased suicidal thoughts and self-harm in clinical trials.

The colleges’ review2 and the National Prescribing Service Rational Assessment of Drugs And Research (RADAR) review3 support the ADRAC advice that:

An SSRI should be chosen for a child or adolescent with MDD or other psychiatric condition only after taking into account the recent evaluations of clinical trial data and the Australian product information. Prescribers should be aware that the marketers of fluvoxamine and sertraline (indicated for obsessive compulsive disorder) advise against their use in children and adolescents with MDD, and the marketers of citalopram, escitalopram, paroxetine, venlafaxine and fluoxetine warn or caution against their use in patients aged less than 18 years for any indication.

It is important to note that children and adolescents who are being treated for MDD with an SSRI should not have their medication ceased abruptly.