Children, serotonin and suicide
- Joseph M. Rey
- Aust Prescr 2005;28:111-3
- 1 October 2005
- DOI: 10.18773/austprescr.2005.086
see also "Suicide and antidepressants in children "
Controlled trials show that psychosocial treatments such as cognitive behaviour therapyand interpersonal psychotherapy are effective in mild to moderate paediatric depression. However, effectiveness in severe depression (when symptoms are serious and last more than six weeks in at least two of three contexts - home, school, peers) is questionable.2 This raises the question of drug treatment.
Tricyclic antidepressants are not more effective than placebo in children and adolescents.3They are cardiotoxic, particularly in overdose, and are therefore not recommended. A meta-analysis of data from published and unpublished randomised controlled trials (practically all company-sponsored) that evaluated a selective serotonin reuptake inhibitor (SSRI) versus placebo in patients aged 5-18 years concluded that only fluoxetine had evidence of effectiveness.4 A recent randomised trial funded by the US National Institute of Mental Health also showed response rates were higher with fluoxetine (61%) than placebo (35%) or cognitive behaviour therapy (43%) in severely depressed adolescents when global clinical improvement was considered. Combined fluoxetine and cognitive behaviour therapy worked best (71%).2
SSRIs are less toxic and have fewer unwanted effects than tricyclic antidepressants, but it has been suggested that, paradoxically, SSRIs may induce suicidal behaviour in the young. Ascertaining whether this is true is not easy because depression also increases the risk of suicide. So far, data are contradictory. On the one hand, pharmacoepidemiological and ecological studies suggest that increased use of SSRIs may have resulted in a reduction in youth suicide and that SSRIs are not found more often than expected in young suicide victims. On the other hand, a review5 by the US Food and Drug Administration of 24 controlled trials involving more than 4400 children and adolescents showed a robust if small (2%) short-term increase in the incidence of suicidality (suicidal thoughts, attempts) in those receiving antidepressants, mostly SSRIs, compared with placebo. There were no suicides. The mechanisms underlying increased suicidality are unclear. SSRIs, particularly paroxetine5, can induce akathisia, agitation and irritability (so-called 'activation'). Symptoms of 'activation' may be an indicator of increased suicide risk. Like other antidepressants, SSRIs can also trigger manic switches.
This is a rapidly evolving field in which new data are becoming available all the time and clinicians need to change their practice accordingly, considering that the balance between benefit and harm is neither simple nor static. Conclusions derived from clinical trials may not apply to individual patients for methodological, genetic, physiological, psychosocial and cultural reasons. Also, the weight given to the evidence may vary in line with changes in personal and social values. Electroconvulsive therapy is a case in point.6 (Ironically, electroconvulsive therapy could become an increasingly attractive treatment option for youth depression due to concerns about antidepressants.) Hence, clinical practice should be guided by a careful appraisal of benefit and harm based on best evidence, clinical experience, and the needs, circumstances and wishes of each individual patient.
SSRIs have been widely used 'off-label' from the early 1990s, but none is formally approved for paediatric depression in Australia. The data about effectiveness are not great. The risks are small, but real. Conversely, depression is a serious illness that produces much personal suffering and can lead to social problems, poor physical health and suicide. Given a high recurrence rate, the effects of depression can be particularly harmful during childhood and adolescence, the stage when personality, professional and social skills are developed. Yet, youth depression is often ignored, not diagnosed, and not treated. For example, an Australian national household survey showed that of all depressed adolescents, 11% had seen a GP or paediatrician, 17% had used mental health services, and only 3% had been prescribed antidepressants.7 The current evidence suggests that psychosocial treatments, not medication, should be used in mild and moderate depression, but they are no panacea.2 Delivering them can pose challenges because clinicians may lack skills and confidence in using these therapies. Psychosocial treatments may also be unavailable in public sector services or be difficult to access because of cost, long waiting lists, or lack of services (for example, in rural areas). Further, depressed young people may be more reluctant to become engaged in these treatments because of anger, lack of motivation or insight, and demoralisation. Fluoxetine has a place in the treatment of severe depression in the young.24 Fluoxetine and cognitive behaviour therapy should be the preferred option because the combination may be more effective and may reduce suicidal risk.2
When treatment with SSRIs is begun, the patients (and their families when appropriate - for example in younger adolescents) must be informed of the risk of increased suicidal thoughts and attempts, and adverse effects, so that they can detect 'activation', a manic switch, or an increase in suicidality, as well as discussing practical ways of dealing with them and enhancing patients' safety. This may require a reduction of the dose, because the adverse effects are dose-related. It is imperative to review patients often and monitor them closely for adverse effects, particularly during the first few weeks of treatment.
The Royal Australian and New Zealand College of Psychiatrists, the Royal Australasian College of Physicians and the Royal Australian College of General Practitioners have recently issued a statement about the use of antidepressants in children. This provides further guidance about the prescription of these drugs.8
Tiller J. Cognitive behaviour therapy in general practice. Aust Prescr 2001;24:33-7.
Professor Rey was a member of the advisory committees for atomoxetine (Eli Lilly) and methylphenidate (Janssen-Cilag) and was funded by Eli Lilly to attend an international conference.
Professor of Child and Adolescent Psychiatry, Northern Clinical School, University of Sydney, Sydney