London Journal of Primary Care 2009;2:15–20

# 2009 Royal College of General Practitioners

Review Paper

Managing depression in childhood and adolescence Paul O Wilkinson MD MRCPsych University Lecturer and Honorary Consultant in Child and Adolescent Psychiatry, University of Cambridge Section of Developmental Psychiatry, Cambridge, UK

Key messages . . . .

Depression is an important and relatively common illness in children and adolescents. Depressed patients may present to the GP for many reasons other than depression. Depression is treatable, using psychological, medication and social interventions. Cases of moderate-severe depression should be referred to secondary care.

Why this matters to me Depression is an important and common condition that leads to a lot of suffering and adverse social consequences, such as poor school performance

and the loss of friendships. The longer an illness lasts, the greater the social consequences, and sometimes these effects cannot be reversed (for example, poor GCSE results). Many cases are never diagnosed, let alone treated. This is partly because adolescents themselves do not realise this is a problem that can be treated, partly because their parents do not recognise the changes in their adolescent. Many of these adolescents visit their GP, often for incidental problems irrelevant to their depression, sometimes for problems that are due to the depression (such as anger, or school failure). My hope is that if GPs are more aware of depression, they are more likely to ask about it and therefore diagnose it and treat it.

ABSTRACT This paper describes depression (a syndrome of low mood/irritability/lack of pleasure with associated physical and cognitive symptoms) in children and adolescents. It aims to help GPs to recognise more cases of it. It discusses why some young people do become depressed and will describe the treatments which are available, and how treatment may be implemented in the primary care setting. Current UK NICE guidelines recommend that: (i) psychological treatments should be offered as first-line treatment for moderate to severe depression and persistent mild depression; (ii) if this is not effective after four to six sessions, co-existing factors such as social stresses and family discord should be considered and addressed; (iii) an antidepressant (fluoxetine) Clinical depression is more than feeling sad. It is a syndrome of persistent emotional, biological and psychological symptoms, accompanied by impaired social functioning. This disorder is relatively common in children and, especially, adolescents, yet is often unrecognised and untreated. It is often caused by

should only be considered after four to six sessions; (iv) antidepressants should only be offered in conjunction with psychological treatment. These guidelines are not in full agreement with large randomised controlled trials that demonstrate that fluoxetine is more effective than CBT; and that show equivocal benefit of combined fluoxetine and CBT over fluoxetine alone. Part of the reason for the predominance of psychological treatments in these guidelines is the small but significant risk of suicidality with fluoxetine.

Keywords: adolescent, antidepressive agents, child depression, psychological techniques environmental adversities, such as acute life events, family dysfunction or chronic child abuse. A range of treatments have been shown to effectively treat this condition. More effective recognition and implementation of evidence-based treatments would undoubtedly improve the wellbeing and functioning of the

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paediatric population. The GP is in a unique position both to recognise depression in the community and to be able to identify relevant features of the depressed adolescent’s environment. This paper aims to describe the depressive syndrome and help primary health care workers to recognise more cases of it. It will also discuss why some young people do become depressed and will describe the treatments which are available, and how treatment may be implemented in the primary care setting.

Diagnosis of depression Box 1 shows DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition)1 criteria for a diagnosis of major depression. Dysthymic disorder is a more chronic, less severe condition, consisting of depressed mood for most of the time, with at least two other depressive symptoms, lasting at least one year, and in which criteria for a major depressive episode are not met for the first year. The threshold of five symptoms is fairly arbitrary, as it has been shown that there is a gradual reduction in social functioning with more symptoms and that older adolescents with subthreshold depressive symptoms are as likely as those with the full depressive syndrome to develop a subsequent depressive disorder.2,3 As stated in the RCGP Mental Health and Primary Care Position Statement, 2004, ‘How someone is able to function within a family and a community is more important than their diagnostic label’.4 Assessing a patient’s reduction in social functioning is much more important than counting their symptoms when deciding whether to impart a diagnosis of depression.

Epidemiology of depression Over a six month period, 2% of post-pubertal adolescents are likely to meet criteria for a severe depressive disorder and 4% for a mild to moderate disorder; 1– 2% of pre-pubertal children are likely to meet criteria for depression.5 Depression is much more common in girls after 13, but slightly more common in boys before 13.5 The majority of young people with depression also have at least one co-morbid psychiatric disorder, the most common being behaviour disorders (40%) and anxiety disorders (34%).6

Causes of depression Each individual with depression often has multiple contributory factors. It is important to try to identify

Box 1 DSM-IV Diagnostic criteria for paediatric major depressive episode 1 At least five depressive symptoms must have been present most of the time for two weeks and represent a change from previous functioning. At least one of the symptoms must be: . depressed or irritable mood . markedly diminished interest or pleasure in almost all activities. Other possible symptoms are: decreased or increased weight or appetite . increased or decreased sleep . psychomotor agitation (fidgetiness) or retardation (slowed down speech/movements) . reduced energy . worthlessness or excessive guilt . reduced concentration or indecisiveness . recurrent thoughts of death or suicidal ideation. .

2 There must be significant distress or impairment in functioning (such as at school, with friends or with the family). 3 Symptoms must not be due to a medical condition, medication, illicit substances or bereavement.

these in the assessment, so that where possible, they can be addressed. As with most conditions, children whose parents have depressive disorders are at increased risk of developing depression themselves.7,8 This is likely to be due to both genetic effects and the environmental effects of living with a parent with depression. Children with certain temperaments or thinking styles, such as emotionality and self-blaming, are at increased risk for depression. Depression is often precipitated by life-events, especially disappointments and permanent losses.9 Chronic stress, including abuse, is a major predisposing factor for depression. The GP is likely to be in a very good position to know about and understand the social context, and potential causal/protective factors, of a depressed child/adolescent and their family.

Recognition of depression Some young people with depression may present to primary care complaining of depressed mood. However, some may present with symptoms of a co-morbid disorder, such as anxiety or temper outbursts, and some may present with more general complaints of reduced function, such as school non-attendance, finding

Managing depression in childhood and adolescence

schoolwork more difficult or social withdrawal. Some, especially younger children, may present with headaches or abdominal pain. Owing to the great variation in presentation, it is imperative that primary health care workers maintain a high index of suspicion for depression: it is important to always ask about depressive symptoms in any young person presenting with any depressive symptoms, any psychiatric symptoms, any pain without an organic explanation or reduced psychosocial functioning. As stated in the RCGP position statement, ‘Delay in diagnosis, failure to involve patients in treatment and poor follow up can lead to further deterioration of illnesses such as ... depression’.4

The initial interview Once it has been established that a young person may suffer from a depressive disorder, several areas need to be enquired about. Owing to increased suicide risk, they must be asked if they have had thoughts that life is not worth living, and if so, whether they have made any plans to take their own lives. It is important to ask about other co-morbid conditions, in particular anxiety disorders, behaviour disorders and obsessive-compulsive disorders, as these are likely to require treatment in their own right. Occasionally, the depressive disorder is part of a bipolar disorder or psychotic disorder, so the young person should be asked whether their mood has ever felt high or out-of-control and if they have suffered from psychotic symptoms, such as voices or thoughts that people are wanting to hurt them. Alcohol or illicit drug use may be present and may complicate treatment, so should always be enquired about. The young person and their family may be surprised that they have been diagnosed with depression if they attended complaining of a seemingly-different problem, therefore it is important to be sensitive when giving the diagnosis.

Treatment Initial intervention The first line of management for non-severe depression should be a mixture of psychoeducation (explanation of depression, its causes, its treatment and its treatability); support, such as giving the young person a chance to talk about their problems; and practical interventions on potential causative factors, such as asking the school to try to stop any bullying or treating

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parental depression. It has been suggested that a mixture of this brief initial intervention and the natural remission rate of depression will lead to remission in around a third of cases of mild to moderate depression.10 Exercise and improved diet may be helpful.11 It is often feasible for this intervention to be delivered by primary care professionals. If the depression remains after four weeks of this intervention, it is important that the young person receives specialist targeted psychological and/or pharmacological treatment, which is often only available in specialist child and adolescent mental health services (CAMHS). The National Institute for Health and Clinical Excellence (NICE) has recommended that young people with moderate to severe depression should be reviewed by a specialist CAMHS.11

Addressing suicidality It is essential to ask depressed young people about suicidal thoughts. If these are strong or if they have been acted on, prompt referral to a child and adolescent psychiatrist is needed. Most young people with suicidal thoughts are managed as out-patients, due to both the shortage of child and adolescent psychiatric in-patient beds, and the ability of family members to support and keep safe their children. It is important that parents make sure that potential suicide methods, such as tablets, are kept locked or hidden away. Where suicidal intent is strong, the family may need to keep a constant watch on their child.

Psychological treatment Two individual short-term (8–16 sessions) psychological therapies have been shown in randomised controlled trials (RCTs) to be effective in paediatric depression: cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT). The main focuses of CBT are identifying unhelpful thoughts and behaviours and changing these to more positive ones. For example, the patient may find that they spend a lot of time in their room doing nothing, but if they do go out, they feel happier. They are therefore encouraged to go out more, and any barriers to this are tackled. Or they may find that they frequently blame themselves for negative events that are not their responsibility, making low mood worse. They are encouraged to look for any evidence that they are really to blame and to think of other possible explanations for which there is more evidence, and which do not lower their mood. Primary care professionals without formal CBT training can use some of these techniques when counselling their patients, such as encouraging them to do more enjoyable activities and thinking about whether it is fair to think some of their negative thoughts.

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Recent meta-analysis of 11 RCTs of CBT demonstrated that CBT is more effective than control treatments (moderate effect size of 0.53). However, more recent and more methodologically rigorous studies within this meta-analysis showed smaller effect sizes. In particular, the largest RCT (which included patients with higher severity of depression than previous studies) demonstrated no significant difference between CBT and inactive control (although secondary analysis demonstrated CBT to be more effective than control in adolescents from high-income families).12,13 The main focuses of IPT are to improve interpersonal functioning in one of four specific target areas (interpersonal role disputes, role transition, grief and interpersonal deficits) and therefore reduce linked depressive symptoms. Two RCTs have shown IPT to be significantly more effective than control treatments, whether delivered in a specialised clinic or by school-based clinicians.14,15 Combining these studies, recovery rate with IPT was 35/58 patients (60%) and in control groups was 21/53 patients (40%). While it is often important to address difficulties in family functioning as part of a treatment package, RCTs have not demonstrated that family therapy itself improves depressive symptoms.16–18 The only RCT which has tested individual psychodynamic psychotherapy for paediatric depression showed it to be equally effective to family therapy.19 However the lack of inactive control treatment makes it impossible to conclude that either treatment is more effective than no treatment.

Antidepressant medication Recent guidance by the UK Medicines and Healthcare products Regulatory Agency (MHRA) 20 and the National Institute for Health and Clinical Excellence (NICE) 11 stated that for children under 18, the only selective serotonin re-uptake inhibitor (SSRI) for which the evidence suggested that the benefits clearly outweigh the risks is fluoxetine. Three RCTs have now evaluated the efficacy of fluoxetine in paediatric depression. One hundred and fifty out of 266 patients (56%) allocated fluoxetine were much or very much improved at end-point, compared to 92 of 261 patients (35%) allocated to placebo. The MHRA concluded that there were no or minimal benefits and increased side-effects (possibly including increased suicidality) for paroxetine,21 sertraline,22 citalopram and venlafaxine. In its 2005 draft guidelines, NICE recommended that sertraline or citalopram may be used if fluoxetine is not effective.11 A Cochrane meta-analysis of RCTs of tricyclic antidepressants showed no difference in improvement rates between medication and placebo in children and adolescents

with depression.23 There have been no studies of St John’s Wort in paediatric depression. Some psychiatrists have argued that as RCTs have excluded many patients with more severe depression and suicidality, the results underestimate the benefits of medication in their more severely depressed patients. Both the MHRA and NICE have recommended that antidepressants should only be prescribed following assessment by a specialist (defined as a child and adolescent psychiatrist by NICE). This is mainly due to the risk of suicidality and self-harm with SSRIs (a meta-analysis by NICE showed a 4.1% incidence of suicidal ideation/behaviour in patients randomised to SSRIs and 2.7% in the placebo group, which was statistically significant). It is very important that young people are monitored carefully, in particular for agitation, hostility and suicidality, when prescribed an SSRI. Common physical side-effects include tiredness, headache and gastro-intestinal disturbances. Antidepressants should be continued for at least six months after the resolution of symptoms,24 due to a doubled rate of relapse 25 if they are discontinued too soon.

Comparing physical and psychological treatments Several RCTs have compared physical and psychological treatments: the TADS study showed that the combination of fluoxetine and placebo (improvement in 71% of patients) was significantly more effective than either fluoxetine alone (improvement in 61%) or CBT alone (improvement in 43%).12 Secondary analysis demonstrated that combined treatment was only more effective than medication alone if depression was severe.13 Fluoxetine alone was significantly more effective than CBT alone but there were significantly more episodes of suicidality and self-harm in patients randomised to the fluoxetine than the non-fluoxetine groups. Two other studies have demonstrated no significant difference between combined CBT and fluoxetine over fluoxetine with standard non-specific out-patient treatment.26,27 One of these studies was the largest UK study of adolescent depression (Adolescent Depression Antidepressants and Psychotherapy Trial), which also included the most severely depressed patients of any of the published studies.26

Current treatment recommendations NICE has recommended that psychological treatments (CBT, IPT or family therapy) should be offered as first-line treatment for moderate to severe depression

Managing depression in childhood and adolescence

and persistent mild depression. If this is not effective after four to six sessions, co-existing factors such as social stresses and family discord should be considered and addressed; fluoxetine should also be considered at this stage. Antidepressants should only be offered in conjunction with psychological treatment. Part of the reason for the prominence of psychological over medication therapy in the NICE guidelines is the risk of suicidality from adolescents. Individual child psychotherapy or structured family therapy should be considered if combined psychological treatment and fluoxetine is not effective or the family are reluctant for fluoxetine to be prescribed. It is important that any co-morbid conditions, such as alcohol dependence and anxiety disorders are treated together with the depression. It is noticeable that these guidelines are not in full agreement with the results of the UK ADAPT study,26 which was published soon after the NICE guidelines, which suggested that adding CBT to fluoxetine and standard out-patient management does not lead to additional benefit; nor the American TADS study,12 which suggested that fluoxetine is more effective than CBT. For this reason (and the fact that CBT and IPT resources are so limited), UK child and adolescent mental health clinics do vary in the treatment they offer.

Outcome Sadly, a significant number of young people with depression remain depressed for a long time, despite treatment. One study of cases of depression in a specialist CAMHS clinic showed that at 36 weeks, half were still depressed, a quarter had recovered and a quarter no longer had depression, but still had a comorbid disorder.28 Depression in adolescents approximately doubles the risk of an episode of depression in young adult life.29 Hopefully the wider use of evidence-based treatments will lead to better outcome in adolescents in future than at the time earlier studies took place.

Conclusion Depression is relatively common in children and adolescents but is often unrecognised. It is important that it is considered in young people presenting with a range of problems so that depressed youngsters are identified and then able to receive treatments that can dramatically improve their lives. Sadly, there is often a waiting list to access these specialist treatments. However, there are a range of interventions that can be

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given by primary care professionals that may help these patients while they are waiting. CONFLICTS OF INTEREST

None. REFERENCES 1 Association AP. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association, 1994. 2 Pickles A, Rowe R, Simonoff E, Foley D, Rutter M and Silberg J. Child psychiatric symptoms and psychosocial impairment: relationship and prognostic significance. British Journal of Psychiatry 2001;179:230–5. 3 Fergusson DM, Horwood LJ, Ridder EM and Beautrais AL. Subthreshold depression in adolescence and mental health outcomes in adulthood. Archives of General Psychiatry 2005;62(1):66–72. 4 RCGP. Royal College of General Practitioners Position Statement: Mental Health and Primary Care, 2004. www.rcgp.org.uk/PDF/clinspec_printed%20version%20 mental%20health.pdf (accessed 2 January 2009). 5 Angold A and Costello EJ (eds). The Epidemiology of Depression in Children and Adolescents, 2nd edn. Cambridge: Cambridge University Press, 2001. 6 Angold A, Costello EJ and Erkanli A. Comorbidity. Journal of Child Psychology and Psychiatry 1999;40(1): 57–87. 7 Weissman MM, Warner V, Wickramaratne P, Moreau D and Olfson M. Offspring of depressed parents. 10 Years later. Archives of General Psychiatry 1997;54(10): 932–40. 8 Wickramaratne PJ and Weissman MM. Onset of psychopathology in offspring by developmental phase and parental depression. Journal of the American Academy of Child and Adolescent Psychiatry 1998;37(9):933–42. 9 Goodyer IM, Herbert J, Tamplin A and Altham PM. Recent life events, cortisol, dehydroepiandrosterone and the onset of major depression in high-risk adolescents. British Journal of Psychiatry 2000;177:499–504. 10 Harrington R. Affective disorders. In: Rutter M and Taylor E (eds) Child and Adolescent Psychiatry, 4th edn. Malden: Blackwell, 2002, pp.463–85. 11 NICE. Depression in Children and Young People: identification and management in primary, community and secondary care. London: British Psychological Society, Royal College of Psychiatrists, 2005. www.nice.org.uk/ CG028 12 March J, Silva S, Petrycki S et al. Fluoxetine, cognitivebehavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. Journal of the American Medical Association 2004; 292(7):807–20. 13 Curry J, Rohde P, Simons A et al. Predictors and moderators of acute outcome in the treatment for adolescents with depression study (TADS). Journal of

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the American Academy of Child and Adolescent Psychiatry 2006;45:1427–39. Mufson L, Weissman MM, Moreau D and Garfinkel R. Efficacy of interpersonal psychotherapy for depressed adolescents. Archives of General Psychiatry 1999;56(6): 573–9. Mufson L, Dorta KP, Wickramaratne P, Nomura Y, Olfson M and Weissman MM. A randomized effectiveness trial of interpersonal psychotherapy for depressed adolescents. Archives of General Psychiatry 2004;61(6): 577–84. Lewinsohn PM, Clarke GN, Hops H et al. Cognitivebehavioral treatment for depressed adolescents. Behavior Therapy 1990;21:385–401. Brent DA, Holder D, Kolko D et al. A clinical psychotherapy trial for adolescent depression comparing cognitive, family, and supportive therapy. Archives of General Psychiatry 1997;54(9):877–85. Harrington R, Kerfoot M, Dyer E et al. Randomized trial of a home-based family intervention for children who have deliberately poisoned themselves. Journal of the American Academy of Child and Adolescent Psychiatry 1998;37(5):512–8. rowell J, Joffe I, Campbell J et al. Childhood depression: a place for psychotherapy. An outcome study comparing individual psychodynamic psychotherapy and family therapy. European Child and Adolescent Psychiatry 2007; 16(3):157–67. MHRA. Medicines and Healthcare Products Regulatory Agency, 2003. www.mhra.gov.uk/NewsCentre/Pressreleases/ CON002045 (accessed 16 June 2004) Keller MB, Ryan ND, Strober M et al. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry 2001;40(7):762–72. Wagner KD, Ambrosini P, Rynn M et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. Journal of the American Medical Association 2003;290(8):1033–41. Hazell P, O0 Connell D, Heathcote D and Henry D. Tricyclic drugs for depression in children and adolescents. Cochrane Database System Review 2002(2): CD002317.

24 NICE NIfCE. Depression in Children: identification and management of depression in children and young people in primary, community and secondary care. Draft for first consultation. London: NICE, 2004. 25 Emslie GJ, Heiligenstein JH, Hoog SL et al. Fluoxetine treatment for prevention of relapse of depression in children and adolescents: a double-blind, placebo-controlled study. Journal of the American Academy of Child and Adolescent Psychiatry 2004;43(11):1397–405. 26 Goodyer I, Dubicka B, Wilkinson P et al. Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial. BMJ 2007;335(7611):142. 27 Clarke G, Debar L, Lynch F et al. A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication. Journal of the American Academy of Child and Adolescent Psychiatry 2005;44(9):888–98. 28 Goodyer IM, Herbert J, Secher SM and Pearson J. ShortTerm Outcome of Major Depression: I. Comorbidity and Severity at Presentation as Predictors of Persistent Disorder. Journal of the American Academy of Child and Adolescent Psychiatry 1997;36(2):179–87. 29 Weissman MM, Wolk S, Goldstein RB et al. Depressed adolescents grown up. Journal of the American Medical Association 1999;281(18):1707–13.

ADDRESS FOR CORRESPONDENCE

Paul O Wilkinson Clinical Lecturer and Locum Consultant in Child and Adolescent Psychiatry University of Cambridge Section of Developmental Psychiatry Douglas House, 18b Trumpington Road Cambridge CB2 8AH UK Tel: +44 (0)1223 746001 Email: [email protected]

Managing depression in childhood and adolescence.

This paper describes depression (a syndrome of low mood/irritability/lack of pleasure with associated physical and cognitive symptoms) in children and...
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