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Using antidepressants in children and young people bring together all NICE guidance, quality standards and other NICE information on a specific topic. are interactive and designed to be used online. They are updated regularly as new NICE guidance is published. To view the latest version of this pathway see: http://pathways.nice.org.uk/pathways/depression Pathway last updated: 20 September 2016 This document contains a single pathway diagram and uses numbering to link the boxes to the associated recommendations. All rights reserved

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1 Child or young person with moderate to severe depression that is unresponsive to psychological therapy No additional information 2 Considering antidepressants in addition to psychological therapy Do not offer antidepressant medication to a child or young person with moderate to severe depression except in combination with a concurrent psychological therapy. Specific arrangements must be made for careful monitoring of adverse drug reactions, as well as for reviewing mental state and general progress; for example, weekly contact with the child or young person and their parent(s) or carer(s) for the first 4 weeks of treatment. The precise frequency will need to be decided on an individual basis, and recorded in the notes. In the event that psychological therapies are declined, medication may still be given, but as the young person will not be reviewed at psychological therapy sessions, the prescribing doctor should closely monitor the child or young person's progress on a regular basis and focus particularly on emergent adverse drug reactions. Following multidisciplinary review, cautiously consider fluoxetine 1 if moderate to severe depression in a child (5 11 years) is unresponsive to a specific psychological therapy after 4 to 6 sessions, although the evidence for fluoxetine's effectiveness in this age group is not established. Fluoxetine should be prescribed as this is the only antidepressant for which trials show that benefits outweigh the risks. Do not use: paroxetine and venlafaxine tricyclic antidepressants St John's wort. If patient is taking St John's wort (over the counter), inform them of the risks (there are no trials in children and young people upon which to make a clinical decision; unknown side-effect profile; known interactions with drugs, including contraceptives) and advise discontinuation while monitoring for recurrence of depression and assessing for alternative treatments in accordance with this pathway. Page 3 of 12

1 At the time of publication (April 2015), fluoxetine did not have a UK marketing authorisation for use in children under the age of 8 years. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices for further information. Page 4 of 12

Interactions Consider possible interactions with: other drugs (including recreational) alcohol complementary and alternative medicines. 3 NICE pathway on medicines optimisation See medicines optimisation 4 Information and monitoring Provide information Inform patients and their parent(s)/carer(s) about the: rationale for drug treatment delay in onset of effect time course of treatment possible side effects need to take the medication as prescribed. Supplement discussion with written information appropriate to the needs of the patient and parent(s)/carer(s), including the latest patient information advice from the relevant regulatory authority. Monitoring Unless medication needs to be started immediately, monitor symptoms that might be subsequently interpreted as side effects for 7 days before prescribing. Inform patients and their parent(s)/carer(s) that if there is any sign of new symptoms of these kinds, they should make urgent contact with the prescribing doctor. Arrange to carefully monitor adverse drug reactions (for example, weekly for the first 4 weeks of treatment) and record in the notes. Page 5 of 12

Ensure patients are monitored for suicidal behaviour, self-harm or hostility by the prescribing doctor and the professional delivering the psychological therapy, particularly at the beginning of treatment. If one is needed, use a recognised self-report rating scale such as the MFQ. 5 Treatment with fluoxetine The starting dose should be 10 mg daily, increased if necessary to 20 mg daily after 1 week. Consider lower doses for children of lower body weight. There is little evidence regarding the effectiveness of doses of fluoxetine higher than 20 mg daily, but higher doses may be considered in older children of higher body weight and/or when, in severe illness, an early clinical response is considered a priority. 6 Depression is unresponsive to fluoxetine plus psychological therapy No additional information 7 Fluoxetine is declined No additional information 8 Multidisciplinary review If depression is unresponsive to combined treatment with a specific psychological therapy and fluoxetine after a further 6 sessions, or the patient or parent(s)/carer(s) have declined offer of fluoxetine, make a full needs and risk assessment: review the diagnosis examine the possibility of comorbid diagnoses reassess the possible individual, family and social causes of depression consider whether there has been a fair trial of treatment assess for further psychological therapy for the patient and/or additional help for the family. Page 6 of 12

Psychological therapy Following multidisciplinary review, consider: an alternative psychological therapy which has not been tried (individual CBT, IPT or shorter-term family therapy for at least 3 months), or systemic family therapy (at least 15 fortnightly sessions), or individual child psychotherapy (approximately 30 weekly sessions). Providing psychological therapies for children and young people Ensure psychological therapies are provided by: therapists who are also trained child and adolescent mental healthcare professionals healthcare professionals who have been trained to an appropriate level of competence in the therapy being offered. Develop a joint treatment alliance with the family. If this proves difficult consider providing the family with an alternative therapist. 9 When to consider treatment with sertraline or citalopram If fluoxetine is unsuccessful or not tolerated, consider the use of another antidepressant (sertraline or citalopram are the recommended second-line treatments 1 ). Dose The starting dose of antidepressants other than fluoxetine should be half the daily starting dose for adults, increased if necessary to the daily adult dose gradually over 2 to 4 weeks. Consider lower doses in children of lower body weight. There is little evidence regarding the effectiveness of upper daily adult doses in children and young people, but these may be considered in older children of higher body weight and/or when, in severe illness, an early clinical response is considered a priority. Special considerations for using sertraline and citalopram Only use when the following criteria have been met: The patient and parent(s)/carer(s) have been fully involved in discussions about the benefits and risks. Page 7 of 12

The patient and parent(s)/carer(s) have been provided with appropriate written information covering: rationale for drug treatment delay in onset of effect time course of treatment possible side effects need to take medication as prescribed the latest patient information advice from the relevant regulatory authority. The depression is sufficiently severe and/or causing sufficiently serious symptoms (e.g. weight loss or suicidal behaviour) to justify trial of another antidepressant. There is clear evidence of a fair trial of fluoxetine with a psychological therapy (in other words that all efforts have been made to ensure adherence to the recommended treatment regimen). There has been a reassessment of the likely causes of the depression and of treatment resistance (for example, other diagnoses such as bipolar disorder or substance abuse). There has been advice from a senior child and adolescent psychiatrist (usually a consultant). The child/young person and/or someone with parental responsibility (or the young person alone, if over 16 or deemed competent) has signed an appropriate and valid consent form. 10 Length of treatment and discontinuing medication Length of treatment After remission (no symptoms and full functioning for at least 8 weeks) continue medication for at least 6 months (after the 8-week period). Discontinuing medication Phase out antidepressant medication over 6 12 weeks with the exact dose being titrated against the level of discontinuation/withdrawal symptoms. 1 At the time this pathway was created (May 2011) sertraline and citalopram did not have UK marketing authorisation for use in depression in children and adolescents under the age of 18 years. Check the summary of product characteristics of each drug for current licensed indications. Unlicensed medicines can be legally prescribed where there are no suitable alternatives and where the use is justified by a responsible body of professional opinion (Royal College of Paediatrics and Child Health, 2000; reissued in 2010; also see the NICE guideline on depression in children and young people). Page 8 of 12

Glossary CAMHS child and adolescent mental health services CAPA child and adolescent psychiatric assessment CBT cognitive behavioural therapy CCBT computerised cognitive behavioural therapy DSM-IV diagnostic and Statistical Manual of Mental Disorders ECT electroconvulsive therapy HoNOSCA Health of the Nation Outcome Scales for Children and Adolescents ICD-10 International Statistical Classification of Diseases and Related Health Problems (tenth edition) IPT interpersonal therapy K-SADS schedule for affective disorders and schizophrenia for school-age children Page 9 of 12

MAOI monoamine oxidase inhibitor MFQ mood and feelings questionnaire Mild depression few, if any, symptoms of depression in excess of the 5 required to make the diagnosis, and symptoms result in only minor functional impairment, according to DSM-IV Moderate depression symptoms of depression or functional impairment are between mild and severe NSAID non-steroidal anti-inflammatory drug PCT primary care trust SDQ strengths and difficulties questionnaire Severe depression most symptoms of depression according to DSM-IV, and the symptoms markedly interfere with functioning. Can occur with or without psychotic symptoms SSRI selective serotonin reuptake inhibitor Subthreshold depressive symptoms fewer than 5 symptoms according to DSM-IV Page 10 of 12

TCA tricyclic antidepressant Tier 1 primary care services including GPs, paediatricians, health visitors, school nurses, social workers, teachers, juvenile justice workers, voluntary agencies and social services Tier 2 child and adolescent mental health services relating to workers in primary care including clinical child psychologists, paediatricians with specialist training in mental health, educational psychologists, child and adolescent psychiatrists, child and adolescent psychotherapists, counsellors, community nurses/nurse specialists and family therapists Tier 3 specialised child and adolescent mental health services for more severe, complex or persistent disorders including child and adolescent psychiatrists, clinical child psychologists, nurses (community or inpatient), child and adolescent psychotherapists, occupational therapists, speech and language therapists, art, music and drama therapists, and family therapists Tier 4 tertiary-level child and adolescent mental health services such as day units, highly specialised outpatient teams and inpatient units Sources Depression in children and young people (2005 updated 2015) NICE guideline CG28 Your responsibility The guidance in this pathway represents the view of NICE, which was arrived at after careful consideration of the evidence available. Those working in the NHS, local authorities, the wider public, voluntary and community sectors and the private sector should take it into account when carrying out their professional, managerial or voluntary duties. Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are Page 11 of 12

reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Copyright Copyright National Institute for Health and Care Excellence 2016. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE. Contact NICE National Institute for Health and Care Excellence Level 1A, City Tower Piccadilly Plaza Manchester M1 4BT www.nice.org.uk nice@nice.org.uk 0845 003 7781 Page 12 of 12