Selective serotonin reuptake inhibitors (SSRIs) in childhood depression

NICE state: (1)

• children and young people presenting with moderate to severe depression should be reviewed by a CAMHS team (1)
  
  
• antidepressant medication should not be offered to a child or young person with moderate to severe depression except in combination with a concurrent psychological therapy
  
  
• combined therapy (fluoxetine and psychological therapy) should be considered for initial treatment of moderate to severe depression in young people (12-18 years), as an alternative to psychological therapy followed by combined therapy
  
  
• if psychological therapy as initial treatment
  • following multidisciplinary review, offer fluoxetine if moderate to severe depression in a young person (12-18 years) is unresponsive to a specific psychological therapy after 4 to 6 sessions
  • following multidisciplinary review, cautiously consider fluoxetine 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
• if an antidepressant is to be prescribed this should only be following assessment and diagnosis by a child and adolescent psychiatrist
  
  
• when an antidepressant is prescribed to a child or young person with moderate to severe depression, it should be fluoxetine as this is the only antidepressant for which clinical trial evidence shows that the benefits outweigh the risks
  
  
• when fluoxetine is prescribed for a child or young person with depression, the starting dose should be 10 mg daily
  • can be increased to 20 mg daily after 1 week if clinically necessary, although lower doses should be considered in children of lower body weight
  • little evidence regarding the effectiveness of doses higher than 20 mg daily. However, 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
    
    
• when a child or young person responds to treatment with fluoxetine, medication should be continued for at least 6 months after remission (defined as no symptoms and full functioning for at least 8 weeks); in other words, for 6 months after this 8-week period
  
  
• if treatment with fluoxetine is unsuccessful or is not tolerated because of side effects, consideration should be given to the use of another antidepressant. In this case sertraline or citalopram are the recommended second-line treatments
  • when a child or young person responds to treatment with citalopram or sertraline, medication should be continued for at least 6 months after remission (defined as no symptoms and full functioning for at least 8 weeks)
    
    
• paroxetine and venlafaxine should not be used for the treatment of depression in children and young people
  
  
• tricyclic antidepressants should not be used for the treatment of depression in children and young people
  
  
• where antidepressant medication is to be discontinued, the drug should be phased out over a period of 6 to 12 weeks
  • exact dose being titrated against the level of discontinuation/withdrawal symptoms
    

Tricyclic antidepressants

• previously used to treat depression in children
• little study evidence of benefit in adolescents and children (2)
• not approved by NICE

A systematic review suggests that most selective serotonin reuptake inhibitors lead to adverse events that appear to outweigh the benefits in children (5)

• the review notes that fluoxetine improves symptoms without increasing adverse events
  • for paroxetine, sertraline, venlafaxine and citalopram, the risks outweigh the benefits

Cochrane review found that fluoxetine was the only agent with consistent evidence that it is effective in decreasing depressive symptoms (9)

Treatment should begin at the lowest dosage available and titrated according to the patient's response and adverse effects (3,4)

• if initial first-line therapy is ineffective, another first-line agent should be considered (3,4)
• close monitoring is recommended (e.g., weekly telephone calls, scheduled visits for the first month of therapy) to assess for suicidality and other adverse effects, such as gastrointestinal effects, nervousness, headache, and restlessness (3,4)
  

Suicide risk and SSRIs in children and adolescence

• there is inconsistent evidence of an increased rate of suicide-related events and intentional self-harm associated with SSRIs (5)
  • data from randomised controlled trials in adolescents and young adults report an increased risk of suicide-related events (6)
• results from these trials should be interpreted with caution, as they were not primarily designed to measure suicide-related events and it would be unethical to do so using placebo as a control (6,7)
• study evidence has shown (8) no systematic differences between the association of TCAs and SSRIs and the incidence risk ratios for attempted suicide, suicidal ideation or intentional self-harm and, apart from the day of prescription, rates did not exceed pre-exposure levels. The pattern of Incidence Rate Ratios for suicide for SSRIs was similar to that found in non-fatal suicide-related events (8)
  

Treatment Duration

• treatment of depression in children and adolescents should continue for six months after remission (3,4)

Reference:

• 1) NICE (June 2019). Depression in children and young people.
• 2) Hazell P, O'Connell D, Heathcote D, Henry D. Tricyclic drugs for depression in children and adolescents Cochrane Database Syst Rev. 2002(2):CD002317.
• 3) Hughes CW, Emslie GJ, Crismon ML, et al. Texas Children's Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(6):667-686.
• 4) Cheung AH, Zuckerbrot RA, Jensen PS, Ghalib K, Laraque D, Stein RE; GLAD-PC Steering Group. Guidelines for adolescent depression in primary care (GLAD-PC): II. Treatment and ongoing management. Pediatrics. 2007;120(5):e1313-e1326
• 5) Whittington CJ et al (2004). Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet;363:1341-5
• 6) Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006;63:332-9
• 7) Rothman KJ, Michels KB. The continuing unethical use of placebo controls. N Engl J Med 1994;331:394-8
• 8) Wijlaars LP et al. Suicide-related events in young people following prescription of SSRIs and other antidepressants: a self-controlled case series analysis. BMJ Open. 2013 Sep 19;3(9):e003247.
• 9) Hetrick S, Merry S, McKenzie J, Sindahl P, Proctor M. Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents Cochrane Database Syst Rev. 2007(3):CD004851.