Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

at risk of suicidality

1st line – risk-tailored suicide mitigation

Back
INITIAL
|
at risk of suicidality
1st line – 

risk-tailored suicide mitigation

Children and adolescents experiencing suicidal ideation, particularly those who have suicidal ideation and a history of suicide attempts, require safety planning.[68]​ Safety planning is an intervention carried out in collaboration between the patient and a health care professional, for example, therapist or care manager, that encompasses helping the patient identify their risk factors for suicidal ideation as well as a series of supports that they can draw on to reduce their risk of self-harm.[68]​ Part of the safety plan involves helping the patient be aware of local crisis support services and ideally would involve caregivers in its development.

It is imperative to ask about access to lethal means (firearms, medications, illicit substances, knives, ropes) when suicidal ideation or a plan is disclosed, followed by risk-tailored counseling and mitigation.[68][70]

When considering confidentiality and its limitations, it is important to note that recent or active suicidal ideation (including suicide attempts) must always be communicated to a responsible adult in order to protect the patient from harm, and to involve the caregiver in necessary treatment.[68]​ Ideally, and if at all possible, this should be done with the consent of the patient. Confidentiality and its limitations, for example, when a breach of confidentiality is required in order to protect the patient and/or public safety, can be a challenging area and requires clinical judgment, as well as knowledge of local/state/national legal frameworks; external advice from an ethics or risk management specialist may be beneficial.

Children and adolescents who are depressed with severe suicidality without being able to maintain safety, or with significant psychosis, require urgent referral to the emergency room.

Hospitalization may be necessary to carry out an urgent mental healthcare assessment; ensure safety for the patient and/or for others; and stabilize the patient.[63]

See: Suicide risk mitigation.

ACUTE

mild

1st line – active monitoring + supportive care

Back
ACUTE
|
mild
1st line – 

active monitoring + supportive care

For mild or brief uncomplicated depression, a brief period of up to 6 weeks of active monitoring, with supportive care including psychoeducation for the child and parents, may be appropriate.[67]​​​[86][87][91]​​ Mild depression often resolves with nonspecific treatment.

A lifestyle assessment, and recommendations for changes in diet and exercise, may facilitate treatment and achieve better outcomes. Several controlled studies have demonstrated that exercise has an efficacy comparable with antidepressant therapy, and superior efficacy compared with placebo, in reducing depressive symptoms in adults, but pediatric evidence is still limited.[92]

A meta-analysis of randomized controlled trials of exercise (4 trials, 159 participants) confirmed previous reviews by finding a medium-sized treatment effect (effect size -0.59, 95% CI -1.08 to -0.10) favoring exercise, but the investigators cautioned there was a high risk of bias in the included studies.[94] Another meta-analysis that included both randomized and nonrandomized trials of exercise (10 trials, 431 participants) found a small- to medium-sized effect in reducing symptoms (effect size -0.49, 95% CI -0.71 to -0.24), but again the authors cautioned that the quality of included studies was low.[95]

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, immediate treatment and high levels of care (e.g., inpatient treatment) may be required.

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
mild
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with mild depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a long time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

2nd line – specific psychotherapy + supportive care

Back
ACUTE
|
mild
2nd line – 

specific psychotherapy + supportive care

If the response to active monitoring is inadequate, a course of specific evidence-based psychotherapy, such as cognitive behavioral therapy (CBT; including digital CBT) or interpersonal psychotherapy, if available and appropriate, may be used.[67]​​[97][98]

In the UK, the National Institute for Health and Care Excellence guidelines recommend the consideration of attachment-based family therapy for children with depression continuing after a period of watchful waiting.[67]​​

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, immediate treatment and high levels of care (e.g., inpatient treatment) may be required.

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
mild
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with mild depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so some patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression, and also a frequent residual symptom.[96]​​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

moderate or severe

1st line – selective serotonin-reuptake inhibitor (SSRI) + supportive care

Back
ACUTE
|
moderate or severe
1st line – 

selective serotonin-reuptake inhibitor (SSRI) + supportive care

For moderate or severe depression, antidepressant treatment with an SSRI may be initiated. [ Cochrane Clinical Answers logo ]

The SSRI fluoxetine is the treatment of first choice based on meta-analysis data, although note that treatment effects may vary between individuals, and so individualized risk:benefit analysis is required when selecting an SSRI.[105][106][107][108]​​​​​ In particular, fluoxetine it is preferable over other SSRIs when time to remission is a high priority, and can be complemented by regular risk assessment in regards to suicidality by any professional. Psychological therapy is the treatment of first choice when maintaining safety is a high priority. This is salient when a young person with major depressive disorder has prominent suicide ideation, or has engaged in self-harm.

The results of one meta-analysis suggest that SSRIs are more beneficial than placebo for treating children and adolescents with depression, although the effect size is small. The placebo effect appears to play a significant role in the efficacy of SSRIs. Children and adolescents treated with SSRIs reported a greater incidence of adverse effects than those treated with placebo, including serious adverse effects such as suicidality, emphasizing the need for a careful and individualized harm-benefit analysis prior to treatment.[109]

When discussing the use of an SSRI for treatment of depression, it is important to set realistic expectations for the child and caregiver. Not all children with depression will respond to an SSRI. Response, if positive, is subtle and gradual and requires physician monitoring. Not all depressive symptoms will respond to an SSRI; thus, it is important to consider adjunct interventions, mostly environmental, for those symptoms (e.g., sleep and pleasurable activity scheduling, appropriate nutrition and exercise, and classroom accommodations). In addition, when starting medication, ensure the caregiver appreciates the importance of monitoring the administration and safe-keeping of medication.

The Food and Drug Administration (FDA) has issued warnings that use of antidepressant medications poses a small, but significantly increased, risk of suicidal ideation or suicide behavior for children and adolescents.

A minimum of 1 to 2 visits every 4 weeks during the initial months of antidepressant treatment is required, although, in the US, the FDA recommends weekly visits during the first month after initiating an antidepressant, and biweekly visits during the second and third months of therapy.

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, high levels of care (e.g., inpatient treatment) may be required.

Doses and age cut-offs stated here may be off-label in some countries; consult your local guidance. These drugs are only to be prescribed by a specialist experienced in the treatment of pediatric psychiatric disorders in those countries. Guidelines for prescribing are available for North America and the UK.[67]​​​[86][91]​​

Primary options

fluoxetine: children <8 years of age: consult specialist for guidance on dose; children ≥8 years of age: 10 mg orally once daily initially, increase according to response, maximum 60 mg/day

OR

escitalopram: children <12 years of age: consult specialist for guidance on dose; children ≥12 years of age: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day

OR

sertraline: children <10 years of age: consult specialist for guidance on dose; children ≥10 years of age: 25 mg orally once daily initially, increase according to response, maximum 200 mg/day

OR

citalopram: children <7 years of age: consult specialist for guidance on dose; children ≥7 years of age: 10 mg orally once daily initially, increase according to response, maximum 40 mg/day (20 mg/day in poor metabolizers of CYP2C19)

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
moderate or severe
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​​​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

1st line – psychotherapy + supportive care

Back
ACUTE
|
moderate or severe
1st line – 

psychotherapy + supportive care

Specific psychotherapies may also be used for children and young people with depression of moderate or greater severity as first-line treatment.[100]

UK guidelines recommend an initial trial of psychotherapy for all young people with depression of moderate or greater severity. US guidelines recommend either specific psychotherapies, medication, or their combination for young people with depression of moderate or greater severity.[86]

Specific psychotherapies can include cognitive behavioral therapy, interpersonal psychotherapy, and dialectical behavioral therapy.[67]​​

The importance of concurrent or first-line psychotherapy is supported by long-term results and safety outcomes. Results from one study indicate that combination therapy may decrease suicidal ideation more than medication alone.[103]

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, high levels of care (e.g., inpatient treatment) may be required.

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
moderate or severe
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

1st line – selective serotonin-reuptake inhibitor (SSRI) + psychotherapy + supportive care

Back
ACUTE
|
moderate or severe
1st line – 

selective serotonin-reuptake inhibitor (SSRI) + psychotherapy + supportive care

US guidelines recommend either specific psychotherapies, medication, or their combination for young people with depression of moderate or greater severity.[86] UK guidelines recommend an initial trial of psychotherapy for all young people with depression of moderate or greater severity. Antidepressants are recommended only in combination with psychotherapy and generally after a trial of psychotherapy; however, combined therapy with fluoxetine and psychotherapy may be considered for initial treatment of moderate to severe depression in young people ages 12 to 18 years.[67]​​

The SSRI fluoxetine is the treatment of first choice based on meta-analysis data, although note that treatment effects may vary between individuals, and so individualized risk:benefit analysis is required when selecting an SSRI.[105][106][107][108]​​​ In particular, fluoxetine is preferable over other SSRIs when time to remission is a high priority, and can be complemented by regular risk assessment in regards to suicidality by any professional. Psychological therapy is the treatment of first choice when maintaining safety is a high priority. This is salient when a young person with major depressive disorder has prominent suicide ideation, or has engaged in self-harm.

The importance of concurrent or first-line psychotherapy is supported by long-term results and safety outcomes. Combination therapy may decrease suicidal ideation more than medication alone.[103] In a meta-analysis of combined medication and psychotherapy versus medication alone, there was greater improvement in global functioning with combination treatment, but no difference was reported between the groups on depressive symptom reduction.[104]

The results of one meta-analysis suggest that SSRIs are more beneficial than placebo for treating children and adolescents with depression, although the effect size is small. The placebo effect appears to play a significant role in the efficacy of SSRIs. Children and adolescents treated with SSRIs reported a greater incidence of adverse effects than those treated with placebo, including serious adverse effects such as suicidality, emphasizing the need for a careful and individualized harm-benefit analysis prior to treatment.[109]

When discussing the use of an SSRI for treatment of depression, it is important to set realistic expectations for the child and caregiver. Not all children with depression will respond to an SSRI. Response, if positive, is subtle and gradual and requires physician monitoring. Not all depressive symptoms will respond to an SSRI; thus, it is important to consider adjunct interventions, mostly environmental, for those symptoms (e.g., sleep and pleasurable activity scheduling, appropriate nutrition and exercise, and classroom accommodations). In addition, when starting medication, ensure the caregiver appreciates the importance of monitoring the administration and safe-keeping of medication.

A minimum of 1 to 2 visits every 4 weeks during the initial months of antidepressant treatment is required.

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, high levels of care (e.g., inpatient treatment) may be required.

Doses and age cut-offs stated here may be off-label in some countries; consult your local guidance. These drugs are only to be prescribed by a specialist experienced in the treatment of pediatric psychiatric disorders in those countries. Guidelines for prescribing are available for North America and the UK.[66][67]​​​​[86]

Primary options

fluoxetine: children <8 years of age: consult specialist for guidance on dose; children ≥8 years of age: 10 mg orally once daily initially, increase according to response, maximum 60 mg/day

OR

escitalopram: children <12 years of age: consult specialist for guidance on dose; children ≥12 years of age: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day

OR

sertraline: children <10 years of age: consult specialist for guidance on dose; children ≥10 years of age: 25 mg orally once daily initially, increase according to response, maximum 200 mg/day

OR

citalopram: children <7 years of age: consult specialist for guidance on dose; children ≥7 years of age: 10 mg orally once daily initially, increase according to response, maximum 40 mg/day (20 mg/day in poor metabolizers of CYP2C19)

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
moderate or severe
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

2nd line – switch to a different selective serotonin-reuptake inhibitor (SSRI) + psychotherapy + supportive care

Back
ACUTE
|
moderate or severe
2nd line – 

switch to a different selective serotonin-reuptake inhibitor (SSRI) + psychotherapy + supportive care

If, after 8 weeks of treatment with an SSRI at an adequate dose, there is no response (no change in depression severity or functioning impairment), or only partial response (less than a significant reduction of depression severity or improvement of functioning), switching to another SSRI is recommended, as well as the addition of cognitive behavioral therapy.

The results of one meta-analysis suggest that SSRIs are more beneficial than placebo for treating children and adolescents with depression, although the effect size is small. The placebo effect appears to play a significant role in the efficacy of SSRIs. Children and adolescents treated with SSRIs reported a greater incidence of adverse effects than those treated with placebo, including serious adverse effects such as suicidality, emphasizing the need for a careful and individualized cost-benefit analysis prior to treatment.[109]

When discussing the use of an SSRI for treatment of depression, it is important to set realistic expectations for the child and caregiver. Not all children with depression will respond to an SSRI. Response, if positive, is subtle and gradual and requires physician monitoring. Not all depressive symptoms will respond to an SSRI; thus, it is important to consider adjunct interventions, mostly environmental, for those symptoms (e.g., sleep and pleasurable activity scheduling, appropriate nutrition and exercise, and classroom accommodations). In addition, when starting medication, ensure the caregiver appreciates the importance of monitoring the administration and safe-keeping of medication.

The Food and Drug Administration (FDA) has issued warnings that the use of antidepressant medications poses a small, but significantly increased, risk of suicidal ideation or suicide attempts for children and adolescents.

A minimum of 1 to 2 visits every 4 weeks during the initial months of antidepressant treatment is required, although, in the US, the FDA recommends weekly visits during the first month after initiating an antidepressant, and biweekly visits during the second and third months of therapy.

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, high levels of care (e.g., inpatient treatment) may be required.

Doses and age cut-offs stated here may be off-label in some countries; consult your local guidance. These drugs are only to be prescribed by a specialist experienced in the treatment of pediatric psychiatric disorders in those countries. Guidelines for prescribing are available for North America and the UK.​​[66][67]​​​​[86]

Primary options

fluoxetine: children <8 years of age: consult specialist for guidance on dose; children ≥8 years of age: 10 mg orally once daily initially, increase according to response, maximum 60 mg/day

OR

escitalopram: children <12 years of age: consult specialist for guidance on dose; children ≥12 years of age: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day

OR

sertraline: children <10 years of age: consult specialist for guidance on dose; children ≥10 years of age: 25 mg orally once daily initially, increase according to response, maximum 200 mg/day

OR

citalopram: children <7 years of age: consult specialist for guidance on dose; children ≥7 years of age: 10 mg orally once daily initially, increase according to response, maximum 40 mg/day (20 mg/day in poor metabolizers of CYP2C19)

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
moderate or severe
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

3rd line – switch to a non-selective serotonin-reuptake inhibitor + psychotherapy + supportive care

Back
ACUTE
|
moderate or severe
3rd line – 

switch to a non-selective serotonin-reuptake inhibitor + psychotherapy + supportive care

At this stage it is important to reassess the patient in order to verify the diagnosis, and to rule out other contributing factors, such as unrecognized or newly emergent comorbid illness (e.g., substance use disorder), inadequacy of psychosocial intervention, unresolved stress, or a new trauma.

Switching to an antidepressant that is not an SSRI is recommended if a second SSRI produces minimal to no response. Choices for switching include mirtazapine, bupropion, and venlafaxine. These agents should only be commenced by specialists who are experts in managing depression in childhood. UK guidelines recommend that venlafaxine should not be used for the treatment of depression in children and young people.[67]​​

The results of one meta-analysis suggest that serotonin–norepinephrine reuptake inhibitors (SNRIs) are more beneficial than placebo for treating children and adolescents with depression, although the effect size is small. The placebo effect appears to play a significant role in the efficacy of SNRIs. Children and adolescents treated with SNRIs reported a greater incidence of adverse effects than those treated with placebo, including serious adverse effects such as suicidality, emphasizing the need for a careful and individualized cost-benefit analysis prior to considering treatment.[109]

Venlafaxine did have significantly more suicide-related adverse events than placebo in one assessment.[122]

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, high levels of care (e.g., inpatient treatment) may be required.

These drugs are only to be prescribed by a specialist experienced in the treatment of pediatric psychiatric disorders in those countries. Guidelines for prescribing are available for North America and the UK.​​[66][67]​​​[86]

Primary options

mirtazapine: consult specialist for guidance on dose

OR

bupropion hydrochloride: consult specialist for guidance on dose

OR

venlafaxine: consult specialist for guidance on dose

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
moderate or severe
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

4th line – augmentation of second selective serotonin-reuptake inhibitor (SSRI) with psychotherapy or with another medication + supportive care

Back
ACUTE
|
moderate or severe
4th line – 

augmentation of second selective serotonin-reuptake inhibitor (SSRI) with psychotherapy or with another medication + supportive care

At this stage it is important to reassess the patient in order to verify the diagnosis, and to rule out other contributing factors, such as unrecognized or newly emergent comorbid illness (e.g., substance use disorder), inadequacy of psychosocial intervention, unresolved stress, or a new trauma.

As an alternative to switching to an antidepressant that is not a SSRI, it is possible to augment the existing SSRI with either psychotherapy or another medication.

Atypical antipsychotics and bupropion have been used more frequently in the pediatric population as augmenting agents, compared with other agents. However, pediatric controlled studies have not been done. These agents should only be commenced by specialists who are experts in managing depression in childhood.

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, high levels of care (e.g., inpatient treatment) may be required.

Doses and age cut-offs stated here may be off-label in some countries; consult your local guidance. These drugs are only to be prescribed by a specialist experienced in the treatment of pediatric psychiatric disorders in those countries. Guidelines for prescribing are available for North America and the UK.​​[66][67]​​​[86]

Primary options

fluoxetine: children <8 years of age: consult specialist for guidance on dose; children ≥8 years of age: 10 mg orally once daily initially, increase according to response, maximum 60 mg/day

or

escitalopram: children <12 years of age: consult specialist for guidance on dose; children ≥12 years of age: 10 mg orally once daily initially, increase according to response, maximum 20 mg/day

or

sertraline: children <10 years of age: consult specialist for guidance on dose; children ≥10 years of age: 25 mg orally once daily initially, increase according to response, maximum 200 mg/day

or

citalopram: children <7 years of age: consult specialist for guidance on dose; children ≥7 years of age: 10 mg orally once daily initially, increase according to response, maximum 40 mg/day (20 mg/day in poor metabolizers of CYP2C19)

-- AND --

bupropion hydrochloride: consult specialist for guidance on dose

or

quetiapine: consult specialist for guidance on dose

or

aripiprazole: consult specialist for guidance on dose

or

ziprasidone: consult specialist for guidance on dose

or

risperidone: consult specialist for guidance on dose

or

olanzapine: consult specialist for guidance on dose

or

lamotrigine: consult specialist for guidance on dose

or

lithium: consult specialist for guidance on dose

Consider – management of associated symptoms and comorbid disorders

Back
ACUTE
|
moderate or severe
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

5th line – novel alternative approaches + supportive care

Back
ACUTE
|
moderate or severe
5th line – 

novel alternative approaches + supportive care

If response remains poor, despite all of the possible treatments outlined up to this phase, novel alternative treatments may be considered. These should only be commenced by specialists who are experts in managing depression in childhood.

Other antidepressants, such as tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs), may be used for children and adolescents who have not responded to SSRIs or non-SSRIs. TCAs have not been shown to be effective in treating pediatric depression, and tend to produce more adverse events.[143] [ Cochrane Clinical Answers logo ] UK guidelines recommend that TCAs should not be used for the treatment of depression in children and young people.[67]​ Because of the adverse effects and difficulty of managing diet in children and adolescents, MAOIs have not been recommended for use in pediatric depression.

Biological treatments include light therapy and electroconvulsive therapy (ECT). There have not been any controlled trials of ECT conducted in the pediatric population. In several US states, ECT in children and adolescents has been banned.

If there is an acute progression of symptoms and depression becomes severe, or if suicidality or psychosis develops, high levels of care (e.g., inpatient treatment) may be required.

Consider – management of associated symptoms and comorbid disorders

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ACUTE
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moderate or severe
Consider – 

management of associated symptoms and comorbid disorders

Treatment recommended for SOME patients in selected patient group

Comorbid disorders: this is an important consideration at all steps of treatment. Anxiety disorders and ADHD are common comorbid disorders. Psychotherapy for an anxiety disorder may be started concomitantly with antidepressant treatment. However, it is not recommended to start both an antidepressant and another medication to treat a comorbid disorder simultaneously. The primary illness, or the disorder causing the most impairment of function, needs to be treated first. Then, sequentially, a second and third treatment to target comorbid disorders may be initiated if required (e.g., a stimulant may be started sequentially with an antidepressant).

Associated symptoms: typically, adjunctive medications are instituted to manage symptoms associated with depression (e.g., agitation) and are discontinued when the target symptom resolves. Adjunctive therapy may be required in any of the treatment steps for depression of all severities. Some depressive symptoms (e.g., agitation) may take a longer time to resolve, so certain patients may need adjunctive treatment early on during the acute treatment phase.

Insomnia is a frequent symptom of depression and also a frequent residual symptom.[96]​ Using an evidence-based psychosocial intervention such as cognitive behavioral therapy for insomnia (CBT-I) may be helpful to resolve insomnia early during acute treatment. Occasionally, medication in combination with behavioral therapy may be considered for children and adolescents whose insomnia is unresponsive to behavioral interventions. Clinicians should consult local service models, but typically consideration of medication for insomnia in children requires referral to a pediatric sleep clinic or other specialist setting.

ONGOING

following stabilization of acute symptoms

1st line – continuation therapy for 6 to 12 months

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ONGOING
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following stabilization of acute symptoms
1st line – 

continuation therapy for 6 to 12 months

Once remission is achieved, whether it is after the first medication or psychotherapy treatment or after multiple treatment trials, treatment is continued for 6 to 12 months to avoid relapse, at the same dose used for acute treatment. Recommendation is 6 months for first episode, 12 months for recurrent episode.

Consider – maintenance therapy for 1 to 2 years

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ONGOING
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following stabilization of acute symptoms
Consider – 

maintenance therapy for 1 to 2 years

Treatment recommended for SOME patients in selected patient group

Following the period of continuation therapy, 1 to 2 years of maintenance treatment may be needed for children who are at risk of having recurrent depression (multiple episodes, chronic depression, comorbid disorders).

One small pediatric depression maintenance study has been reported.[90] Although a larger study is needed, maintenance treatment is recommended by treatment guidelines.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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