Depressive disorders are characterized by sadness or irritability that is severe or persistent enough to interfere with functioning or cause considerable distress. Diagnosis is based on clinical criteria. Treatment is with antidepressants, supportive and cognitive-behavioral therapy, or a combination of these modalities.
(See also discussion of Depressive Disorders in adults.)
Depressive disorders in children and adolescents include
Disruptive mood dysregulation disorder
Major depressive disorder
Persistent depressive disorder (dysthymia)
Other specified depressive disorder
The term depression is often loosely used to describe the low or discouraged mood that results from disappointment (eg, serious illness) or loss (eg, death of a loved one). However, such low moods, unlike depression, occur in waves that tend to be tied to thoughts or reminders of the triggering event, resolve when circumstances or events improve, may be interspersed with periods of positive emotion and humor, and may not be accompanied by pervasive feelings of worthlessness and self-loathing. The low mood usually lasts days rather than weeks or months, and suicidal thoughts and prolonged loss of function are much less likely. Such low moods are more appropriately called demoralization or grief. However, events and stressors that trigger demoralization and grief can also precipitate a major depressive episode.
Depression is commonly reported in children and adolescents and its prevalence increases with age. In a global sample, the peak age of onset was 15.5 years, with 10% experiencing first symptoms by age 14, 26% by age 18, and 47% by age 25 (1). In another meta-analysis, the global lifetime prevalence of moderate–severe depression was 19% (2). However, the prevalence of major depression was lower at 4%% (3). Females are affected almost twice as commonly as males.
General references
1. Solmi M, Radua J, Olivola M, et al. Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies. Mol Psychiatry. 2022;27(1):281-295. doi:10.1038/s41380-021-01161-7
2. Shorey S, Ng ED, Wong CHJ. Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta-analysis. Br J Clin Psychol. 2022;61(2):287-305. doi:10.1111/bjc.12333
3. Lu B, Lin L, Su X. Global burden of depression or depressive symptoms in children and adolescents: A systematic review and meta-analysis. J Affect Disord. 2024;354:553-562. doi:10.1016/j.jad.2024.03.074
Etiology of Depressive Disorders
The etiology of depression in children and adolescents is less clearly understood as in adults, but is expected to share broad similarities; it is believed in part to result from interactions of genetically determined risk factors and environmental stress (particularly early life stress such as abuse, injury, natural disaster, domestic violence, death of family member, and deprivation [1]).
Among other factors, the quality and quantity (ie, time spent) of use of social media and social networking sites have raised concerns because their use leads to decreased face-to-face interpersonal interactions, addiction-like behaviors, online bullying, and social pressure from increased social comparisons (2). Depression itself has been associated with problematic internet use. However, moderate use, especially when used to acquire knowledge, may support emotional regulation and development.
During the COVID-19 pandemic, depression symptoms doubled in youths, especially in females and older adolescents (3).Mental health care visits for depression, as well as anxiety, both increased by 43%, compared to before the pandemic (4). Children (ages 5 to 11) who had a documented COVID-19 infection had greater risk for bipolar disorder, and adolescents had greater risk for minor depression, when compared to controls exposed to the pandemic stress without evidence of infection (5).
Etiology references
1. LeMoult J, Humphreys KL, Tracy A, et al. Meta-analysis: Exposure to early life stress and risk for depression in childhood and adolescence. J Am Acad Child Adolesc Psychiatry. 59(7);842-855, 2020. doi: https://doi.org/10.1016/j.jaac.2019.10.011
2. Vidal C, Lhaksampa T, Miller L, Platt R. Social media use and depression in adolescents: a scoping review. Int Rev Psychiatry. 2020;32(3):235-253. doi:10.1080/09540261.2020.1720623
3. Racine N, McArthur B, Cooke J, et al. Global prevalence of depressive and anxiety symptoms in children and adolescence during COVID-19: A meta-analysis. JAMA Pediatr. 175(11):1142-1150, 2021. doi: 10.1001/jamapediatrics.2021.2482
4. Dvir Y, Ryan C, Straus JH. Comparison of use of the Massachusetts Child Psychiatry Access Program and patient characteristics before vs during the COVID-19 pandemic. JAMA Netw Open.5(2):e2146618, 2022. doi:10.1001/jamanetworkopen.2021.46618
5. Lu Y, Tong J, Zhang D, et al. Risk of neuropsychiatric and related conditions associated with SARS-CoV-2 infection: a difference-in-differences analysis. Nat Commun. 2025;16(1):6829. Published 2025 Jul 24. doi:10.1038/s41467-025-61961-1
Pathophysiology of Depressive Disorders
Mechanisms contributing to depression in childhood and adolescence remain poorly characterized, but may in part be attributed to a combination of genetic predisposition, a dysregulation in neurotransmitter pathways, and environmental stressors. Disturbances in neurotransmitter systems, particularly in the serotonergic and glutamatergic pathways involving N-methyl-D-aspartate (NMDA) receptors, are crucial to understanding the pathophysiology of depression, as evidenced by the effectiveness of NMDA antagonists like ketamine in treating resistant cases (-aspartate (NMDA) receptors, are crucial to understanding the pathophysiology of depression, as evidenced by the effectiveness of NMDA antagonists like ketamine in treating resistant cases (1). Additionally, abnormal brain activation patterns in areas such as the subgenual anterior cingulate cortex, ventrolateral prefrontal cortex, and thalamus may be present (2). Finally, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is a prominent feature in youth with major depressive disorder, potentially exacerbating emotional dysregulation and contributing to the onset of clinical depression (3).
Pathophysiology references
1. Ferrari F, Villa RF. The Neurobiology of Depression: an Integrated Overview from Biological Theories to Clinical Evidence. Mol Neurobiol. 2017;54(7):4847-4865. doi:10.1007/s12035-016-0032-y
2.Miller CH, Hamilton JP, Sacchet MD, Gotlib IH. Meta-analysis of Functional Neuroimaging of Major Depressive Disorder in Youth. JAMA Psychiatry. 2015;72(10):1045-1053. doi:10.1001/jamapsychiatry.2015.1376
3.Guerry JD, Hastings PD. In search of HPA axis dysregulation in child and adolescent depression. Clin Child Fam Psychol Rev. 2011;14(2):135-160. doi:10.1007/s10567-011-0084-5
Symptoms and Signs of Depressive Disorders
The basic manifestations of depressive disorders in children and adolescents are similar to those in adults but are related to the typical concerns of children, such as schoolwork and play. Younger children may be unable to explain inner feelings or moods. Depression should be considered when previously well-performing children do poorly in school, withdraw from society, or commit delinquent acts. Older children and adolescents are typically able to articulate their symptoms more clearly, which may include low mood, lack of interest in routine and social activities, changes in appetite and weight, problems sleeping, low energy, inability to make decisions, and suicidal ideation or behavior.
In some children with a depressive disorder, the predominant mood is irritability rather than sadness (an important difference between childhood and adult forms). The irritability associated with childhood depression may present as overactivity and aggressive, antisocial behavior.
In children with intellectual disability, depressive or other mood disorders may present as somatic symptoms and behavioral disturbances.
Disruptive mood dysregulation disorder
Disruptive mood dysregulation disorder involves persistent irritability and frequent episodes of behavior that is very out of control, with onset at age 6 to 10 years. Many children also have other disorders, particularly oppositional defiant disorder, attention-deficit/hyperactivity disorder (ADHD), or an anxiety disorder. The diagnosis is not made before age 6 years or after age 18 years. As adults, patients may develop unipolar (rather than bipolar) depression or an anxiety disorder.
Manifestations include the presence of the following for ≥ 12 months (with no period of ≥ 3 months without all of them):
Severe recurrent temper outbursts (eg, verbal rage and/or physical aggression toward people or property) that are grossly out of proportion to the situation and that occur ≥ 3 times/week on average
Temper outbursts that are inconsistent with developmental level
An irritable, angry mood present every day for most of the day and observed by others (eg, parents, teachers, peers)
The outbursts and angry mood must occur in 2 of 3 settings (at home or school, with peers).
Major depressive disorder
Major depressive disorder is a discrete depressive episode lasting ≥ 2 weeks. It occurs in as many as 2.8% of children under the age of 13 and 5.6% of adolescents (1). Major depressive disorder can first occur at any age but is more common after puberty (2), reaching about 11% between the ages of 13 and 18 years (3, 4). Untreated, major depression may remit in 6 to 12 months. The risk of recurrence is higher in patients who have had severe episodes, who are younger, or who have had multiple episodes. Persistence of even mild depressive symptoms during remission is a strong predictor of recurrence.
For diagnosis, ≥ 1 of the following must be present for most of the day nearly every day during the same 2-week period (5):
Depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by others
Loss of interest or pleasure in almost all activities (sometimes expressed as profound boredom)
In addition, ≥ 4 of the following must be present:
Decrease in weight when not dieting (in children, failure to make the expected weight gain), increase in weight, or decrease or increase in appetite
Insomnia or hypersomnia nearly every day
Psychomotor agitation or retardation observed by others (not self-reported)
Fatigue or loss of energy nearly every day
Decreased ability to think, concentrate, and make choices
Recurrent thoughts of death (not just fear of dying) and/or suicidal ideation or plans
Feelings of worthlessness (ie, feeling rejected and unloved) or excessive or inappropriate guilt
Major depression in adolescents is a risk factor for academic failure, substance use, and suicidal behavior. While depressed, children and adolescents tend to fall far behind academically and lose important peer relationships. In very severe depression, psychotic symptoms may emerge.
Persistent depressive disorder (dysthymia)
Dysthymia is a persistent depressed or irritable mood that lasts for most of the day for more days than not for ≥ 1 year plus ≥ 2 of the following:
Poor appetite or overeating
Insomnia or hypersomnia
Low energy or fatigue
Low self-esteem
Poor concentration
Feelings of hopelessness
Symptoms may be less intense than those of a major depressive disorder. Nevertheless, because of the chronicity of this disorder, it can be perceived to be more disabling than major depressive disorder, despite the fact that its symptoms are generally less intense.
A major depressive episode may occur before the onset or during the first year (ie, before the duration criterion is met for persistent depressive disorder).
Other Specified Depressive Disorder refers to the presence of symptoms of a depressive disorder but does not meet full criteria for any of them.
Symptoms and signs references
1. Costello EJ, Erkanli A, Angold A. Is there an epidemic of child or adolescent depression?. J Child Psychol Psychiatry. 2006;47(12):1263-1271. doi:10.1111/j.1469-7610.2006.01682.x
2. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence?. Nat Rev Neurosci. 2008;9(12):947-957. doi:10.1038/nrn2513
3. World Health Organization. Adolescent Mental Health in the European Region: Factsheet for World Mental Health Day 2018; World Health Organization: Geneva, Switzerland, 2018
4. Avenevoli S, Swendsen J, He JP, Burstein M, Merikangas KR. Major depression in the national comorbidity survey-adolescent supplement: prevalence, correlates, and treatment. J Am Acad Child Adolesc Psychiatry. 2015;54(1):37-44.e2. doi:10.1016/j.jaac.2014.10.010
5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision. American Psychiatric Association Publishing; 2022
Diagnosis of Depressive Disorders
Psychiatric assessment
Diagnostic and Statistical Manual of Mental Disorders, Fifth edition, Text Revision (DSM-5-TR) criteria
The diagnosis of depressive disorders is based on symptoms and signs, and specific types may be classified using the DSM-5-TR criteria (1).
Sources of information include an interview with the child or adolescent and information from parents, caregivers, and teachers. Several brief questionnaires are available for screening; commonly used ones in the United States include the Patient Health Questionnaire - Nine Item (PHQ-9) and Beck Depression Inventory (2, 3). (See Depression Assessment Instruments for these and other inventories and assessment tools.) They help identify some depressive symptoms but cannot be used alone for diagnosis. Specific close-ended questions help determine whether patients have the symptoms required for the diagnosis of major depression, based on DSM-5-TR criteria.
History should include related factors such as domestic violence, sexual abuse and exploitation, and adverse drug reactions. It is important to screen for suicidal behavior (eg, ideation, gestures, attempts). It is also important to ask about social media and social networking site use; particularly to track the length of time used and whether use occurs during daytime or nighttime hours. Underlying mood disorders and conditions that can cause anxiety should also be considered.
A careful review of the history and appropriate laboratory tests are needed to exclude other organic disorders (eg, infectious mononucleosis, thyroid disorders, substance use disorders) that can cause similar symptoms.
Other psychiatric disorders that can increase the risk and/or modify the course of depressive symptoms (eg, anxiety and bipolar disorders) must be considered. Some children who eventually develop a bipolar disorder or schizophrenia may present initially with major depression.
After depression is diagnosed, the family and social setting must be further evaluated to identify (and modify) stressors that may have precipitated depression.
Diagnosis references
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision. American Psychiatric Association Publishing; 2022
2. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-613. doi:10.1046/j.1525-1497.2001.016009606.x
3. Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation. https://doi.org/10.1037/t00742-000
Treatment of Depressive Disorders
Concurrent measures directed at the family and school, including psychotherapy
Pharmacotherapy (eg, selective serotonin reuptake inhibitors)
Transcranial magnetic stimulation (TMS) incorporated with other treatments
Hospitalization for inpatient management of acute depressive crises
Medications for Long-Term Treatment of Depression, Anxiety, and Related Disorders*
Medication | Uses | Half-life (hrs) | CYP substrates | Comments/Precautions |
|---|---|---|---|---|
SSRIs | ||||
CitalopramCitalopram | OCD in children ≥ 7 years | 35 hrs | 2C19, 2D6 | For 2C19 poor metabolizers, lower starting dose, slower titration and 50% reduction of maintenance dose |
Escitalopram (S-enantiomer of citalopram)Escitalopram (S-enantiomer of citalopram) | Major depression in children ≥ 12 years | 27–32 hrs | 2C19, 2D6 | — |
Fluoxetine†Fluoxetine† Norfluoxetine (active metabolite of fluoxetine)Norfluoxetine (active metabolite of fluoxetine) | OCD, GAD, separation anxiety, social anxiety, major depression in children > 8 years | 119–264 hrs Norfluoxetine: 144–384 hrs | 2D6 | — |
FluvoxamineFluvoxamine | GAD, separation anxiety, social anxiety, OCD in children > 8 years | 16 hrs | 2D6 | — |
Paroxetine†Paroxetine† | OCD in children > 6 years | 21 hrs | 2D6 | — |
SertralineSertraline | OCD, GAD, separation anxiety, social anxiety in children ≥ 6 years | 26 hrs | 2C19, 2B6, 2D6 | For 2B6 poor metabolizers, lower starting dose, slower titration and 25% reduction of maintenance dose |
SNRIs | ||||
DuloxetineDuloxetine | GAD in children 7–17 years | 10–12 hrs | 2D6, IA2 | SNRIs: have noradrenergic activity and can increase risk of hypertension |
Venlafaxine, immediate-releaseVenlafaxine, immediate-release | Depression in children ≥ 8 years | 5–11 hrs | 2D6 | SNRIs: limited data about optimal dose; concerns about increased suicidal behavior (in adolescents with pre-existing suicidal ideation); not as effective as other antidepressants, possibly because low doses have been used |
Venlafaxine, extended-releaseVenlafaxine, extended-release | GAD in children > 7 years | — | — | |
* The medications listed are used clinically for all the anxiety disorders, OCD, and depression. FDA approval has been obtained for some conditions; the lack of FDA approval for other conditions is due to a lack of sufficient studies and not due to other reasons. The most commonly used across all conditions are sertraline and escitalopram.* The medications listed are used clinically for all the anxiety disorders, OCD, and depression. FDA approval has been obtained for some conditions; the lack of FDA approval for other conditions is due to a lack of sufficient studies and not due to other reasons. The most commonly used across all conditions are sertraline and escitalopram. | ||||
† Fluoxetine and paroxetine are potent inhibitors of 2D6, decreasing the metabolism of antipsychotics (risperidone, aripiprazole, iloperidone, clozapine), increasing their plasma concentration. They can also inhibit the metabolism of some pain medications to their active metabolite (oxycodone to oxymorphone) but contrary to expectations, not codeine to morphine. Less potent inhibitors of 2D6 (sertraline) may have similar effects at the higher doses.† Fluoxetine and paroxetine are potent inhibitors of 2D6, decreasing the metabolism of antipsychotics (risperidone, aripiprazole, iloperidone, clozapine), increasing their plasma concentration. They can also inhibit the metabolism of some pain medications to their active metabolite (oxycodone to oxymorphone) but contrary to expectations, not codeine to morphine. Less potent inhibitors of 2D6 (sertraline) may have similar effects at the higher doses. Fluoxetine and paroxetine efficacy in treating depression is compromised when combined with trazodone (used to treat insomnia). This is attributed to 2D6 interactions and accumulation of methyl-chloro-piperazine a, trazodone metabolite associated with irritability and depression. Fluoxetine and paroxetine efficacy in treating depression is compromised when combined with trazodone (used to treat insomnia). This is attributed to 2D6 interactions and accumulation of methyl-chloro-piperazine a, trazodone metabolite associated with irritability and depression. Cannabis or cannabidiol (CBD) and tetrahydrocannabinol (THC) are moderate to strong inhibitors of CYP enzymes, increasing SSRI plasma concentrations and contributing to adverse effects (eg, diarrhea, dizziness, fatigue). Cannabis or cannabidiol (CBD) and tetrahydrocannabinol (THC) are moderate to strong inhibitors of CYP enzymes, increasing SSRI plasma concentrations and contributing to adverse effects (eg, diarrhea, dizziness, fatigue). | ||||
CYP = cytochrome P450; FDA = Food and Drug Administration; GAD = generalized anxiety disorder; OCD = obsessive compulsive disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = serotonin reuptake inhibitor.CYP = cytochrome P450; FDA = Food and Drug Administration; GAD = generalized anxiety disorder; OCD = obsessive compulsive disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = serotonin reuptake inhibitor. | ||||
Concurrent measures directed at the family and school must accompany direct treatment of the child to enhance continued functioning and provide appropriate educational accommodations. In a network meta-analysis of randomized trials including children and adolescents with depression, a combination of psychotherapy and antidepressants (eg, fluoxetine) outperformed psychotherapy (directed at the family and school must accompany direct treatment of the child to enhance continued functioning and provide appropriate educational accommodations. In a network meta-analysis of randomized trials including children and adolescents with depression, a combination of psychotherapy and antidepressants (eg, fluoxetine) outperformed psychotherapy (1). For preadolescents, the optimal approach is less clear. Most clinicians opt for psychotherapy in younger children; however, medications can be used in younger children (fluoxetine can be used in children ). For preadolescents, the optimal approach is less clear. Most clinicians opt for psychotherapy in younger children; however, medications can be used in younger children (fluoxetine can be used in children≥ 8 years), especially when depression is severe or has not previously responded to psychotherapy. Brief hospitalization may be necessary in patients with acute crises, especially when suicidal behavior is identified.
Selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacotherapy. The choice of specific agent depends on the age of the patient and pharmacokinetic properties of the drug. Fluoxetine and escitalopram are approved by the U.S. Food and Drug Administration (FDA) in children beyond ages 8 and 12, respectively, and are both first-line medications when an antidepressant is indicated (are the mainstay of pharmacotherapy. The choice of specific agent depends on the age of the patient and pharmacokinetic properties of the drug. Fluoxetine and escitalopram are approved by the U.S. Food and Drug Administration (FDA) in children beyond ages 8 and 12, respectively, and are both first-line medications when an antidepressant is indicated (2). Sertraline and paroxetine are other SSRIs that have been used off-label. Fluoxetine, and its active metabolite norfluoxetine, has a much longer half-life (7 to 15 days for the active metabolite) compared with other SSRIs like escitalopram and sertraline (33 and 26 hours, respectively) (). Sertraline and paroxetine are other SSRIs that have been used off-label. Fluoxetine, and its active metabolite norfluoxetine, has a much longer half-life (7 to 15 days for the active metabolite) compared with other SSRIs like escitalopram and sertraline (33 and 26 hours, respectively) (3). While the long half-life of fluoxetine promotes more consistent steady-state levels, it may have a delayed onset of action. In addition, if adverse effects manifest, they may take longer to resolve. Fluoxetine and paroxetine can also inhibit their own metabolism, leading to disproportionate increases in plasma levels at higher doses. By contrast, the shorter half-lives of escitalopram and sertraline may allow a more rapid dose titration and result in a quicker onset of action, and their lack of metabolic self-inhibition may be advantageous in aiding rapid clearance from the body. Children and their parents should be notified that it may take 6 to 8 weeks for these medications to achieve steady-state levels. (See table ). While the long half-life of fluoxetine promotes more consistent steady-state levels, it may have a delayed onset of action. In addition, if adverse effects manifest, they may take longer to resolve. Fluoxetine and paroxetine can also inhibit their own metabolism, leading to disproportionate increases in plasma levels at higher doses. By contrast, the shorter half-lives of escitalopram and sertraline may allow a more rapid dose titration and result in a quicker onset of action, and their lack of metabolic self-inhibition may be advantageous in aiding rapid clearance from the body. Children and their parents should be notified that it may take 6 to 8 weeks for these medications to achieve steady-state levels. (See tableMedications For Long-Term Treatment of Anxiety, Depression, and Related Disorders.)
SSRIs are substrates, inhibitors, and inducers of the P450 isozymes (3). See genetic testing panels for more information on identifying variants in drug-metabolizing enzymes (notably CYP2D6, CYP2C19, CYP2B6). These variants can increase the risk of SSRI adverse effects or reduced efficacy; testing is most useful before starting treatment or for patients who develop poor response or adverse effects, but not recommended for those doing well or without risk factors. (See table Medications For Long-Term Treatment of Anxiety, Depression, and Related Disorders). The clinical utility of these panels remains limited. Clinicians who order these tests should help families interpret the results (CPIC—Clinical Pharmacogenetics Implementation Consortium).
Behavioral adverse effects are idiosyncratic and may occur with any antidepressant and at any time during treatment. As a result, children and adolescents taking such drugs must be closely monitored. Treatment should generally be continued for 6 months, even when it appears that depressive symptoms have gone into remission (4). Most physicians choose to treat for 1 year or longer. If a decision is made to discontinue pharmacotherapy, SSRIs should be tapered gradually.
Other antidepressant medications that adult-based research has suggested act on both the serotonergic and adrenergic/dopaminergic systems may be modestly more effective; however, medications such as SNRIs (serotonin-norepinephrine reuptake inhibitors, eg, duloxetine, desvenlafaxine); mirtazapine; certain tricyclics, particularly clomipramine, also tend to have more adverse effects, such as hypertension. Such drugs may be especially useful in treatment-resistant cases. Nonserotonergic antidepressants such as bupropion and desipramine may also be used with a selective serotonin reuptake inhibitor (SSRI) to enhance efficacy. In very severe depression, psychotic and/or manic symptoms may require treatment with an additional that adult-based research has suggested act on both the serotonergic and adrenergic/dopaminergic systems may be modestly more effective; however, medications such as SNRIs (serotonin-norepinephrine reuptake inhibitors, eg, duloxetine, desvenlafaxine); mirtazapine; certain tricyclics, particularly clomipramine, also tend to have more adverse effects, such as hypertension. Such drugs may be especially useful in treatment-resistant cases. Nonserotonergic antidepressants such as bupropion and desipramine may also be used with a selective serotonin reuptake inhibitor (SSRI) to enhance efficacy. In very severe depression, psychotic and/or manic symptoms may require treatment with an additionalantipsychotic medication (5, 6). Duration of therapy and tapering schedule for SNRIs are similar to that of SSRIs (7).
Ongoing studies of investigational therapies vortioxetine and agomelatine demonstrate efficacy and safety in children and adolescents for treating depression. Ketamine and its more potent form, esketamine, shows promise in reducing depressive symptoms in adolescents (Ongoing studies of investigational therapies vortioxetine and agomelatine demonstrate efficacy and safety in children and adolescents for treating depression. Ketamine and its more potent form, esketamine, shows promise in reducing depressive symptoms in adolescents (8). However, the use of ketamine and esketamine is restricted and raises safety concerns.). However, the use of ketamine and esketamine is restricted and raises safety concerns.
Transcranial magnetic stimulation (TMS) is an noninvasive technique that applies brief magnetic pulses to the brain through an electromagnetic coil placed near the patient's scalp. TMS is thought to work by increasing glutamatergic and GABA activity, both of which are reported to be reduced in depression (9, 10). A TMS device has been used successfully in adolescents with depression (ages 15 and above) in conjunction with other treatments (eg, antidepressants, talk therapy), or when standard treatments have been ineffective. The use of TMS for younger children is under investigation. Preliminary data for adolescents and young adults with depression and anxiety also indicate significant improvement in those with depression and comorbid anxiety (11). Adverse effects reported in TMS include treatment site pain, headaches, transient blurry vision resolving after 5 days (12). The clinical effects and tolerability of TMS in adolescents are similar to those reported in adults (13-16). As in adults, relapse and recurrence of depression treated by TMS are common. Repetitive TMS can be helpful in treatment-resistant depression; however, studies in children and adolescents are limited (17).
Suicide risk and antidepressants
The risk of suicide associated with various antidepressant treatments has long been the topic of debate and research (18). In 2004, the U.S. Food and Drug Administration performed a meta-analysis including 23 trials of 9 different antidepressants that revealed a small but statistically significant increase in suicidal ideation in children and adolescents taking an antidepressant (paroxetine) compared with placebo (4% vs 2%) (). In 2004, the U.S. Food and Drug Administration performed a meta-analysis including 23 trials of 9 different antidepressants that revealed a small but statistically significant increase in suicidal ideation in children and adolescents taking an antidepressant (paroxetine) compared with placebo (4% vs 2%) (19). This discovery led to a boxed warning on all classes of antidepressants (eg, tricyclic antidepressants, SSRIs, SNRIs such as venlafaxine, and tetracyclic antidepressants such as mirtazapine).). This discovery led to a boxed warning on all classes of antidepressants (eg, tricyclic antidepressants, SSRIs, SNRIs such as venlafaxine, and tetracyclic antidepressants such as mirtazapine).
Subsequent observational and epidemiologic studies (20) have found no increase in the rate of suicide attempts or completed suicide in patients taking SSRIs. Also, despite a decrease in prescriptions for antidepressants following the boxed warning, the adolescent suicide rate increased by 14% (21). Using data from commercial claims (22) and nationwide registers (23) to estimate risks and benefits of medications in relation to suicidal events, SSRIs were associated with a significantly decreased number of suicidal events. For example, in a large, Swedish population-based cohort study that included children and adolescents, risk of suicidal behavior was highest in the month prior to initiating SSRIs; this risk reversed to a protective effect following the initiation of SSRIs (24). In a 2024 network meta-analysis evaluating SSRI use on suicide risk in patients with mental disorders, SSRIs were found to offer short-term protection against suicidal ideation (25). However, their long-term effectiveness in ameliorating suicidal ideation and behaviors is less clear.
Untreated depression is itself a risk factor for both suicidal ideation and completed suicide. The SSRIs are better tolerated than the SNRIs (26) and along with psychotherapy, could be considered as a first-line treatment. An increased rate of self-harm events (that did not include completed suicide) were reported in adolescents with moderate to severe depression who were treated with venlafaxine compared to those treated with an SSRI () and along with psychotherapy, could be considered as a first-line treatment. An increased rate of self-harm events (that did not include completed suicide) were reported in adolescents with moderate to severe depression who were treated with venlafaxine compared to those treated with an SSRI (27). Combining pharmacotherapy with psychotherapy and minimizing risk by closely monitoring treatment is recommended.
Whether or not medications are used, suicide is always a concern in a child or adolescent with depression; therefore:
Parents and mental health care practitioners should discuss the issues in depth.
The child or adolescent should be supervised at an appropriate level.
Psychotherapy with regularly scheduled appointments should be included in the treatment plan.
Pearls & Pitfalls
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Treatment references
1. Zhou X, Teng T, Zhang Y, et al. Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(7):581-601. doi:10.1016/S2215-0366(20)30137-1
2. Dwyer JB, Bloch MH. Antidepressants for pediatric patients. Curr Psychiatr. 8(9):26-42F, 2019.
3. Marken PA, Munro JS. Selecting a Selective Serotonin Reuptake Inhibitor: Clinically Important Distinguishing Features. Prim Care Companion J Clin Psychiatry. 2000;2(6):205-210. doi:10.4088/pcc.v02n0602
4. Miller L, Campo JV. Depression in Adolescents. N Engl J Med. 2021;385(5):445-449. doi:10.1056/NEJMra2033475
5. Kendall T, Morriss R, Mayo-Wilson E, et al. Assessment and management of bipolar disorder: Summary of updated NICE guidance. BMJ 349:g5673, 2014. doi: 10.1136/bmj.g5673
6. Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: Update 2013. Bipolar Disord. 15(1):1-44, 2013. doi: 10.1111/bdi.12025
7. Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry. 2019;6(6):538-546. doi:10.1016/S2215-0366(19)30032-X
8. Meshkat S, Rosenblat JD, Ho RC, et al. Ketamine use in pediatric depression: A systematic review. . Ketamine use in pediatric depression: A systematic review.Psychiatry Res. 2022;317:114911. doi:10.1016/j.psychres.2022.114911
9.Gonsalves MA, White TL, Barredo J, et al. Repetitive Transcranial Magnetic Stimulation-Associated Changes in Neocortical Metabolites in Major Depression: A Systematic Review. Neuroimage Clin 2022;35:103049. doi:10.1016/j.nicl.2022.103049
10.Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron. 2019;102(1):75-90. doi:10.1016/j.neuron.2019.03.013
11. Croarkin PE, Aaronson ST, Carpenter LL, et al. A Naturalistic Study of Transcranial Magnetic Stimulation Treatment in Adolescents and Young Adults With Depression and Anxiety. New Findings Ther. 2024;63(10), Supplement S306.
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Prognosis of Depressive Disorders
The recovery rate from depressive mood disorders in adolescents is >90%, but recurrence is common, with around two-thirds experiencing at least 1 recurrence (1, 2). Early-onset depression may be associated with a higher risk of persistent and recurrent depressive episodes into adulthood;higher levels of adult anxiety, substance use, social functioning; and worse health outcomes, including suicidal self-harm (3).
Prognosis references
1. Kiviruusu O, Strandholm T, Karlsson L, Marttunen M. Outcome of depressive mood disorder among adolescent outpatients in an eight-year follow-up. J Affect Disord. 2020;266:520-527. doi:10.1016/j.jad.2020.01.174
2. Copeland WE, Alaie I, Jonsson U, Shanahan L. Associations of Childhood and Adolescent Depression With Adult Psychiatric and Functional Outcomes. J Am Acad Child Adolesc Psychiatry. 2021;60(5):604-611. doi:10.1016/j.jaac.2020.07.895
3. Weavers B, Heron J, Thapar AK, et al. The antecedents and outcomes of persistent and remitting adolescent depressive symptom trajectories: a longitudinal, population-based English study. Lancet Psychiatry. 2021;8(12):1053-1061. doi:10.1016/S2215-0366(21)00281-9
Key Points
In children, depressive disorders may present as sadness or irritability.
Major depressive disorder involves feeling sad or irritable, or losing interest or pleasure in almost all activities for most of the day, nearly every day during a 2-week period..
Diagnosis of a depressive disorder is based on specific clinical criteria and appropriate laboratory tests are performed to exclude other disorders (eg, infectious mononucleosis, thyroid disorders, illicit drug use).
The family and school are involved while the child is being treated to enhance the child's continued functioning and provide appropriate educational accommodations.
For adolescents (as for adults), a combination of psychotherapy and antidepressants usually greatly outperforms either modality used alone; in younger children, most clinicians opt for psychotherapy although if needed, medications can be used (depending on the child's age).
In 2004, the FDA performed a meta-analysis that led to a boxed warning of an increased risk of suicidal ideation and suicidal behavior in children, adolescents, and young adults with all classes of antidepressants; however, subsequent analyses have shown a decrease in both suicidal ideation and behavior in the short term, but whether this effect is sustained is less clear.
Drugs Mentioned In This Article
