Karen Dineen Wagner, MD, PhD

To date, there are only 2 medications that have US Food and Drug Administration (FDA) approval for the acute treatment of major depressive disorder in children and adolescents: fluoxetine (ages 8 to 17 years) and escitalopram (ages 12 to 17 years). Placebo response rates in the 50% range have contributed to negative findings in double-blind placebo-controlled antidepressant trials for the treatment of 

 in youth. Further evidence-based antidepressant treatments are needed for children and adolescents with depression. Recent studies provide new information about treatment for depression in youth.

There have been 2 prior randomized double-blind placebo-controlled trials that evaluated the efficacy of duloxetine in the treatment of major depression in children and adolescents.

 Fluoxetine was the active control in these studies. Duloxetine was not statistically different from placebo on change from baseline to endpoint on the Children’s Depression Ratings Scale-Revised (CDRS-R) total score. Similarly, fluoxetine did not statistically differ from placebo. These studies were considered to be inconclusive since neither duloxetine nor fluoxetine separated from placebo on the primary outcome measure.

To further evaluate the efficacy and safety of duloxetine, Saito et al conducted a 6-week randomized double-blind placebo-controlled trial for treatment of children and adolescents with major depressive disorder in Japan.

 In this trial, 149 youth aged 9 to 17 years were randomized to duloxetine or placebo. All participants received 4 video sessions of 

Duloxetine final doses were either 40 or 60 mg/day. There was no significant difference on CDRS-R total score from baseline to endpoint between the duloxetine group and placebo group. Response rates (> 50% improvement on CDRS-R) were similar between duloxetine (32.4%) and placebo (32.4%) groups. The most common treatment-emergent adverse events for duloxetine were nausea, somnolence, decrease appetite, and nasopharyngitis.

The efficacy and safety of vortioxetine was assessed in adolescents (aged 12 to 17 years) with major depressive disorder.

 To minimize placebo response, this study used a 4-week single-blind lead-in period during which adolescents received a standard 3 session Brief Psychosocial Intervention (BPI) plus placebo. To reduce expectation bias, participants and their families were blinded to the time of the randomization. After the 4-week lead-in period, those patients who did not respond to treatment were randomized to 8 weeks of continued BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg (active control), or placebo.

In the lead-in, 784 patients were enrolled and 616 were randomized to 1 of the 4 treatments. The primary outcome measure was change in CDRS-R total score from randomization to week 8. The average effect of the 2 doses of vortioxetine was compared to placebo, and there was no significant difference between vortioxetine and placebo on the primary outcome measure. There was a statistically significant difference between fluoxetine and placebo on the primary endpoint. Response rates (≥ 50% change from randomization in CDRS-R total score) were 42% for vortioxetine 10 mg, 43% for vortioxetine 20 mg, 50% for fluoxetine, and 36% for the placebo groups. Importantly, the placebo response rate in this study was lower than the typical 50% range for other antidepressant trials in adolescents. This may be attributable to the single-blind lead-in and blinding for participants and families as to the timing of randomization employed in this study design. Of note, 13% (103 of 777 patients) of participants responded to treatment during the single-blind treatment phase. Treatment-emergent adverse events with an incidence of 5% or more for vortioxetine treatment were nausea, headache, vomiting, nasopharyngitis, diarrhea, and dizziness.

Antipsychotics are used to treat depression in children and adolescents who have not responded to prior treatment with an antidepressant. To date, there are no controlled trials of combination 

 and antidepressants to treat major depression in youth. Jeon et al examined whether there were neurological adverse events with the adjuvant use of antipsychotics with antidepressants in children and adolescents with depression.

 Their aim was to determine the risks of adjuvant use with antipsychotics compared to antidepressant only use in children with depression.

This retrospective cohort study used the Health Insurance Review and Assessment claims database criteria in Korea. Children and adolescents aged 2 to 18 years with depression who began treatment with antidepressants between 2010 and 2018 were included in the study population. The incidence of movement disorders (Parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tics) and seizures were assessed in 4 time-varying exposures with antidepressant-only use, antipsychotic-only use, concomitant use, and no use.

The final cohort included 9890 children and adolescents. The risk of movement disorders increased during the period of concomitant use (adjusted hazard ratio [aHR], 3.68) and antipsychotic-only use (aHR, 3.84) compared with antidepressant-only use. Similarly, the risk for seizures increased during the period of concomitant use (aHR, 2.06) and antipsychotic-only use (aHR, 2.05) compared to antidepressant-only use. For both cohorts, the antipsychotic dose in the concomitant use was lower than the dose in the antipsychotic-only use group. Higher dose of antipsychotics was associated with an increased risk of movement disorders (low dose: aHR, 3.28; high dose: aHR, 5.38). Similarly, increasing the daily dose of antipsychotics was associated with an increased risk of seizure development (low dose: aHR, 1.91; high dose: aHR, 2.30).

During the period of concomitant use of antipsychotic and antidepressants, the risk of movement disorder was highest with haloperidol, followed by polypharmacy, aripiprazole, risperidone, and quetiapine. Risk of seizure was highest with polypharmacy, followed by 

, aripiprazole, and risperidone. These results suggests that the potential development of movement disorders and seizure should be carefully considered with the use of adjunctive antipsychotics for the treatment of depression in children and adolescents.

Although not commercially available in the United States, agomelatine efficacy and safety were evaluated for the treatment of children and adolescents with major depressive disorder receiving psychosocial counseling in 9 countries.

 After a 3-week run-in period, 400 children and adolescents (aged 7 to 17 years) who were unresponsive to psychosocial therapy were randomized to agomelatine (10 mg/day or 25 mg/day), active control (fluoxetine 10 to 20 mg), or placebo for a 12-week trial. Standardized manualized psychosocial counseling was continued throughout the double-blind randomized controlled trial. At week 12, agomelatine 25 mg/day was statistically significant from placebo on the primary outcome measure of change in the CDRS-R a total score from baseline. Similarly, fluoxetine was significantly superior to placebo. Although statistically significant, Cohen’s effect size for agomelatine 25mg/day was small (0.29) and similar to fluoxetine (0.26).

The most frequent adverse events with agomelatine were thirst, dry mouth, and weight increase. Agomelatine has been associated with the potential to increase liver enzyme concentrations in the blood. The incidence of reversible aminotransferase increases more than 3 times the upper limit of normal was 1% in both agomelatine groups, 2% in fluoxetine group, and 0% in the placebo group in this trial.

In a case series, the effectiveness of a single esketamine administration either subcutaneous (SC) or intravenous (IV) on reducing depressive symptoms and 

 for adolescents with major depressive disorder and suicidal ideation was examined (Faria-Guimaraes et al 2022).

 Eight patients received 0.5 mg/kg esketamine SC, and 2 patients received 0.5 mg/kg esketamine IV.

A significant decrease in depressive symptoms (mean total Montgomery-Asberg Depression Rating Scale score) and suicidal ideation was found from baseline to 24-hour postadministration. The most frequently reported adverse events were dissociation (50%), dizziness (40%), and drowsiness (30%). There was no treatment-emergent suicidality. Although the results are promising, large-scale controlled trials are necessary to further assess the efficacy of esketamine for treatment of depression and suicidality in adolescents with major depression.

In addition to antidepressant medication, 

 (ECT) is an option for treatment resistant depression. To date, there are no controlled trials of ECT for the treatment of children and adolescents with major depression. A recent systematic review examined the effectiveness and adverse-event profile of ECT for treatment-resistant mood disorders in children and adolescents.

 The review included 41 studies (20 case series, 2 case-controlled studies, and 19 case reports). Out of 601 patients, 322 were diagnosed with unipolar depressive disorder. Patients received an average of 12 ECT treatments.

Most studies used the Clinical Global Impression Scale as a measure of improvement and reported response rates for depression ranging from 53% to 77%. For those studies that used objective depression symptom ratings scales, treatment improvement averaged 64%. For those studies with n > 30, response rates for depression were 70 to 82%. The Mini-Mental State Exam was used in 7 studies, and there was no evidence of significant posttreatment cognitive impairment. However, subjective reports of cognitive symptoms were common, particularly short-term memory complaints. Other common adverse effects reported were headache, nausea, vomiting, confusion, agitation, and muscle soreness. Treatment-emergent mania and prolonged seizures were reported in some cases. Discontinuation due to adverse effects occurred in 1.5% of cases.

Based on this review, the investigators suggest that ECT is safe and effective for the treatment of mood disorders in child and adolescent populations and should be considered in severe and treatment-refractory cases. The investigators acknowledge the limitation of the data since most of the literature was case series. Further investigation of the efficacy of ECT for treatment-resistant mood disorders in children and adolescents is needed.

is professor and chair of the Department of Psychiatry and Behavioral Sciences at the University of Texas Medical Branch in Galveston, Texas.

1. Atkinson SD, Prakash A, Zhang Q, et al. 

A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder.

2. Emslie GJ, Prakash A, Zhang Q, et al. 

A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder.

3. Saito T, Ishida M, Nishiyori A, et al. 

Efficacy and safety of duloxetine in children and adolescents with major depressive disorder in Japan: a randomized double-blind placebo-controlled clinical trial followed by an open-label long-term extension trial.

4. Findling RL, DelBello MP, Zuddas A, et al. 

Vortioxetine for major depressive disorder in adolescents: 12- week randomized, placebo-controlled, fluoxetine-referenced, fixed-dose study.

 Association of treatment with antipsychotics, antidepressants, or both with movement disorders and seizures among children and adolescents with depression in Korea.

5. Faria-Guimarães D, Vieira F, Souza-Marques B, et al. 

Letter to the editor: antidepressant and antisuicidal effects of esketamine in adolescents with major depressive disorder and suicidal ideation: a case series.

6. Arango C, Buitelaar JK, Fegert JM, et al. 

Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomized, controlled, phase 3 trial in nine countries.

7. Faria-Guimarães D, Vieira F, Souza-Marques B, et al. 

8. Castaneda-Ramirez S, Becker TD, Bruges-Boude A, et al. 

Systematic review: electroconvulsive therapy for treatment-resistant mood disorders in children and adolescents.

Articles

Further evidence-based antidepressant treatments are needed for children and adolescents with depression.

Update on Depression Treatments for Youth

SPECIAL REPORT: CHILD & ADOLESCENT PSYCHIATRY 

Child and adolescent psychiatry has always been important, and maybe it is even more so since the pandemic. As noted in an earlier 

, COVID-19 has brought a complex array of factors (ie, uncertainty, social isolation, and parental angst) that have impacted youth mental health. We know predictability is a stabilizing force for children and adolescents, and that has been disrupted since the start of the pandemic. We likely will see an increased need for mental health care in the postpandemic period. This article summarizing new research and this Special Report will help support efforts in providing optimal care to our patients.

Several recent studies provide clinically relevant information about depression in children and adolescents on a range of topics including family history, long-term outcomes, ketamine treatment, and COVID-19’s impact on depression and suicide risk.

It is well known that a family history of depression increases risk of depression for offspring. A recent retrospective study examined the association of multigenerational family history of depression and lifetime depressive disorders in children.

(ABCD), which included psychiatric assessments of 11,200 children (mean age 9.9 years). Participants’ parents provided information about depression history in second-degree and first-degree relatives (ie, grandparent’s generation and parent’s generation).

These findings reaffirm the importance of obtaining a family history when assessing children.

Risk of depressive disorders increased with a multigenerational family history of depression. The weighted prevalence of depressive disorder and suicidal behavior were 3.8% and 5.0%, respectively, when neither parent/grandparent generation had depression; 5.5% and 7.2% when grandparent generation had depression; 10.4% and 12.1% when parent generation had depression, and 13.3% and 15.0% when both parent/grandparent generations had depression. These findings reaffirm the importance of obtaining a family history when assessing children.

Another recent study added to the expanding literature about the adverse consequences of depression in youth. In this study, the long-term outcomes of childhood/adolescent depression were examined using data from the Great Smokey Mountains Study, a longitudinal representative study of children in 11 rural counties of North Carolina.

 The analysis included 1420 participants from 3 cohorts of children aged 9, 11, and 13 years. Annual assessments were conducted until age 16; assessments were then conducted at ages 19, 21, 25, and 30 years.

Child and Adolescent Psychiatric Assessment

 was used to obtain information regarding childhood depression status, other psychiatric disorders, service use, and adversities/hardships, which included low socioeconomic status, unstable family structure, family dysfunction, family maltreatment, and peer victimization. Adult psychiatric disorders were assessed using the Young Adult Psychiatric Assessment. Adult functioning including health, risky/illegal behaviors, wealth (financial/educational), and social function were also assessed.

By age 16, 7.7% of the participants met full criteria for a depressive disorder (ie, major depression, dysthymia, or depression NOS). Childhood/adolescent depression was associated with other psychiatric disorders such as anxiety disorders, attention-deficit/hyperactivity disorder, oppositional defiant conduct disorder, substance use disorder, as well as adversities/hardships. Researchers found child/adolescent depression was associated with higher rates of adult anxiety, depression and substance use disorders, as well as worse functional outcomes (ie, general health, risky/criminal behavior, financial/educational status, and poor social functioning). No sex-specific associations between childhood/adolescent depression and adult outcomes were found. Adolescent-onset depression was associated with more adverse adult outcomes than childhood-onset depression. Importantly, youth with childhood/adolescent depression who received specialty mental health services had a lower risk for any adult psychiatric disorder, but there was negligible effect on functional outcomes.

There are very limited data available in the adolescent population on ketamine. Dwyer et al

 conducted the first controlled trial of intravenous ketamine for adolescent treatment-resistant depression. Participants (n=17) were aged 13 to 17 years and had treatment-resistant depression, which was defined as failure to respond to at least 1 prior 8-week trial of antidepressants at therapeutic doses. The average number of failed prior antidepressants was 3.2. Depression was fairly chronic in these adolescents, with an average duration of 21 months for the current episode.

Depressive symptoms were significantly reduced 24 hours after a single ketamine infusion compared with midazolam.

In the randomized, double-blind, single- dose crossover trial, adolescents received a single intravenous infusion of either ketamine (0.5 milligrams per kilogram over 40 minutes) or midazolam (0.045 milligrams per kilogram over 40 minutes) and the alternate compound 2 weeks later. Adolescents remained on their current medication during the trial; the majority were on antidepressant medication. The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS) 24 hours following treatment.

Depressive symptoms were significantly reduced 24 hours after a single ketamine infusion compared with midazolam. Clinical response (defined as more than a 50% reduction in MADRS score within 3 days following treatment) was significantly higher for ketamine than midazolam: 76% and 35%, respectively. MADRS ratings after ketamine were significantly lower at each post-baseline time point up to day 14 as compared with midazolam. Significant dissociative symptoms were found with ketamine, and were time limited, with an elevation at the 1-hour time point and return to baseline by the 2-hour time point. Based on these findings, large scale controlled trials of ketamine for adolescent treatment resistant depression are warranted.

To address the concern of COVID-19’s impact on youth, a recent study examined changes in depression and suicide risk screening, as well as percentage of positive screens during the COVID-19 pandemic.

 Electronic health record data were obtained from a large pediatric primary care network from Children’s Hospital of Philadelphia, which included 29 urban, suburban, and semirural practices. Screening for depression and suicide risk during primary care visits for adolescents aged 12 to 21 years was compared for the periods of June to December 2019 (prepandemic n=45,504) and June to December 2020 (pandemic n=47,684). The Patient Health Questionnaire – Modified for Teens (PHQ-9-M) was used to screen for depression symptoms and suicide risk.

Depression screening rates during well visits declined from 77.6% to 75.8% during the pandemic period but gradually increased to prepandemic levels. There was an increase in the percentage of adolescents screening positive for moderate-to-severe depression—from 5.0% in prepandemic period to 6.2% in the pandemic period—particularly for female, non-Hispanic Black, and non-Hispanic White adolescents. Similarly, there was an increase in positive suicide risk screens from 6.1% to 7.1%, which was greater among female than male adolescents.

These findings demonstrates the importance of routine screening for depression and suicide in adolescents, especially during this pandemic period.

New research is critical to informing and optimizing care. The information in this Special Report will further enable you to address the mental health needs of children and adolescents.

 is professor and chair, Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, Texas. She is immediate past president of the American Academy of Child and Adolescent Psychiatry and a member of the 

1. van Dijk MT, Murphy E, Posner JE, et al. 

Association of multigenerational family history of depression with lifetime depressive and other psychiatric disorders in children: results from the Adolescent Brain Cognitive Development (ABCD) Study

2. Vaughn-Coaxum RA, Merranko J, Birmaher B, et al. 

Longitudinal course of depressive symptom severity among youths with bipolar disorders: Moderating influences of sustained attention and history of child maltreatment

3. Dwyer JB, Landeros-Weisenberger A, Johnson JA, et al. 

Efficacy of intravenous ketamine in adolescent treatment-resistant depression: a randomized midazolam-controlled trial

COVID-19 and adolescent depression and suicide risk screening outcomes

What's new and noteworthy in children and adolescent psychiatry?

Supporting Youth: New Findings in Youth Depression and Beyond

COVID-19 has brought about a complex array of factors (

) that have an impact on the mental health of children and adolescents. Predictability is a stabilizing force for children and adolescents, but it has been disrupted since the COVID-19 outbreak.

Children have many worries related to the consequences of COVID-19 such as whether they will see their friends and relatives, go to school or get sick. It is often difficult for parents to calm their children’s anxieties because of the uncertainty in their lives. Parents are typically adept at making plans for their children, but future plans are currently on hold. The challenges facing parents may interfere with their usual ability to address their children’s emotional needs.

survey was administered to 359 children and 3254 adolescents aged 7 to18 years during the spread of COVID-19 in China.

 The questionnaire included a depression scale, an anxiety scale, and a coping style scale. It showed 22.3% of youth had scores indicative of clinical depressive symptoms, which is higher than the 13.2% estimated prevalence of youth depression in China. Anxiety symptom levels were also higher after COVID-19 than previously reported. Youth who had a family member or friend with COVID-19 had higher levels of anxiety than those who did not. A problem-focused coping style was associated with lower levels of clinical depressive symptoms, whereas an emotion-focused coping style was associated with higher levels of clinical depressive symptoms.

, 8079 junior and senior high school students in China completed assessments about depressive and anxiety symptoms during the COVID-19 epidemic period. Using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD -7) questionnaire.

 The prevalence of depressive symptoms was 43.7%, anxiety symptoms 37.4%, and both depressive and anxiety 31.3%. Depressive and anxiety symptoms were higher in females, and with increasing grade level from junior to senior high. Students without depressive and anxiety symptoms had more knowledge about preventive and control measures, as compared to those students with depressive and anxiety symptoms.

Mental health of children was assessed during the lockdown in Bangladesh via an online 

of 384 parents with children aged 5 to15 years.

 Children’s depression, anxiety, and sleep disorder scores were grouped into severity categories. Severity and percentages of mental health problems in the children were as follows: subthreshold (43%), mild (30.5%), moderate (19.3%), and severe (7.2%).

The emotional impact of the COVID-19 quarantine was 

for children and adolescents from Italy and Spain.

 Participants included 1143 parents of children aged 3 to 18 years who completed a survey about the effects of the quarantine on their children, compared to before the home confinement period. The study found 85.7% of parents reported changes in their children’s emotions and behaviors during the quarantine. The most frequently observed changes were difficulty concentrating (76.6%), boredom (52%), irritability (39%), restlessness (38.8%), nervousness (38%), loneliness (31.3%), uneasiness (30.4%), and worries (30.1%). About 75% of parents reported feeling stressed about the quarantine situation. Parental stress was associated with increased reports of emotional and behavioral symptoms in their children.

 examined the impact of social isolation and loneliness on mental health in children and adolescents.

 The relationship between loneliness and mental health problems in healthy children and adolescents was assessed to determine if quarantine and social isolation are predictive of future mental health problems. The review included 63 studies with a total of 51,576 participants. Social isolation and loneliness increased the risk of depression up to 9 years later. Duration rather than intensity of loneliness was more strongly associated with mental health symptoms. The findings from this literature review on loneliness and social isolation have potential implications for the current COVID-19 pandemic. These researchers suggest that 

for youth during the disease containment measures for COVID-19 may affect the future mental health of youth. They recommend preventive support and early intervention to address the mental health needs of children and adolescents during the COVID-19 pandemic.

Overall, the research demonstrates that COVID-19 is affecting the mental health of children and adolescents and that depression and anxiety are prevalent. Additional research is needed, however, to assess the short- and long-term effects of COVID-19 on children’s overall mental health.

So, what can clinicians do for their patients? For clinicians who treat children and adolescents, talk with them about the impact of 

on their lives and assess its potential relationship to their current mental health. For some youths, the psychosocial impact of COVID-19 may be related to the onset or exacerbation of their current mental health problems. For other youths, particularly those with social anxiety disorders, remaining at home and doing online schooling may temporarily relieve their anxiety, but this is not a long-term solution and may result in overwhelming anxiety when it is necessary to return to school.

For clinicians who treat parents of children and adolescents, it is important to inquire about the mental health of their children during this pandemic. Parents’ mental health may be affected by their children’s mental health. Encourage parents to seek an evaluation for their children if they have any concerns about their children’s mental health. Early intervention may prevent long term mental health consequences from this COVID-19 pandemic.

 is professor and chair, Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, TX. She is immediate past president of the American Academy of Child and Adolescent Psychiatry.

An investigation of mental health status of children and adolescents in china during the outbreak of COVID-19

Prevalence and socio-demographic correlates of psychological health problems in Chinese adolescents during the outbreak of COVID-19

3. Yeasmin S, Banik R, Hossain S, et al. 

Impact of COVID-19 pandemic on the mental health of children in Bangladesh: A cross-sectional study

4. Orgilés M, Morales A, Delvecchio E, et al. 

Immediate psychological effects of the COVID-19 quarantine in youth from Italy and Spain

. Accessed September 22, 2020. https://psyarxiv.com/5bpfz/

5. Loades ME, Chatburn E, Higson-Sweeney N, et al. 

Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19

 [published online ahead of print, 2020 Jun 3]. 

Studies around the world are measuring the effects of the pandemic on children and adolescents.  

New Findings About Children’s Mental Health During COVID-19

The prevalence of depression has been increasing in youths. Depression in this age group is associated with impairments in peer relationships, family life, and academic performance. Of significant concern is the increased risk of 

 is essential to prevent the devastating sequelae of untreated depression in youth. Parents as well as teenagers should be educated about the symptoms of depression, its course, and treatments for this condition. Clinicians would benefit from educational materials to give to parents of depressed children, as well as updates about depression in youth.

American Academy of Child and Adolescent Psychiatry

 (AACAP), I focused on depression awareness and screening for my presidential initiative. Components of this initiative included education about depression in youths, expansion of the AACAP Depression Resource Center, and collaboration with professional organizations.

 With the participation of a stellar Task Force, the goals of the initiative have been achieved.

A number of resources have been produced as part of this initiative that are useful for clinicians who treat children and adolescents with depression, for parents, and for teenagers. The 

 contains up-to-date information about depression in children and adolescents. Importantly, there are resource sections specifically for clinicians, parents, and youth. The Depression Resource Center contains frequently asked questions about depression such as causes, signs and symptoms, course and treatments. Screening and rating scales for depression, books and Apps related to depression, and treatment resources and videos of clinician experts discussing depression as well as a video on depression for teenagers are included in the Resource Center.

Facts for Families on Depression in Children and Teens

 provides information for parents and youth about the symptoms of depression. It can be printed in a handout form for parents and teenagers.

The Parents’ Medication Guide on Depression

, a joint publication between AACAP and the 

, has been updated to provide information about medication treatment for depression in this age group. This medication guide is helpful for parents when clinicians plan to initiate medication treatment for depressed children.

Policy Statement on Depression Screening in Youth

. AACAP recommends routine screening for depression in children/adolescents ages 8 and older across health care settings, including primary care as well as mental health care settings.

 was published in Child and Adolescent Psychiatric Clinics of North America.

 The issue includes chapters on child and adolescent depression across settings (child welfare system, juvenile justice system, primary care setting, military setting, schools, colleges and home), comorbid clinical conditions (

, hearing impairment, medical conditions, HIV/AIDS, and substance use disorders), and ethnic and cultural identities (African American, Latino, American Indian, and 

). The aim of this edition is to assist clinicians who treat youths with depression to better understand unique aspects of assessment, course, and treatment of youths in these diverse populations.

 is an online CME course that was launched as part of the initiative. The course on depression uses video and lectures from past ACCAP activities on depression.

Journal of the American Academy of Child and Adolescent Psychiatry

 focused on depression and depression screening as part of this initiative. Some of the publications included a master clinician review on parental depression and family health and wellness

; a 13-year follow-up on psychotherapy effects on youth depression

; and mechanisms of change in a school-based depression prevention trial at the transition to high school.

Although the initiative is complete, the Depression Resource Center will continue to be updated to provide timely information for clinicians, parents, and youth.

 is Professor and Chair, Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, TX. She is Immediate Past President of the American Academy of Child and Adolescent Psychiatry, and she is on the Editorial Board of 

1. Wagner KD. Presidential address: Depression Awareness and Screening in Children and Adolescents. 

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	2. Ng WY, Wagner KD. Depression in special populations. 

Child and Adolescent Psychiatric Clinics of North America. Clinics Reviews Articles.

 New York: Elsevier; 2019.
	3. Beardslee WR. Master clinician review: Parental depression and family health and wellness: what clinicians can do and reflections on opportunities for the future. 

. 2019;58:759-767.
	4. Eckshtain D, Kuppens S, Ugueto A, et al. Meta-analysis: 13-year follow-up of psychotherapy effects on youth depression. 

. 2020;59:45-63.
	5. Blossom JB, Adrian MC, Vander Stoep A, McCauley E. Mechanisms of change in the prevention of depression: an indicated school-based prevention trial at the transition to high school. 

Depression in children and adolescents is associated with several impairments but the most significant concern is the increased risk of suicide in youths with depression.

Depression Awareness and Screening in Children and Adolescents

Cannabis is a widely used drug of abuse in adolescents. With legalization of marijuana, adolescent cannabis use may increase substantially. Clinicians are often faced with a depressed, anxious, or suicidal adolescent who uses cannabis to self-medicate symptoms and is unwilling to stop using cannabis. Several recent studies provide further evidence of the adverse mental health consequences of cannabis use in adolescents.

A systematic review and meta-analysis examined the risk of adolescent cannabis use in the development of major depression, anxiety, and suicidal behavior.

 The analysis included longitudinal and prospective studies of cannabis use in adolescents aged younger than 18 years who were then assessed in young adulthood (aged 18-32 years). Eleven studies for a total sample of 23,317 adolescent cannabis users were included in the analysis.

The risk of depression (odds ratio [OR] = 1.4), suicidal ideation (OR = 1.5), and suicide attempt (OR = 3.5) in young adulthood was significantly higher in adolescent cannabis users than in nonusers; a significantly increased risk was not found for the development of anxiety disorders (odds ratio = 1.2). It is important to note that the increased risk of depression and suicidal behavior in young adulthood was present even in the absence of a premorbid psychiatric condition. Based on this study, the researchers concluded that the estimated population attributable risk of depression from cannabis use is 7.2% in adolescents; approximately 413,326 cases of adolescent depression are potentially attributable to cannabis use.

Age, cannabis use frequency, and mental health problems

The effects of age on cannabis use frequency and cannabis use disorder on psychotic, depression, and anxiety symptoms in adolescents and adults were evaluated by Leadbeater and colleagues.

 A randomly recruited sample of 662 adolescents aged 12 to 18 years was assessed over a 10-year period.

More frequent cannabis use was significantly associated with more depressive symptoms from ages 16 to 19 and after age 25. Furthermore, cannabis use was significantly associated with psychotic symptoms after age 22. There was no association between frequency of cannabis use and anxiety symptoms in the study sample. With regard to cannabis use disorder, there was an association with higher depressive symptoms at ages 19 to 20 and after age 25; psychotic symptoms after age 23 were associated with adolescent cannabis use disorder. Cannabis use disorder was also associated with higher anxiety symptoms at ages 26 to 27.

 examined the relationship between cannabis use and cognitive development in adolescents. The study sample included 3826 seventh graders (mean age, 12.7 years) from 31 schools in the Montreal area. These youth were assessed annually for 4 years (grades 7-10) on cannabis use, alcohol use, and cognitive functioning, including recall memory, perceptual reasoning, inhibition, and working memory. The assessments were completed via a confidential annual web-based survey during class time to assess cognition and substance use.

Adolescent cannabis and alcohol use were associated with lower working memory, perceptual reasoning, and inhibitory control. Of particular concern, cannabis use showed neuroplastic (concurrent effect) and neurotoxic (lasting effect) of cannabis, which was not found for alcohol use. For example, when adolescent cannabis use increased in frequency in a given year, there was a reduction in delayed recall memory and perceptual reasoning in that same year.

Cannabis use in a given year was also associated with impaired inhibitory control and working memory a year later. These findings are particularly worrisome given that cannabis use in this sample was low and infrequent, yet cognitive changes were detected with small increases in cannabis use.

Decreased threat responsiveness as a function of cannabis use disorder has been reported in adolescents.

 Eighty-seven adolescents with cannabis use disorder and/or alcohol use disorder were scanned with fMRI during a looming threat task. During this task, adolescents were shown images of threatening or neutral human faces or animals that appeared to be looming (increasing size over time) or receding (decreasing size over time).

Adolescents with higher severity of cannabis use disorder symptoms showed decreased response to looming stimuli within the rostral frontal and fusiform gyrus and amygdala. There were no associations with alcohol use disorder symptoms. The researchers speculate that decreased threat responsiveness may be a neurotoxic effect of cannabis abuse and related to conduct problems (less concern about negative consequences) associated with cannabis use disorder.

Mental health effects and increasing cannabis potency

The potency of cannabis with rising concentration of delta(9)tetrahydrocannabinol (THC) has been increasing over the past few decades. Wilson and colleagues

 reviewed the effects of increasing cannabis potency on adolescent health.

High-potency cannabis was associated with five times higher probability of having a diagnosis of a psychotic disorder compared with cannabis nonusers. Increased risk of relapse following first episode of psychosis was associated with frequent use of high-potency cannabis. In cross-sectional studies, high-potency cannabis use was associated with depression and anxiety in adolescent cannabis users. These findings are concerning because adolescents typically have little information about the potency of cannabis that they are using.

These recent studies add significantly to the evidence that cannabis use in adolescents has adverse effects on mental health with risk for depression, psychosis, and cognitive impairment, especially inhibitory control. Adolescents and their parents need to be informed about the adverse consequences of cannabis use, whether the adolescent is or isn’t currently using substances. Many psychiatric disorders increase the risk for cannabis use and conversely frequent cannabis use, especially higher potency cannabis, increases the likelihood of psychiatric disorders. With pending legalization of marijuana and increased access for adolescents, the public needs to be informed about the deleterious mental health effects of cannabis use in adolescents.

Dr Wagner is Professor and Chair, Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, TX. She is President of the American Academy of Child and Adolescent Psychiatry.

Gobbi G, Atkin T, Zytynski T, et al. Associations of cannabis use in adolescence and risk of depression, anxiety, and suicidality in young adulthood: a systematic review and meta-analysis. 

Leadbeater BJ, Ames ME, Linden-Carnichael AN. Age-varying effects of cannabis use frequency and disorder on symptoms of psychosis, depression and anxiety in adolescents and adults. 

Morin JG, Afzali MH, Bourque J, et al. A population-based analysis of the relationship between substance use and adolescent cognitive development. 

 Blair RJ, White SF, Tyler PM, et al. Threat responsiveness as a function of cannabis and alcohol use disorder severity. 

 Wilson J, Freeman TP, Mackie CJ. Effects of increasing cannabis potency on adolescent health. 

Cannabis is a widely used drug of abuse in adolescents. With legalization of marijuana, adolescent cannabis use may increase substantially.

More Reasons for Concern About Adolescent Cannabis Use

Anxiety disorders are the most common psychiatric condition in youth. Lifetime prevalence rates for any anxiety disorder in adolescents is 31.9%.

Anxiety disorders occur early in childhood with a median age of onset of 6 years. These disorders lead to significant impairment in academic, social, and family functioning. In clinical practice, it is common to see children who are homeschooled because of severe untreated anxiety disorders. Untreated anxiety disorders may also be a precursor for MDD. There have been some recent studies and meta-analyses that address mental health hospitalization, optimal treatment, and long-term outcome for children and adolescents with anxiety disorders.

 examined the incidence of mental health-related hospitalization, treatment for self-harm, and emergency room visits in children and adolescents who had a new diagnosis of an anxiety disorder. The sample included 198,450 youths aged 3 to 17 years who were included in the MarketScan claims database that contains health plan data for those covered by employer-sponsored private health insurance across the US. Youths were followed for up to 2 years after diagnosis of an anxiety disorder, and youths without anxiety diagnoses were included as comparators.

The median age of the youths with anxiety disorders was 12 years old and 55% were female. The incidence of new anxiety diagnoses were as follows: unspecified anxiety disorder (53%), generalized anxiety disorder (25%), obsessive-compulsive disorder (5%), and posttraumatic stress disorder (4%). Within a one-year period from diagnosis, 2% of these youths had a mental-health related hospitalization, 1% had a recorded suicidal ideation claim, and .08% had inpatient treated self-harm. Emergency room visits were high (20%), and 1.4% had an anxiety-related emergency room visit within one year of a new anxiety disorder diagnosis. The two-year incidence of these events was similar.

Rates of these events were highest in older children with baseline comorbid depression. Rates were lower in the comparator group (mental health-related hospitalization 0.5%, treated self-harm 0.01%, and emergency room visits 13%). Findings from this study further demonstrate the significant adverse effects of anxiety disorders in children and adolescents.

 examined the magnitude of antidepressant response and the effect of antidepressant class and dose on improvement in pediatric anxiety disorders. The anxiety disorders included generalized anxiety disorder, social anxiety disorder, and separation anxiety disorder. Data were obtained from 9 trials of antidepressant medications, which included 5 SSRIs and 4 SNRIs for 1673 youths with anxiety disorders who were randomly assigned to an antidepressant or placebo. The median duration of the treatment was 10 weeks. The SSRIs included fluoxetine, fluvoxamine, paroxetine, and sertraline. SNRIs included atomoxetine, venlafaxine, and duloxetine.

By week 2 there were statistically significant differences between medication and placebo, and by week 6 there were clinically significant treatment differences between antidepressant medication and placebo. There were also class differences in effectiveness between SSRIs and SNRIs. Compared with SNRIs, SSRIs showed significantly greater improvement by the second week of treatment, which was maintained through week 12.

There was no difference in response over time between high- and low-dose SSRI treatment; however high dose resulted in statistically significant improvement earlier (week 2) compared with low dose. The results of 

 demonstrate that response occurs early with antidepressant treatment of pediatric anxiety disorders and that SSRIs have earlier and greater efficacy than SNRIs for the treatment of children and adolescents with generalized anxiety disorder, social anxiety disorder, and separation anxiety disorder.

 was undertaken to compare different types of psychotherapies for the treatment of children and adolescents with anxiety disorders.

 The study comprised 101 randomized clinical trials with a total of 6625 patients in the analyses. There were 11 different psychotherapies including:

• Individual BT with parental involvement

• Group cognitive behavioral therapy (CBT)

• Individual CBT with parental involvement

The 4 control conditions included wait list, psychological placebo, no treatment, and treatment as usual.

All of the psychotherapies were found to be more effective than the wait list control. Of all of the therapies, only group CBT was significantly more effective in treating anxiety symptoms than the other psychotherapies or the control conditions at both posttreatment and at short-term follow up (the median duration of acute treatment was 12 weeks and the longest follow up was 6 months). Based on these findings, the researchers suggest that group CBT may be the initial treatment for youth with anxiety disorders; however these findings require further research.

Child/Adolescent Anxiety Multimodal Extended Long-Term Study

 provides information about long-term outcome for youths who received acute (12 week) treatment for pediatric anxiety disorders.

 The study included 319 children and adolescents with separation anxiety disorder, social anxiety disorder, and/or generalized anxiety disorder. Study participants were randomized to either 12 weeks of sertraline, CBT, sertraline plus CBT, or placebo. They were assessed annually over 4 years.

Across all 4 years, 21.7% of youth were in stable remission, 30% were chronically ill, and 48% relapsed. Those youths who responded to acute treatment were more likely to be in remission during the course of the follow-up. There was no association between the initial treatment group and remission status. These findings indicate that anxiety disorders in children and adolescents are often chronic and may require longer-term or intermittent treatment beyond acute treatment.

 Merikangas KR, He JP, Burstein M, et al. 

Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A)

 Bushnell GA, Gaynes BN, Compton, SN, et al. 

Incidence of mental health hospitalizations, treated self-harm, and emergency room visits following new anxiety disorder diagnoses in privately insured US children

. October 24, 2018; E-pub ahead of print.

Recent studies and meta-analyses discussed here address mental health hospitalization, optimal treatment, and long-term outcome for children and adolescents with anxiety disorders.