BHIPP Bulletin

Volume 9, Issue 4

October 2023

Pharmacological Treatment of

Depression in Youth

This month's BHIPP Bulletin is a contribution from

Rheanna Platt, MD, Assistant Professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins School of Medicine and BHIPP Consultant.

More than half of youth with mild to moderate depression respond well to evidence-based psychotherapy or behavioral interventions such as Cognitive Behavioral Therapy (CBT) or Interpersonal Therapy (IPT) (Zuckerbrot et al., 2018; Cheung et al., 2018). However, these treatments may not always be available or accessible, and in some cases, medication is preferred. Medication may also be indicated based on the severity of symptoms, the presence of comorbidities such as anxiety or OCD, or if symptoms have not significantly improved with psychotherapy. 

In this issue, we will review guidelines and recommendations for the pharmacologic treatment of depression in children and adolescents in primary care. Many of the principles below are reflected in the Guidelines for Adolescent Depression Treatment in Primary Care (GLAD-PC) Part I and Part II, which were developed and revised with expert consensus and include recommendations for screening and management of depression in pediatric primary care (Zuckerbrot et al., 2018; Cheung et al., 2018).

General Principles of Depression Pharmacotherapy

  • When starting medication for depression, it is important for PCPs to set treatment expectations with patients and families. As most antidepressants require gradual titration (starting at a low dose and increasing gradually every 2-3 weeks) and can take 6–8 weeks at therapeutic dose to reach maximum effect, it is important for patients and families to be aware that the lack of an immediate response or change does not necessarily indicate a lack of efficacy. Unless there are significant side effects, medication should be continued for at least 4–6 weeks to determine efficacy. 
  • Similarly, it is recommended that medication be continued for at least 6 months after remission of symptoms to decrease the likelihood of relapse. 
  • In most cases, it is recommended that stopping medication occurs gradually in order to minimize discontinuation symptoms, including but not limited to dizziness, drowsiness, nausea, lethargy, and headache. An exception would be if there were severe side effects. 
  • Combination treatment –medication and psychotherapy—is generally more effective than either modality alone. 

Specifics about Depression Pharmacotherapy

Selective Serotonin Reuptake Inhibitors (SSRIs) are first-line pharmacotherapy for pediatric depression. Two SSRIs are FDA-approved for the treatment of depression in pediatric patients: Fluoxetine (Prozac) is approved for depression in children ages 8 and above, and Escitalopram (Lexapro) is approved for depression in adolescents aged 12 and above. Other SSRIs, such as Sertraline (Zoloft), are also commonly used off-label for pediatric depression. 

The GLAD-PC guidelines suggest Fluoxetine as the first-line recommendation among SSRIs due to several factors, including FDA approval (and age of approval) and half-life (Fluoxetine’s long half-life can decrease the effects of missed doses). Due to Fluoxetine’s FDA approval, multiple successful medication trials, and long half-life, Fluoxetine is recommended as the first choice in the absence of other considerations or contraindications. However, it is important to note that Fluoxetine is a strong inhibitor of CYP450 2D6 and therefore has the potential for drug-drug interactions. When drug-drug interactions are a consideration, Escitalopram is a good choice due to its minimal effects on CYP enzymes. 

While not FDA approved for depression, several other SSRIs are frequently used off-label, particularly in cases with comorbid anxiety disorders. For example, Sertraline and Fluvoxamine (Luvox) are FDA approved for pediatric OCD, and there is also good evidence for the efficacy in anxiety disorders (Sertraline was used in the Child/Adolescent Anxiety Multimodal Study) and some evidence for the efficacy of Sertraline for depressive symptoms. Additional considerations when selecting an SSRI include whether there has been a family history of response or lack of response to a particular medication. 

In most cases, SSRIs are well tolerated, and the most common side effects of SSRIs tend to be mild and/or self-limited (Miller & Campo, 2021). Common side effects of SSRIs include headaches, gastrointestinal discomfort, sedation or insomnia, sexual dysfunction, and dry mouth. Activation, which can present as insomnia, disinhibition, or restlessness, is more common in pediatric and adolescent patients than in adult patients. Activation more commonly occurs with higher starting doses and/or rapid dose escalation; this is one factor guiding recommendations to start at low doses and titrate gradually. More rare and severe in nature than activation is mania (symptoms can include markedly decreased need for sleep, irritability, expansive mood or grandiosity, or risky behavior); it is recommended that family history of bipolar disorder or mania be ascertained prior to starting medications. Other rare but serious side effects include serotonin syndrome, characterized by fever, hyperthermia, restlessness, muscle twitching, and confusion, and QTc prolongation most commonly associated with citalopram, for which an EKG should be considered. If side effects are mild, GLAD-PC guidelines recommend waiting 2-7 days to see whether they are transient. For persistent side effects, medication can be continued at the same dose if side effects are mild, or the dose can be reduced if side effects are moderate. 

Importantly, in 2004, the FDA issued a black box warning that antidepressants may increase the risk of suicidal thinking and behavior in youth up to age 24, particularly in the first month after starting medication. A subsequent meta-analysis of data from trials of antidepressant treatment in adolescents showed a small but significant risk difference of 0.7 percentage points for suicidal ideation or attempts between those receiving antidepressants compared to those treated with placebo. However, more recent studies have not found significant differences, and an additional consideration is the risk of suicidal ideation and behavior associated with untreated pediatric and adolescent depressive symptoms. 

Second Line Medications and Approaches When Initial Trial of Medication is Unsuccessful

As up to 40% of adolescents do not respond to initial medication treatment, the Treatment of Resistant Depression in Adolescents (TORDIA) study evaluated several approaches to this scenario, including switching to another SSRI or switching to another class of medication such as the Selective Norepinephrine Reuptake Inhibitor (SNRI) Venlafaxine. In this study, patients who switched to a different SSRI had similar responses to those who switched to an SNRI, and those receiving the SNRI reported more side effects. As such, it is recommended to switch to a different SSRI first rather than switch classes of medications. In cases where there is a partial response to medication, adding a second medication from a different class, or augmenting, is sometimes considered; however, there is less data for this strategy in pediatric populations compared to adult populations. Agents that are sometimes considered for augmentation include Bupropion, Lithium, and Atypical Antipsychotics. In these cases, consultation with a specialist is recommended. 

Other Relevant BHIPP Newsletters:

1. Combating Youth Depression with Behavioral Activation

2. Assessing Suicide Risk

3. Depression Screening Tools for Your Pediatric Primary Care Toolbox

Related Resources:

1. The REACH Institute has a GLAD-PC Toolkit to help primary care providers put the GLAD-PC guidelines into effect

2. Child Mind Institute resources on Medication for Kids With Depression and Treatment for Depression

3. The American Academy of Child and Adolescent Psychiatry has a Depression: Parents' Medication Guide

4. This Medscape article discusses Pediatric Depression Treatment and Management

As always, if you have questions about the behavioral health needs of your patients, we encourage you to call the BHIPP consultation line at 

855-MD-BHIPP (632-4477), open 9am-5pm Monday-Friday, for resource/referral networking or consultation support.

We will keep you informed about all our services and training events through our website ( and monthly e-newsletters. Additionally, BHIPP is on LinkedIn, Twitter, and Facebook. We invite you to follow us there to stay up-to-date on upcoming training events, pediatric mental health research, and resources for providers, families and children.


BHIPP Announcements

There is still time to register for the BHIPP ECHO Core Foundations Series before the first session!

Register for the BHIPP ECHO Core Foundations series! The first session will be held on November 1st from 8:00-9:00am. Join our multidisciplinary team of child behavioral health experts every month for virtual case-based learning and didactic presentations. This series is great for providers who want to improve their knowledge of child mental health and develop foundational skills. This series is held on the first Wednesday of every month from 8:00-9:00am between November 2023 and June 2024.Free CME and CEU credit is available for participation.

View Flyer
Register for the Series!

Sign up for the BHIPP ECHO Beyond the Basics Series!

Register for the BHIPP ECHO Beyond the Basics series! The second session will be held on November 9th from 12:00-1:00pm. Join our multidisciplinary team of child behavioral health experts every month for virtual case-based learning and didactic presentations. . This series is great for providers who have already participated in BHIPP ECHO, or who feel like they are experienced in treating behavioral health in their practice and are looking to explore advanced topics. This series is held on the second Thursday of the month from 12:00-1:00pm between October 2023 and May 2024. Free CME and CEU credit is available for participation.

View Flyer
Register for the Series!

Announcing the next BHIPP Resilience Break!

Register for our next BHIPP Resilience Break on November 17th at 12:00pm! BHIPP Resilience Breaks are a series of interactive, web-based learning sessions. These sessions are a virtual space for pediatric primary care and behavioral health providers to connect, learn and share about strategies, practices and resources to promote mental health and resilience among children and families as well as providers. Free CME and CEU credit is available for participation.

Register for this training!
BHIPP Bulletin Archive
Visit our website
Facebook  Twitter  Linkedin  Youtube  
BHIPP is supported by funding from the Maryland Department of Health, Behavioral Health Administration and operates as a collaboration between the University of Maryland School of Medicine, the Johns Hopkins University School of Medicine, Salisbury University and Morgan State University.

BHIPP and this newsletter are also supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $433,296 with approximately 20% financed by non-governmental sources. The contents of this newsletter are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS or the U.S. Government. For more information, visit

Copyright © 2021 Maryland Behavioral Health Integration in Pediatric Primary Care (BHIPP), All rights reserved.