Recognizing & Managing Adolescent Depression Materials

RECOGNIZING AND MANAGING ADOLESCENT DEPRESSION

ELLEN FELDMAN, MD

Dr. Feldman is a child and adolescent psychiatrist with 30 years in healthcare and 8 years in medical writing. She has worked in the Department of Behavioral Health, Altru Health System, Grand Forks, North Dakota, since 1998. Dr. Feldman has chaired the Department of Behavioral Health since 2010. Dr. Feldman is skilled in providing holistic, team-based care in various settings.

Topic Overview:

This paper presents a comprehensive review of up-to-date guidelines and evidence-based practices for the diagnosis, treatment, and management of depression among adolescents. Beginning with a brief overview of adolescence and developmental tasks during this critical time, the paper delves into epidemiologic data to highlight the widespread impact of this potentially debilitating disorder. The review outlines diagnostic criteria, common presentations, risk factors, and co-morbidities and thoroughly examines pharmacologic and non-pharmacologic evidence-based treatments. Clinical vignettes are incorporated throughout the paper. An emphasis on multi- disciplinary team involvement illustrates the vital role of interprofessional collaboration to achieve optimal patient outcomes.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist 0669-0000-24-011-H01-P

Pharmacy Technician  0669-0000-24-012-H01-T

Credits: 3 contact hour(s) (0.3 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $8.99

Estimated time to complete activity: 3 contact hour(s) (0.3 CEU(s)), including Course Test and course evaluation

Release Date: February 6, 2024 Expiration Date: February 6, 2027

Target Audience: This educational activity is for pharmacists and pharmacy technicians

How to Earn Credit: From February 6, 2024, through February 6, 2027, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Recognize the signs and symptoms of adolescent depression, including high-risk adolescent patients

Understand the role of screening tools in the diagnosis and management of depression

Review evidence-based pharmacologic and non-pharmacologic treatment strategies for depression

Review the multifactorial role of counseling and patient education, with a focus on common misconceptions about depression

Disclosures

The following individuals were involved in developing this activity: Ellen Feldman, MD, and Pamela Sardo, PharmD, BS. Pamela Sardo was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

© RxCe.com LLC 2024: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity

Introduction

Adolescence is a turbulent phase of life. This course begins with a concise discussion of the developmental tasks of adolescence. Subsequently, it delves into the epidemiology of adolescent depression, providing an overview of its prevalence and impact. Finally, the course focuses on exploring diagnostic criteria, risk factors, common comorbidities, and evidence-based treatments associated with depression in this age group, utilizing a patient example for illustrative purposes.

The Challenges of Adolescent Growth and Development

Adolescence is a period of life that spans the ages of 11 to 19. During this phase, the developing teen undergoes a visible and rapid surge of growth and transformation, driven by underlying shifts in physiologic, psychosocial, and cognitive functioning.1

Of profound concern is the link between adolescence and the onset of mental health challenges. Over 70% of adults with mental disorders trace the beginnings of their condition back to this period.2 Focusing on depressive illness, it is notable that 70 % of adolescents diagnosed with depression will have a recurrence within a mere five years. Such episodes can impede or delay the achievement of crucial developmental milestones characteristic of this age. As there is emerging evidence that prompt and effective treatment during adolescence may lessen this risk, recognizing and treating depression during these critical years is a priority.2,3

However, recent data paints a worrisome picture: depression during adolescence is increasing and remains a top cause of disability in this age group. Depression rates in the US doubled in this age group between 2009 and 2019, with girls particularly at risk. The COVID pandemic was associated with an exacerbation of this trend, with global data indicating up to 25% of adolescents (or 1 in every four teens) grappled with depressive symptoms.3-5

Depression in adolescents is rarely a straightforward matter. While it emerges from a complex interplay of biological, environmental, and psychosocial factors – similar to adults – the manifestation of symptoms often differs in younger individuals. Most importantly, treatment modalities tailored for teens are not as extensively studied as those for adults, making therapeutic options and clinical decision-making more nuanced and challenging.5,6

In this course, “depression” refers to major depressive disorder (MDD) as defined by the Diagnostic and Statistical Manual (DSM-5-TR) and/or the International Classification of Diseases 11th Revision (ICD-11). While these diagnostic tools contain symptom lists, it is crucial to understand that the treatment of depression goes beyond merely checking off symptoms. Accurate diagnosis, effective treatment, and long-term management of adolescent depression rely on a comprehensive patient history, physical examination, collecting collateral information from adult guardian(s), understanding the functional impact of symptoms, and, most importantly, building a strong patient-provider relationship.7,8

Take-home Message:

Adolescent depression is a public health priority, and girls are especially at risk.

Developmental Tasks of Adolescence in the Context of Medical Care

Adolescence is a critical period encompassing physical, cognitive, and psychological growth and development. While a comprehensive exploration of the developmental tasks during adolescence exceeds the bounds of this course, a rudimentary understanding of this phase equips medical providers with a foundation to develop strategies and approaches to work effectively with teenage patients.

During early adolescence, parents or guardians predominately steer the healthcare decisions for the teen. As this stage progresses, the young person gradually assumes a greater proportion of responsibility for their healthcare. For the health care providers, the challenge resides in developing and preserving a trusting and therapeutically sound relationship with both the adolescent and guardian(s) throughout this transitional period.9

Insight into the following tasks of adolescent development may help the provider:

Establishing identity: This includes the formation of values and beliefs. Teens seek to integrate the opinions of peers, as well as trusted adults in this process. Healthcare providers might encourage the adolescent patient to verbalize their own thoughts or feelings about depression treatment options instead of directing such questions solely to the adults responsible for them.10

Establishing autonomy: Often misinterpreted as “rebellion,” this stage fundamentally pertains to a desire for independence and self- reliance. Providers can honor this developmental task by ensuring patient privacy and involving the teen in the decision-making process.10

Establishing intimacy: This encompasses both physical and emotional connections. Providers should be cognizant of the significance and vulnerability of these early relationships when interacting with the teen patient.10

Developing body image: The onset of puberty brings bodily changes. Many teen patients are apprehensive about outside factors (for example, medications-induced weight gain) that could further usurp their control.10

Adolescent Scenario # 1

The following is a hypothetical case of a 16-year-old female diagnosed with depression, identified by the initials MC. MC enters the pharmacy to pick up antidepressant medication. Which of the following is the optimal response to the patient when observing she is about six weeks overdue for a refill?

“You have been missing pills - don’t you know that you must take these pills every day?“

“I will need to let your folks /doctor know that you are probably not taking this medication correctly.”

“Do you have a moment to talk about this type of medication – I am curious what you think about taking them, and I am here to help you develop a strategy to remember to take them if you are interested.

Nothing – since there is no guardian with MC so there is no use speaking directly to her.

Number three is the best response. This approach demonstrates an understanding of the emerging responsibility of this teen for her own healthcare decisions while also establishing a supportive and non-conflictual interaction. It integrates respect for her autotomy and provides an opening for establishing a conversational relationship, crucial for navigating through the delicate and significant developmental tasks of adolescence in the context of medical care.

Take-home Message:

As a medical provider, consider the age and developmental stage of the patient when providing therapeutic interaction.

The Scope of the Problem

Untreated depression in teenagers can profoundly affect their quality of life for years. The weight of depressive symptoms may hinder or alter typical adolescent milestones, including the ability to form and sustain social relationships, develop the ability to delay gratification, and successfully navigate the complex task of separating from parents.9,10

Throughout the 2000s, national surveys and international investigations consistently showed a spike in depression rates in adolescents. Daly (2022) looked closely at the results of eleven years of The National Survey on Drug Use and Health (NSDUH), which encompassed data from over 160,00 nationally representative US teens (ages 12 -17.) He noted that depression rates in the US among adolescents increased from 8.1% in 2009 to 15.8 % in 2019.4

Delving further into these results, Daly noted a significant gender disparity in the depression rates during these years. Female adolescents saw a 12-percentage point rise in depression rates compared to a 3.7% increase for their male counterparts. This trend held true across all age groups, races, ethnicities, and socioeconomic statuses, with the exception of black adolescents, where depression rates between males and females appeared to be in parallel.4

It is also worth noting there have been observations of a rise in depression rates among adolescents during and after the COVID-19 pandemic. A recently published meta-analysis by Wang, et al. (2022) incorporated eight studies looking at pre and post-COVID depression rates in adolescents. Although the methodologies among the studies were heterogeneous (making them difficult to compare), the consensus was clear: there was a significant uptick in depressive symptoms in teenagers following the COVID-19 pandemic.12

Adolescents with untreated depression are at higher risk for substance abuse, additional psychiatric issues, and even suicide.10,11 Ongoing research is probing into specific factors that may be driving the increased rates of depression. Social media exposure, a decrease in physical exercise, increased academic expectations, and parental mental health issues are all under examination as potential contributors.4,5,12

Take-home Message:

Rates of depression among adolescents are increasing; depression in adolescent years may delay developmental milestones and negatively impact adult quality of life.

Diagnostic Criteria

Symptoms of depression are delineated in two prominent guides: DSM- 5-TR and ICD-11. Both catalogs provide valuable insights into the symptoms and diagnostic criteria for depression but differ slightly in methodology and application. Notably, neither of these references is meant to diagnose as a stand-alone checklist; their optimal use is to guide an in-depth clinical interview.7,8

In both systems, the diagnostic criteria for a major depressive disorder in an adolescent is the same as for an adult; however, there are a few important distinctions which are discussed below.7,8

In the USA, most providers apply DSM’s diagnostic criteria but turn to ICD codes for billing purposes.7,8 Thus, a basic familiarity with each system is useful. To compare the diagnostic criteria below and included in Tables 1 and

2. These tables outline the specifics of diagnosing depression based on each system.

DSM-5–TR Major Depressive Disorder (MDD)

Under the DSM-5–TR, a Major Depressive Disorder (MDD) meets the following criteria:7

Five or more symptoms listed in the chart below have been present for at least two weeks; symptoms must include either depressed mood and/or irritability and/or loss of interest and/or loss of energy.

Symptoms result in a deterioration in functioning.

Symptoms are not better explained by another psychiatric disorder, are not due to the effects of a substance or pharmaceutical agent, and are not due to another medical condition.

There has never been a hypomanic or manic episode, and current symptoms do not meet the criteria for a mixed episode; if any of these are present, look towards bipolar disorders.

Table 1

DSM-5–TR Major Depressive Disorder (MDD)

ICD-11 Depressive Disorder

Depressed mood, irritability, or decreased interest in activities must be present for at least two weeks. Other accompanying symptoms may include the symptoms listed in Table 2. No history of manic, hypomanic, or mixed episodes.8

Table 2

Criteria for ICD-11 Depressive Disorder

Notably, the DSM-5-TR and ICD-11 diagnostic criteria overlap in multiple areas. Both systems emphasize the necessity of at least one key symptom: depressed mood or loss of interest/energy. In teens, irritability is added as many teens are unable to fully articulate the intense feelings of sadness experienced during a depressive episode. Instead, the teen exhibits a negative attitude, becomes irritated and argumentative, and then reacts with anger towards even small provocations.7,8,13

Take-home Message:

Irritability may mask an underlying depression in adolescence, look for the degree of functional impairment, and collect collateral information from family and school to obtain a full picture and make a precise diagnosis.

The persistence of these symptoms for at least two weeks and in sufficient severity to interfere with daily functioning is a mandatory criterion for both systems. The DSM-5-TR additionally stipulates the presence of at least five out of nine additional symptoms, whereas ICD-11 acknowledges other accompanying symptoms without specifying a count. It is important to note that a teen diagnosed with depression using DSM-5–TR criteria will likely fit the ICD-11 criteria as well, but the reverse is not always true.7,8

In general, there are several clusters of symptoms more likely to be prominent in depressed teens than in adults (and vice versa.) Changes in sleep, energy, and appetite are commonly seen in adolescents with depression, while their adult counterparts are more likely to present with a loss of interest and poor concentration.14

The DSM-5-TR and ICD-11 categorize depressive episodes as mild, moderate, or severe based on the number, type, and severity of symptoms, with a key focus on the level of functional impairment. For example, patients with mild depression may experience five – six symptoms but have a minimal change in functioning, while a patient with severe depression will typically describe more symptoms and will experience more significant interference with daily functioning. This nuanced understanding underscores the vital role of patient history in diagnosing and managing adolescent depression.7,8

Collateral information, from guardians and often from school personnel, is often necessary to paint a full picture of the onset of symptoms and their impact on functioning, including roles within the home, at school, and in social

settings. The path to comprehensive understanding may necessitate multiple visits to ensure a care plan finely tuned to the individual’s unique struggles.6,14

Screening and Risk Factors

Most mental health professionals and medical providers agree that treatment of depression during adolescence is important, but a major dilemma and disagreement in treating this disorder lies in the specific modality selected for intervention. The question is not “Should we treat?” but “How and when should we treat?”6,15

Adolescent Scenario # 2

Next, we introduce LW as an example of a teen patient presenting to a primary care clinic. LW is a 14-year-old, slightly overweight 8th-grade female who has been known to the provider for about eight years. She is generally healthy and presented today for an evaluation of excessive fatigue that has led to decreased school attendance. Her mother noted that LW’s grades have dropped slightly (from all A’s to mostly B’s), and teachers have commented that she seems more socially isolated and quieter than in prior years. LW snaps, “Well, don’t blame me- you’re the one who makes me go to school when I am just too tired.” At this, her mother turns to the provider and adds, “And she seems offended by everything I say.”

Recognizing depression in teens in a primary care setting is a complex task. Often, patients present with a guardian or parent who may be the person initiating the visit, while the teen may or may not have an interest in the proceeding. Depression screening tools, self-administered during routine visits, have been adopted to improve the recognition of depression in these settings.16

The US Preventive Service Task Force (USPSTF) is among several national medical groups recommending screening for depression in teens ages 12 and older. Furthermore, the USPSTF recommends that there be “adequate systems in place to ensure accurate diagnosis, effective treatment, and

appropriate follow-up.” This statement reflects the understanding that a diagnosis of depression may begin with screening but that screening alone cannot adequately diagnose or manage this condition.17,18

The Patient Health Questionnaire modified for adolescents (PHQ-9A) is the screening instrument of choice for many clinicians working with teens. This instrument is distributed without charge, is easy to use in an office or similar setting, and is self-completed within a few minutes. Each questionnaire allows one response per question, ranging on a scale from “not at all” to “nearly every day.” Scores reflect the likelihood of depression, with a score ranging from 5 to 27 representing the spectrum of mild to severe depression. A score >10 is specific for major depression in teens. It is essential to keep in mind that these tools and others like them must be used in tandem with a comprehensive history and physical – a screening tool alone cannot suffice for a depression diagnosis.16,19

Adolescent Scenario # 2, Continued

Back to LW: The provider glanced at the PHQ-9A LW completed in the waiting area and noted a total score of 9 largely due to endorsement of feeling “like a failure,” excessive sleep, and poor energy nearly every day. After silently reflecting on the developmental tasks of adolescence, including developing autonomy, the provider says to the mother, “How about if you give LW and me a chance to discuss what has been going on? I will be sure to call you in at the end of the visit so we can all review recommendations and answer any questions.”

With these statements, the provider is acknowledging the need for privacy for LW as well as the integral role her mother will most likely play in helping with treatment decisions. The screening results pave the way for a constructive conversation about depression and associated risk factors during the clinical interview. Extending genuine empathy (for example, “It must be tough to feel that way.”) without judgment helps build a therapeutic alliance. The provider can then delve deeper into some of the specific symptoms of concern.16,18

For example, the provider may ask LW to elaborate on items on the screen that she indicated happen on a frequent basis, specifically feeling “like a failure,” having poor energy, and poor sleep patterns. It is important to let LW know that she is entitled to confidentiality but that if she is endorsing suicidal thoughts, intent, or self-harming (or homicidal thoughts), this must be shared with a responsible adult (parent or guardian.)20

Risk factors significantly influence a diagnostic evaluation for depression. Risk factors in teens include a family history of depression, childhood maltreatment, history of exposure to trauma, bullying, a difficult relationship with parents, and identifying with a minority sexual identity. All these factors can shape the direction of the diagnostic interview. It is vital to highlight that, although there is controversy about the utility of routine screens for suicidal thinking in teens, depression increases the risk of suicidal thoughts, attempts, and completed suicide.4,15,21

Take-home Message:

Screens are often a first step toward a diagnosis of depression in adolescents and can help decide interview direction.

Differential Diagnosis and Comorbidity Other Types of Depression

In certain instances, patients may exhibit signs of depression that do not fit squarely within the criteria for MDD. Here, consulting the DSM-5-TR becomes an invaluable tool in discerning whether these patients align more closely with other depressive disorders such as Disruptive Mood Dysregulation Disorder, Unspecified Depressive Disorder, and the more subtle yet long- lasting Persistent Depressive Disorder.22,23

Comorbid Disorders of Mental Health

It is important to consider if there is a family history of bipolar disorder and recognize that a depressive episode in a teen may portend the onset of a bipolar disorder down the road. This is especially critical in decisions about treatment options, as some medications may potentiate the emergence of manic episodes in vulnerable patients.22,23

It is also noteworthy that more than 60% of teens with depression have a comorbid disorder of mental health. Consideration of other psychiatric conditions, notably anxiety, attention deficit disorder, and substance use disorders (SUD), is important when gauging functional impairment and determining treatment options. Other less frequent comorbid conditions include learning disorders, eating disorders, and somatic disorders.22,23

Anxiety often coexists with depression. More than half of depressed patients of any age may struggle with co-existing anxiety, a combination that can complicate recovery. Consequently, systematic screening for anxiety, especially in patients with poor treatment responses, is recommended to help unearth an underlying anxiety disorder. Utilizing a tool like the Generalized Anxiety Disorder scale can be beneficial in this regard. Keep in mind a negative anxiety screen has a higher predictive value than a positive screen. Like all screening tools, the value is maximized when paired with a diagnostic interview.22,23

Youth with depression may turn to the use of substances to help themselves feel better. Incorporating open-ended, non-judgmental questions about substance use in routine assessments of depressed teens can often lead to a more precise diagnosis. This, in turn, facilitates treatment plans targeted at both disorders. Collateral information (including drug screen) may be needed for accurate diagnosis if the teen is not forthcoming regarding substance use history.22,23

Medical Conditions and Medications

Lastly, be aware of the symptom overlap between certain medical conditions and depression. Several disorders, such as thyroid disease and anemia, can mimic the low energy and fatigue often seen in depression. Additionally, teens with chronic medical conditions such as inflammatory disease or neurologic disorders are more at risk for comorbid depression than healthy peers. The diagnosis can be challenging in this population because symptoms common in depression, such as fatigue, sleep disturbance, and poor concentration, may be intrinsic to the chronic medical illness or even a medication side effect. However, when symptoms such as feelings of guilt, low self-worth, or suicidal ideation arise, the concern for depression amplifies.22,23

A thorough assessment of history, physical examination, and pertinent diagnostic lab testing (such as complete blood count and thyroid-stimulating hormone) are instrumental in distinguishing these conditions.16,22,23 For those with recent changes in medications, a detailed evaluation of the timeline of symptom emergence and functional changes is especially pertinent. A multitude of drugs, such as beta-blockers, some oral contraceptives, and steroids, have the potential to induce depressive symptoms.16,22,23

Adolescent Scenario # 2, Continued

After LW’s mother leaves the exam room, the provider leans forward in a non-threatening manner, and says, “I know you’re mainly here for being too tired. But sometimes, our physical health is tied to how we feel emotionally. I notice on your screen that you have been feeling bad about yourself often, having low energy in addition to sleeping too much. Can we chat about this?” LM shrugs and looks away, but the provider notices her eyes well up with tears. “We don’t have to dive into anything you are not ready for,” the provider says. After a brief period of silence, LW hesitates and slowly rolls up her oversized sweatshirt sleeve, revealing a razor-thin superficial cut, scabbing over. “I don’t want to talk about this,” her voice quivers, “but I cut myself…and before you ask, I will tell you that I am not, like, trying to end it all or anything. I cut just one time last week because I felt so mad- and my friend said it

would help me feel better. I don’t want to do it again. And no, my mom doesn’t know.”

Take-home Message:

Consider comorbidities and a complete differential while maintaining an empathic, non-judgmental stance to help an adolescent verbalize emotional distress.

Evaluating Suicidal Risk

Suicide is the second leading cause of death among teens in the US and the third leading cause of death in this age group worldwide. Depression heightens the risk of suicide, suicide attempts, and self-harm, a serious aspect of mental health that should not be underestimated.16,22,23 Considering that many suicide attempts involve medications, it is understandable that pharmacists, as well as the PCP, will frequently encounter patients at risk for suicide. In fact, a 2019 study found that 22% of 500 community pharmacists surveyed knew a patient who had committed suicide, and 21.6% had received a request for a lethal dose of medication. Alarmingly, many clinicians feel unprepared to evaluate or respond to these high-risk patients.24

Even though patients may be reluctant to express thoughts about suicide directly, they tend to be more responsive to open-ended questions. Routinely asking patients with depression or depressive symptoms about suicidal thoughts, plans, or intentions can initiate a discussion.25

The National Institute of Mental Health (NIMH) provides a free resource, the Ask Suicide-Screening Questions (ASQ) Toolkit, on its website. The ASQ is a set of four screening questions (yes or no responses) regarding suicide intentions and thoughts. A positive answer to at least one of the questions is

highly specific to an elevated risk for suicide. This screen has been validated for children over the age of eight years old.26

Consider prompt referral for patients with high-risk factors and suicide intention to specialists. The availability of mental health providers can vary by region, and this invariably influences referral and consultation patterns. There is increasing evidence that collaborative care models – involving a team including the PCP, pharmacist, and other front-line professionals, as well as mental health specialists – can lead to more effective care for higher-risk patients with depression. Telemedicine, too, is showing promising efficacy and offers an opportunity to bring specialty care to communities previously lacking these services.27,28

Whatever the delivery method, it is important to have robust working relationships between primary care, community pharmacists, and local mental health providers. Providing patients with information about supportive resources, including support groups and services such as suicide hotlines, can create an additional safety net for these individuals.27,28

In this clinical vignette, LM is referring to non-suicidal self-injury (NSSI), which is a relatively common but destructive means of coping with strong emotions. Some studies have estimated close to 17 % of the adolescent population will engage in NSSI, while up to 75% of adolescents with a psychiatric disorder engage in these behaviors. While research continues regarding NSSI, it is clear that although NSSI is not suicidal in nature (and should be distinguished from such), this behavior is associated with a higher risk of suicide attempts down the road.29

A Word About Firearms

Clinicians may want to keep in mind the following facts when formulating a plan and direction with teens who self-harm or are potentially suicidal:

Firearms-related injuries are the leading cause of death for teens in the US; fatalities from firearm injuries have risen by about 44% in this

population since 2013. 59% of these are due to homicide, 37% from suicide and 3 % unintentional.31,32

Safe storage laws are associated with reduced self-inflicted and homicidal firearm fatalities in youth. There is evidence from several trials that counseling about the safe storage of firearms combined with providing a safe-storage device increases the probability of safe firearm storage (association with safe storage is stronger with both interventions than either one alone.31,32

Alcohol and drug use raises the risk of firearms fatalities and injuries for all ages.33

Repeated studies have shown firearm access is the highest risk factor for teen firearm injuries. In 80% of teen firearm suicides and 90% of unintentional teen firearm fatalities, the gun was obtained from the home of the teen or the home of a relative.34

Most suicide attempts are impulsive, and decreasing access to lethal means of suicide during times of emotional upheaval or crisis (known as lethal means counseling) can be effective in the prevention of completed suicides.31,35

Adolescent Scenario # 2, Continued

LW responds in the negative to all the screening questions in the ASQ, rolling her eyes and saying, “I told you I am not suicidal.” When asked, she

does note that her parents have guns in the home, saying, “We hunt. But the guns are usually locked.”

The provider notes, “The gun part and the cutting worries me; we will need to discuss safety steps when we bring your mom back. But I’m glad you’re not suicidal. I want to follow up on what you said about cutting when you feel angry –and that you want to stop doing this. I would like to help you plan to stop – can you identify what makes you so angry?” LW sighs, “Mostly feeling alone- like nobody likes me,” she says, “and I guess when I hear my parents arguing about why I didn’t go to school…do you have to tell my mom- about the cutting, I mean? I think she’ll be really disappointed in me.”

Take-home Message:

Always evaluate risk factors for suicide, including the availability of firearms and other destructive tools.

Building and Maintaining a Therapeutic Alliance

Depression is a recurrent, chronic disorder. As such, management of depression in primary care follows the model of management of other chronic conditions. Monitoring symptoms, function, side effects (from any prescribed medications), and treatment adherence is ideally accomplished by establishing a team with representation from multiple disciplines, including primary care, behavioral health, pharmacy, and nursing working together with the patient.3,6,15,23

When working with teens, it is important to develop an approach that balances the delicate task of building and maintaining a therapeutic alliance with the adolescent patient while acknowledging the important role of the parent or guardian in treatment planning and decision-making. A non- judgmental stance from a primary care provider or member of a pharmacy

team can assist in this process. Education regarding understanding depression as a medical illness and even comparing the diagnosis and treatment of depression to other less stigmatized childhood chronic disorders (such as asthma or diabetes) may help the child and family accept both the diagnosis and treatment recommendations.3,6,15,23,36

Adolescent Scenario # 2, Continued

The provider reassures LW that although her mother needs to know about the cutting, the two of them can tell her together and present the information in a factual manner. “Getting help with this is why you are here,” says the provider, “We can all work together to address your tiredness and the anger that has been so hard to handle alone.” “Maybe,” says LM, “if you think you can help. But can we not talk about this anymore today?” Before calling in LM’s mom, the provider makes sure to complete a basic physical examination, including vital signs, looking for enlarged lymph nodes that could indicate infection, and a skin assessment (making sure the cuts aren’t more extensive than LW reported).

It is not unusual to have incomplete information when dealing with teens, especially given limited time for office visits. The results of the screen (low self-worth, low energy, excessive sleep), the mother’s observation of increased irritability, the teacher’s observation of social withdrawal, the drop in both school attendance and grades and LW’s statements all point towards a diagnosis of depression with moderate functional impairment.

Ruling out other medical causes for the fatigue, evaluation of other factors, including obtaining a substance use history, and understanding a timeline of symptom development will be essential in making the diagnosis and tailoring treatment.3,6,15,23,36

Symptom Severity and Functional Impairment

Considering the severity of symptoms and functional impairment, a consultation or referral to a mental health clinician is the most appropriate path. In many communities, access to mental health resources will take days, if not longer; thus, an immediate step must include safety planning.36,37

LW and the provider should tell her mother about the cutting and develop an initial plan to stop it. This is an important first step. Both acknowledge LW’s expressed desire to stop cutting and help establish safety at home. Opening the lines of communication between LW and her mother expedites this process.

Firearms: Emphasize with her mother a firm recommendation to secure all firearms, keep ammunition separate, and strongly consider removal of firearms from the home. Remind mother that teens are frequently impulsive. LW’s acknowledgment of having difficulties managing strong emotions (“…I get mad a lot”) and actions of self-harm elevate the risk of allowing her exposure to unsecured firearms.

Adolescent Scenario # 2, Continued

LW turns away from her mom when she enters the room, then takes a deep breath and turns to her, saying softly,” I’m really sorry. I have to tell you I cut myself- just a little.” Her mother nods slowly and turns to the provider, “I was worried about this. Thank you for encouraging L to tell me.” Then she turns to her daughter, “What can I do to help?” she asks. The provider facilitates the development of a safety plan – LW readily agrees to remove razors from her room and go to her mother if she feels like cutting (“But don’t ask me what is wrong! I don’t always know.”) Her mother agrees to be available, remove all firearms and talk with LW and her father about a

realistic plan for school attendance to get them all on the same page and avoid some agreements. “But what about medications?” asks the mother.

Take-home Message:

Understand the role of the parent or guardian in treatment planning and decision-making for teens and take this into account when building a therapeutic relationship with the teen patient.

Pharmacotherapy, Psychotherapy, Lifestyle Changes How to Choose an Effective Treatment Plan

Evidence-based guidelines for the treatment of depression in primary care suggest targeting the initial approach according to the severity of the presentation. Psychotherapy and lifestyle modifications are recommended for mild cases, while pharmacotherapy is generally recommended for more severe cases or when initial symptoms do not respond adequately. One rationale for these differences in treatment is that the effectiveness of antidepressants varies based on the severity of symptoms, with smaller effects observed in cases of mild depression. It is important to note that the severity of functional impairment is the most important factor when determining the severity of the overall condition and appropriate treatment intensity.3,6,15,23,36

Research into effective treatment for adolescent depression is ongoing. Evidence points to enhanced treatment efficacy when intervention is within a primary care clinic integrated with behavioral health resources, but this is not universally available.38

Pharmacotherapy and psychotherapy are perhaps the most researched treatment modalities in this field. More research is emerging, however, on lifestyle modifications such as optimizing diet, regulating the use of social

media, and increasing physical activity. The choice is rarely simple or binary and must take into consideration the attitude, beliefs, and concerns of both the teen patient and decision-making guardian(s).23,36

A typical first recommendation for any teen with depressive symptoms is to restore a healthy sleep schedule, get back to a regular daytime routine including physical activity, and eat and socialize in a healthy manner. A parent or guardian is usually enlisted to aid in this regard. If depression symptoms are mild, a trial of psychotherapy is generally recommended. For moderate to severe depression or if mild symptoms do not respond to psychotherapy after six to eight weeks, psychotherapy and medication are usually combined.23,36 The challenge here is choosing an effective treatment plan that may combine all three approaches.

Pharmacotherapy

Two selective serotonin reuptake inhibitors (SSRIs), fluoxetine (Prozac) and escitalopram (Lexapro), are the only medications approved by the Food and Drug Administration (FDA) for the treatment of depression in adolescents. Other SSRIs, such as citalopram, and other agents, such as selective norepinephrine-reuptake inhibitors (e.g., venlafaxine (Effexor)), are commonly prescribed “off-label” to this age group as well. Off-label use is not unusual in pediatric practices but merits a clear explanation to the teen and family.23,36

A special note about the SSRI paroxetine (Paxil) is indicated. Studies from the early 2000s and again in 2015 showed poor efficacy and potentially dangerous adverse effects (including the emergence of suicidal thoughts) associated with the use of this agent in the treatment of adolescent depression.39

When initiating SSRI treatment, is imperative that both the patient and guardian understand that medications for depression take time to show an impact – typically at least four weeks and often six to eight weeks for maximum benefits. For an impatient, live-in-the-moment teen, this can feel

like an eternity. Without education, many will stop the medication well before this time. The pharmacy team is in a prime position to provide and/or reinforce this message verbally and even may want to place an auxiliary label on the bottle of pills indicating the need for compliance.23,36,40

Educational points include the following:

The medication will take effect slowly, over at least one month. However, there are interventions a teen should begin right away, such as adopting a regulated wake/sleep schedule, healthy eating, regular physical exercise, avoid substances of abuse.23,36,40

A course of medication for the treatment of depression in teens lasts from six months to a year from symptom relief. Frequent appointments will occur over this time to check medication compliance and watch for any changes (such as re-emergence of symptoms).23,36,40

Avoid early discontinuation of medication.23,36,40

Make sure to discuss an endpoint for the medication as well – these should not be lifelong medications for most teens.23,36,40

Common side effects: headache, changes in sleep (insomnia or sedation), gastrointestinal distress, and dryness in mouth and/or eyes. These are usually transient and often addressed with changes in dosing or timing if warranted. Because pharmacy technicians are often the pharmacy professionals that the patient interacts with, if a pharmacy technician notices an adolescent patient purchasing an over-the-counter product for headaches, an OTC containing caffeine, an OTC sleep aid, or drops for dry eye drops (with their antidepressant characteristics), it may be appropriate for them to notify the pharmacist.23,36,40

Warn about the possibility of activation, mania, and/or emergence of suicidal ideation. (See below for a discussion on each.)23,36,40-42

Other Notable Side Effects

Activation, referring to disinhibition or decreased self-regulation, is a serious side effect that occurs more often in adolescents than in adults using these agents. Activation is more likely to occur with rapid dose escalation and at higher doses; keeping doses low enough to be effective and advancing with moderation is recommended. This phenomenon is distinct from the small potential risk of antidepressants leading to a manic event in vulnerable adolescents.40

Another potentially serious side effect of medications used to treat depression in adolescents is the emergence of suicidal ideation. In 2004, the FDA issued a boxed warning (indicating the highest safety-related concerns) regarding the small but still significant risk of increases in suicidal thinking and behavior in adolescents taking antidepressants. A 2018 updated systematic review found similar rates of treatment-emergent suicidality in patients receiving antidepressants and placebo. Nevertheless, patients and families must be cautioned to be alert to the possibility of elevated suicidal thoughts while starting and changing doses of an antidepressant.41

Finally, many of the SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) possess potential drug-drug interaction profiles. Additionally, certain agents within this class may influence blood pressure parameters (e.g., duloxetine may transiently elevate blood pressure)42 or decrease the seizure threshold e.g., bupropion).43 It is imperative for all pharmacy team members to thoroughly review the prescribing information for each medication and maintain familiarity with its details.

Typical Course of Treatment

Only about 60% of adolescents treated with an SSRI for depression will show an adequate response. Evidence from multiple trials points to the next step as either a switch to a different SSRI (assuming a time course of at least six to eight weeks and dose adequate) or a trial of an SNRI such as venlafaxine (Effexor). However, in the Treatment of Resistant Depression in Adolescents

study, adding cognitive behavioral therapy with the new antidepressant was associated with the most improvement in depression scores.40,46

A common practice clinically is to add a second medication if (after six to eight weeks) there is only a limited response to the initial medication. Agents such as bupropion, atypical antipsychotics, or lithium are used in this manner, although medical evidence for the safety and efficacy of this approach in teens is lacking. In general, referral to specialty care is the most prudent course at this point in treatment.40,44

A 2021 Cochrane review focused on response rates associated with newer antidepressants, such as vilazodone (Viibryd) and desvenlafaxine (Pristiq), in children and teens with depression. This comprehensive meta- analysis found that “most newer antidepressants may be associated with small and unimportant reductions in depression symptoms compared with placebo, which raises the question of whether they should be used at all.” However, the reviewers did indicate that the heterogeneity of included trials limits confidence in broad conclusions. Additionally, low to moderate evidence was found for the efficacy of some of the first-generation antidepressants, including fluoxetine (Prozac), escitalopram (Lexapro), sertraline (Zoloft), and also duloxetine (Cymbalta).45

Ketamine as a Pharmacotherapy in Adolescents

There is limited data that ketamine may be an effective drug for treating depression in adolescents. This NMDA receptor antagonist is used in treatment-resistant depression and in addressing acute suicidal intentions in adults, but has limited data showing safety and efficacy in rapid resolution of suicidality and depression in adolescents. There are several published case studies involving intravenous administration of ketamine in severely depressed adolescents that show promise for this intervention. Research directions include a better understanding of the potential for harm, side effects, and optimal delivery method.46

Psychotherapy

Cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) are the two types of talk therapy with the most data for efficacy in the treatment of adolescent depression. Both therapies may be delivered individually or in a group setting by trained professionals and typically have a prescribed number of sessions. Online delivery is a recent trend, with positive emerging data.23,36,47,48

The focus of CBT is on thoughts and feelings that may impact behaviors and perpetuate depressive symptoms. Adolescents are taught to examine assumptions (for example, “nobody likes me, so I will never have friends”), look at these objectively, and attempt to reframe them in a positive light. Homework involves developing self-awareness and self-examination.36,47,48

Interpersonal psychotherapy, on the other hand, involves a focus on relationships and interactions. This technique teaches communication and problem-solving skills with an eye on helping patients recognize emotional responses and build healthier relationships.36,47,48

Often, the choice of therapy is determined by availability in the community. Studies have pointed to IPT being more effective than CBT in teens with depression when parent-child conflict is prominent and when peer

relationships are problematic. Cognitive behavioral therapy seems more effective than IBT when anxiety is prominent. Both therapies show reduced efficacy in teens who presented with severe depression, highly suicidal intentions, and significant hopelessness.36,47,48

Lifestyle Changes

Emerging evidence supports lifestyle changes as a treatment for adolescent depression. These include physical activity, management of screen time on social media, and dietary changes.

Physical Activity: In a recently published meta-analysis covering 21 studies and over 2000 youth, physical activity interventions showed a significant short-term benefit for children and adolescents with depressive symptoms (versus other disorders of mental health) Notably, few studies continued past 22 weeks, and in the four studies that did look at long-term remission, the association was not sustained. However, the initial findings were strong enough to warrant additional research into this link.49

Social Media: A 2023 systematic review of 50 studies looking at “screen time” and mental health in teens found a correlation between increased social media usage and decreased mental well-being in adolescents of both genders and more significant depression in girls. Follow-up and further research in this area is continuing.50

Nutrition: A 2019 systematic review of over 50 studies found strong evidence of an association between quality of diet, risk of depression, and possibly amelioration of depressive symptoms. Specifically, diets rich in ingredients such as olive oil, fish, nuts, fruits, and vegetables showed an inverse relationship with depression in teens. Ongoing nutritional research is looking at diet and nutrition as modifiable risk factors for this disorder.51

Take-home Message:

With only two medications FDA-approved for adolescent depression, off-label use is common. Be aware of the relative risks and benefits of standard treatment (antidepressants and/or psychotherapy) in adolescents as well as the potential of adjunct treatments.

Summary

Adolescent depression is a prevalent and serious health issue with potential long-term consequences; timely identification and intervention can help alleviate the impact.

The criteria for diagnosing depression in adolescents align with those for adults; however, the manifestations can vary, with heightened irritability a frequent hallmark in teens. Gathering collateral information is crucial.

Effectively utilize adolescent-specific depression screening tools (such as PHQA) and ensure comprehensive follow-up interviews are conducted to delve deeper into the screening responses.

Differential includes distinguishing depressive symptoms from medical disorders, medication side-effects, and other disorders of mental health while also considering the potential for co-occurring disorders, including anxiety and substance abuse.

Evaluate the risk of suicide carefully and engage supportive adults within the teenager’s living environment to eliminate access to firearms and other potentially dangerous items.

Treatment options include pharmacotherapy, psychotherapy, and/or lifestyle modifications. The choice of treatment should be influenced by the level of functional impairment, relative risks and benefits as well as the perspectives and concerns of the patient and parent/guardian. Combining different treatment options may be beneficial.

Course Test

An adolescent patient should

have no input into treatment decisions. Decisions are up to the responsible adult.

be treated with the understanding that the teen is in the process of becoming an adult, striving for autonomy while still needing adult guidance and input.

be treated with the understanding that teens are often rebellious and not entitled to privacy in healthcare.

never be addressed directly in a healthcare setting; instead, all questions should be filtered through a responsible adult.

Adolescent depression

is fundamentally different from adult depression, with a distinct set of diagnostic criteria stemming primarily from childhood trauma.

has diagnostic criteria, etiology, and presentation that are exactly the same as adult depression.

has diagnostic criteria that align with criteria for depression in adults, but presentation often differs, with irritability a hallmark in adolescent depression.

is not well defined, etiology is unknown, and there are no evidence- based diagnostic criteria.

Depression in adolescents

is considered a normal and expected part of development.

occurs equally in girls and boys; risk factors include a family history of depression and impaired intelligence.

is more common in boys than in girls; risk factors include playing violent video games.

occurs more commonly in girls than boys; risk factors include a family history of depression and being a victim of bullying and /or abuse.

Screen for depression

in all teens ages 12 and up, using an age-adjusted screening tool and be prepared to follow up with an interview and appropriate resources.

only in teens with a family history of depression, and it is recommended to use the same screening tools that are used for adults.

in all teens ages 12 and up, using the same screening tools that are used for adults; refer out any teen who scores above a specified cut-off level.

after the teenage years because of the high rate of false negatives.

When considering medication for adolescent depression

never discuss the boxed warning for SSRIs with the teen, as this may implant ideas.

make sure the teen and parent understand that if they do not see an antidepressant effect from the medication within two weeks, the medication will not work.

discuss that SSRIs may take time (at least one month) to show a response.

discuss that SSRIs are rarely effective in teen depression and should be avoided.

The following medications are FDA-approved for the treatment of adolescent depression

fluoxetine( Prozac) and bupropion (Wellbutrin)

bupropion (Wellbutrin) and venlafaxine (Effexor)

escitalopram (Lexapro) and venlafaxine (Effexor)

fluoxetine (Prozac) and Escitalopram (Lexapro)

Cognitive behavior therapy and interpersonal therapy

must be combined with medication to be effective in the treatment of adolescent depression.

are less effective in highly suicidal teens.

are only delivered individually and in person.

have little data supporting the use of these therapies in the treatment of depressed adolescents.

An evaluation for depression in an adolescent

should include an inquiry about suicidal thoughts and/or self-harm; when positive, a safety plan (including parents/guardian) and securing potentially dangerous items is necessary and appropriate.

should include an inquiry about suicidal thoughts and/or self-harm; if positive, safety planning should occur with the teen and not involve family members due to confidentiality constraints.

should never include an inquiry about suicidal thoughts and/or self- harm; these questions are frightening to a teen and may cause a teen to think about suicide.

should never include an inquiry about suicidal thoughts and/or self- harm; wait for the teen to broach this on their own, as this will naturally happen during an interview.

There is relatively strong evidence for the following treatment of adolescent depression:

Implement specific diets and decrease screen time, especially time spent on social media.

SSRI and bupropion.

increasing physical activity and ketamine for severe depression.

use of SSRIs (FDA-approved or “off-label”) and cognitive behavioral therapy (CBT) or interpersonal therapy (IBT).

When starting an adolescent on an SSRI for depression, which of the following statements describes the correct discussion approach?

Discuss with the adolescent and parent/guardian that there will be at least one month until symptom relief and begin interventions such as sleep regulation, healthy eating and physical exercise immediately.

Discuss with the adolescent and parent/guardian that the medication will take effect almost immediately, and once it does, the teen will begin to regulate sleep, eat better, and increase activity.

Only talk to the parent/guardian and let them know there will be at least one month until symptom relief and to begin interventions such as sleep regulation, healthy eating, and physical exercise immediately.

Only talk to the adolescent that the medication will take effect almost immediately, and once it does, the teen will begin to regulate sleep, eat better, and increase activity.

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