Clinical practice guidelines for the management of depression in children and adolescents

INTRODUCTION Over the last half century, it is now well established that depression can occur at any age, and it has been documented as early as infancy. In terms of epidemiology, different studies which have evaluated the prevalence of depression in children and adolescents suggest that the prevalence varies according to the different age groups. Prevalence figures reported for infants vary from 0.5% to 3% in clinic population, whereas in preschool children, the prevalence rate for major depression (1.4%) has been reported to be higher than depression not otherwise specified (0.7%) and dysthymia (0.6%). Studies done in community settings suggest the prevalence of depression in children to range from 0.4% to 2.5% and among adolescents to be from 0.4% to 8.3%. Lifetime prevalence through adolescence is considered to be as high as 20%. Prior to puberty, depression is known to have equal gender representation; however, among adolescents, the male: female ratio is 1:2. Over the years, it has also been understood that depression in children and adolescents is a chronic and relapsing condition, which does not remits spontaneously and hence, there is a need to identify and treat the same at the earliest to reduce its long-term negative consequences. Childhood depression has been shown to lead to an increased risk of poor academic performance, impaired social functioning, suicidal behavior, homicidal ideation, and alcohol/substance abuse. It is also associated with an increased risk of recurrent depressive episodes. Unfortunately, a major proportion of depression in children and adolescents is underdiagnosed and undertreated. SCOPE OF THE GUIDELINES The Indian Psychiatric Society published clinical practice guidelines for the management of depression in children and adolescents for the first time in the year 2007. Over the years, more research has accumulated in this area, and hence an effort is made to update the previous version of the clinical practice guidelines. These guidelines intend to provide a broad framework for the proper assessment and management of depression in children and adolescents. It is recommended that these guidelines must be read with the previous version. These guidelines must not be considered as a substitute for the professional knowledge and clinical judgment of the treating psychiatrist. It is important to remember that these guidelines are not applicable to any specific treatment setting and will require minor modification to suit to the needs of the children and adolescents in various treatment settings. Accordingly, the recommendations made as part of this guideline may have to be tailored to the needs of the individual patient. ASSESSMENT OF DEPRESSION IN CHILDREN AND ADOLESCENTS Assessment of depression in children and adolescents involves establishing the diagnosis; evaluating comorbid conditions; considering all the possible differential diagnoses; and evaluating psychosocial issues contributing to the development and continuation of depression such as family discord, family psychopathology, suicidal risk, and the ensuing dysfunction. It also involves developing a good therapeutic alliance with the children and adolescents and their family members and making decision about treatment setting and patient's safety. Assessment needs to be understood as an ongoing process and patients may have to be assessed regularly, as per the need and phase of the treatment [Table 1].Table 1: Assessment of children and adolescents presenting with depressionHistory Taking: The complete psychiatric evaluation should include a history of the present illness and current symptoms; evaluation for symptoms of mania or hypomania, taking history, and evaluation for general medical conditions; evaluation for a history of substance use disorders; evaluation for a personal history (e.g., psychological development, response to life transitions, and major life events); evaluation for a social, educational, and family history; and a review of the patient's medications, past treatment history, physical examination, detailed mental status examination, and diagnostic tests as indicated. In general, for identification of depression in children and adolescents, it is better to collect information from all the possible sources, i.e., report and observation of patients, parents, peers, siblings, and teachers during the clinical interview. It is important to remember that the child and parents or other caregivers need to be interviewed separately and also together. Usually, more than one interview may be required to get the complete picture of depression. It is suggested that evaluation of children with depression should involve interview of both the parents and the child. Differences are noted in the parent reports and self-reports of depressive symptoms. Parents more often report externalizing symptoms such as irritability, whereas children themselves more often report internalizing symptoms such as low mood. During assessment, developmental perspective needs to be taken into consideration and besides the routine mental status examination, play techniques can be used as part of the assessment. It is reported that, compared to healthy and nondepressed children, preschool children with depression depict significantly lower symbolic play and more often indulge in nonplay behavior such as exploration of toys and interaction with the examiner. Children with depression also demonstrate less coherence in their play. Diagnostics and Clinical Features: As per the prevailing nosological systems, i.e., Diagnostic and Statistical Manual, fifth revision (DSM-5) and International Classification of Diseases, 11th Revision, depression must be diagnosed in children and adolescents by using the same diagnostic criteria, as used for other age groups. The DSM-5 suggests that the criteria of "presence of depressed mood" can be replaced by "irritable mood" in children and adolescents. The diagnosis of persistent depressive disorder (equivalent of dysthymia) requires duration of 1 year in contrast to the 2-year duration required for adults. However, it is considered that the criteria given in the DSM do not address the developmental variations in symptom manifestations, and hence it is required to modify the criteria to pick up depression in children. It is suggested that depression in infants may manifest as failure to thrive, severe psychomotor delay, apathy, sad facial expression, and lack of responsiveness to alternative caregivers. It is also important to note that, in view of the level of cognitive development, younger children may appear sad but may not be able to verbalize the same. Instead, these children may have irritability, which may manifest as frustration and temper tantrums and behavioral problems. Other symptoms indicative of depression in children include increased rejection sensitivity. Certain cognitive symptoms such as low self-esteem, hopelessness, and depressive guilt, which are seen in patients with depression in other age groups, may not be apparent in children with depression because of lack of cognitive development (i.e., lack of development of abstract thinking). The concern about the future (hopelessness) is more strongly associated with depression in adolescents than in children, whereas guilt is more often seen in children than for adolescents. According to the current DSM criteria, patients with depression may have either an increase or a decrease in appetite/weight from usual. However, it is important to remember that children will have normative increase in appetite and weight and due to this, the utility of increases in appetite or weight as a clear feature of depression in youth is questionable. It is suggested that, although decreases in appetite and weight are associated with depression in children and adolescents, increases are not. It is also suggested that strict application of 2-week duration criteria may also not be appropriate to very young children. Evidence suggests that preschool children meeting all criteria for major depressive disorder (MDD) independent of the duration criteria exhibit higher levels of MDD symptoms and functional impairment than controls. Hence, some of the researchers suggest that, rather than focusing on the presence of persistent mood symptoms for 2 weeks, in children and adolescents, the clinicians should focus on the presence of symptoms for "most days than not." Besides the DSM criteria, evidence suggests that younger children with depression more often manifest with somatic symptoms (headache, abdominal pain, and general aches and pains), anxiety features (separation anxiety and phobias), restlessness, and psychotic symptoms such as hallucinations. Adolescents with depression often report symptoms of anhedonia, boredom, hopelessness, increased sleep, weight change (including failure to reach appropriate weight milestones), substance use including alcohol, and suicide attempts. In children, when psychotic symptoms are present as part of depression, these commonly manifest as auditory hallucinations. Adolescents with depression usually report psychotic symptoms in the form of delusions. It is important to note that, compared to adults with similar manifestations, the risk of bipolar disorder is higher among children and adolescents who manifest psychotic symptoms. Adolescents may also manifest with seasonal affective disorder. Considering the difference in manifestation and developmental or age-specific symptoms, it is suggested that assessment of depression in children and adolescents should cover the acronym "DUMPS." "D" stands for the evaluation of duration of symptoms, depressed mood, defiance and disagreeability, and distant or withdrawal behavior. "U" stands for the presence of undeniable drop in educational performance/grades or interest in school, which is seen quite frequently in young children. Drop in educational attainments arises due to poor concentration, lack of ability to make decisions, loss/lack of interest, and poor motivation for doing activities that were pleasurable earlier. Accordingly, it is suggested that report cards of previous years should be reviewed as this can help in recognizing the beginning of decline of grades, or fluctuations with certain seasons (e.g., a drop every winter). Poor concentration and an inability to complete the work may be particularly a major issue in high school going attending adolescents, whose school work mainly involves writing, doing laboratory assignments, reading and answering questions, etc. Children who fall behind in their class often start missing classes or avoid going to school. Accordingly, school avoidance should be an alarm for the evaluation of depression. "M" stands for morbid and strange behavior which may be actually an indirect manifestation of suicidality. "P" represents pessimistic attitude, which is commonly seen in children and adolescents with depression. "S" represents somatic symptoms, particularly abdominal pain and headaches, which are common in young people. Evaluate for comorbidity In general, it is said that comorbidity is a rule rather than the exception in children and adolescents with depression. The commonly seen comorbid conditions include anxiety disorders, substance use disorder, personality disorder, conduct disorder, oppositional defiant disorder, attention-deficit hyperkinetic disorder (ADHD), and dissociative/conversion disorder. The high comorbidity is attributed to the common environmental etiological factors and shared genetic influences between depression and most of the common comorbid disorders. Consider the possibility of the underlying medical cause As in other age groups, it is important to evaluate whether the depressive symptoms can be attributed to medical illnesses or other psychiatric disorders. The common medical illnesses and psychiatric disorders which need be considered for differential diagnosis are summarized in Table 2. In addition, due importance must be given to the intake of medications as many medications are known to cause depression [Table 2]. In case the symptoms can be better understood and attributed to a medical illness, then the diagnosis of MDD is not appropriate. Organic diseases, such as hypothyroidism, metabolic abnormalities, and space-occupying lesions, need to be ruled out in every infant who has depressive symptoms. Considering the fact that depression may be attributed to various physical illnesses, a through physical examination must be carried out in all children and adolescents presenting with depressive features. In case any physical illness is suspected, help of pediatrician and other specialist as per the requirement may be taken. At times, it is difficult to identify depression in the presence of a medical disorder, especially when the medical disorder is associated with sleep disturbance, change in appetite, somatic symptoms, and lethargy/loss of energy. In such a scenario, clinicians should look for ideas of guilt, hopelessness, helplessness, worthlessness, and self-harm including suicide, which are unlikely to be due to a medical disorder. When present, these features are suggestive of diagnosis of MDD. Depending on the need, various investigations must be carried out.Table 2: Differential diagnosis for depression in children and adolescentsConsider the possibility of Bipolar Disorder It is important to consider bipolar disorder in the differential diagnosis as use of antidepressants in a child or adolescent with undiagnosed bipolar disorder can lead to switch/behavioral activation. A possibility of bipolar disorder needs to be considered, when the children and adolescent with depression have psychotic symptoms, marked psychomotor retardation, reverse neurovegetative symptoms (increased sleep and appetite), irritability, and a history of bipolar disorder in the family. Consider other psychiatric disorders in the differential diagnosis Efforts must be made to rule out various psychiatric disorders by focusing on the longitudinal course of the symptoms, presence of other core symptoms of various disorders, and severity of symptoms. Further, it is important to remember that many of the psychiatric disorders, considered as differential diagnosis, also co-exist with depression. Assessment for suicidal behavior One of the most important aspects of assessment of children and adolescents with depression includes the assessment of suicidal risk. Clinicians should not underestimate the risk of suicidal behavior in children and adolescents. Clinicians should ask about the presence of suicidal ideation, specific plans for self-injury, and any history of actual self-harm or overt threats or gestures. Empirical data suggest that careful inquiry often helps to identify unsuspected suicidal ideation or acts. Developmental perspective needs to be taken while evaluating suicidal behaviors in prepubertal children, and attention must be paid to the child's own concept of death, as, at times, children do not view death as irreversible. This lack of understanding of irreversibility, in some cases, may actually increase the risk of a suicidal attempt. Inquiry can be started with questions like "Do you ever feel things are so bad that you wish you were dead?" and "Do you ever feel like wanting to hurt yourself or do anything to kill yourself?" If the patient responds as yes to any of these queries, further assessment can include questions like "Have you ever done anything to hurt yourself or to try to kill yourself?" If response to these questions is in affirmation, then further assessment should focus on the actual committed act, i.e., what was done, what precipitated such act, and what was the outcome of such an act. Motivation and intent of any previous attempt need to be assessed, and the important fact to remember is that it is not the method per se, but the understanding of lethality is more important. Risk factors for repetition of the act and completed suicide include a history of multiple attempts in the past, persistent suicidal ideation, and high intent. Other factors which need to be assessed include psychological and interpersonal factors, family and interpersonal issues, physical and psychiatric comorbidities, chronicity of depression, evidence of risk-taking behaviors in the past, impulsivity, aggression and hostility, presence of commanding auditory hallucinations asking the child to hurt or kill him or her, and history of physical and sexual abuses and failure (in examinations and love). Assessment of suicidal risk is not complete without the inquiry about the available lethal means (potentially lethal drugs, access to guns) because such means magnifies the risk of completed suicide. Evaluate the level of dysfunction Dysfunction assessment needs to cover the academic performance, family functioning, and peer relationship. Evaluate the support system Child's support system forms the backbone of the treatment plan. While assessing the support system, the fact to be kept in mind is that it is not the number which matters, but it is the comfort level of the child with that adult which matters. At times, although both the parents may be around, one may be overcritical and the other may be sulking his/her guilt. Accordingly, depending on the need, the parents or significant others may require evaluation for psychiatric morbidity. Use of rating scales Routine clinical assessments may be supplemented by standardized rating scales, depending on the feasibility. Investigations The list of investigations is usually guided by the assessment. In general, neuroimaging is not indicated in children and adolescents with depression. However, neuroimaging may be considered in patients suspected to have intracranial space-occupying lesions or other intracranial pathology. Assessment of knowledge and understanding of the disorders Assessment should also include evaluation of knowledge and understanding about the disorder among the patients and their parents/caregivers/family members. Additionally, it is important to evaluate the attitudes and beliefs regarding treatment of both patient and caregivers. It is also important to understand the personal and social resources of the caregivers and the impact of the illness on the caregivers. Develop therapeutic alliance While carrying out the assessment, clinicians should focus on developing a good therapeutic alliance with the child and family, as early as possible, to ensure involvement of the patient and family in the treatment over the period of time. The most important component for development of a good therapeutic alliance involves addressing the concerns of patients and their families and respecting their wishes for treatment. There is also a need on the part of the clinician to be aware of issues such as transference and counter-transference issues, even though these may not be directly addressed in treatment. Ongoing assessment Assessment needs to be considered as an ongoing process and after starting treatment, it is important to continuously assess the response to treatment, adverse effects of medications, medication and treatment adherence, the role of patient's immediate environment on patient's illness, disability assessments, other health-care needs, and ease of access and relationship with the treatment team. Other issues which must be considered include caregiver burden, stigma experienced/perceived by the patient/caregiver, and coping abilities of both patient and the caregivers. Appropriate interventions must be carried out to address the emerging issues during the course of the treatment. FORMULATING A TREATMENT PLAN Formulation of a treatment plan involves deciding about the treatment setting and determining the type of psychological treatment and type of medications to be used [Figure 1]. Both patients and caregivers should be actively consulted while preparing the treatment plan. The treatment plan formulated should be feasible, flexible, and practical to address the needs of the patients and caregivers. Clinicians should continuously work with the patient and the caregivers and keep on re-evaluating the treatment plan and make necessary modifications.Figure 1: Initial evaluation and management plan for depression in children and adolescentsDETERMINE A TREATMENT SETTING Children and adolescents with depression need to be managed in the individualized least restrictive treatment environment, which is safe and effective too. While deciding about the treatment setting following factors should be taken into consideration: clinical severity of symptoms, available support from parents and significant others, motivation for treatment, and ability of family members and significant others to ensure the safety of the patient. Children and adolescents with active suicidal or homicidal ideation, intention, or a plan require close monitoring. Hospitalization is usually indicated when a child or adolescent poses a serious threat of harm to self or others. Other indications for inpatient care are shown in Table 3.Table 3: Indications for admission in children and adolescents with depressionHowever, it is important to remember that, for providing inpatient care, provisions of Mental Health Care Act, 2017 (MHCA, 2017), need to be followed. MONITOR THE STATUS AND SAFETY OF PATIENT Over the course of treatment, the clinical picture of patient may change, with emergence of certain new symptoms and subsidence of the existing symptoms. Accordingly, children and adolescents with depression need to be monitored for the emergence of or change in destructive impulses toward self or others. If anytime during the course of treatment, the risk of harm to self or others is eminent, hospitalization and/or more intensive treatment should be considered. It is also important to reconsider the diagnosis if there are significant changes in a patient's psychiatric status or if there is emergence of new symptoms. PROVIDE PSYCHOEDUCATION TO THE PATIENT AND FAMILY Psychoeducation is an important component of management of depression in children and adolescents. It not only helps the patients and their families, but also helps the clinician. Psychoeducation makes the patient and family members informed partners in the decision-making and also enhances the treatment adherence. Psychoeducation can also help in formulating a treatment plan, decreasing parental self-blame (I'm not a good parent) and blame of the child (He's manipulative, or He's lazy). Psychoeducation can be offered to all family members and/or significant others because the depression (e.g., lack of interest, fatigue, irritability, and isolation) in children and adolescents can affect each of them. Psychoeducation of family members and/or significant others can also help them in identifying their own depressive symptoms and potential need for treatment. Occasionally, family members, peers, and friends take the patient's behaviors personally or otherwise become emotionally overinvolved. This leads to more stress, guilt, or anger for the patient to cope with. Supportive and understanding relationships improve the patient's and family's global functioning and treatment outcome. ENHANCE TREATMENT ADHERENCE The key to the successful treatment of depression is adherence to treatment plans. Hence, the need of regular follow-up and drug compliance needs to be emphasized. Measures which can improve the medication adherence are summarized in Table 4.Table 4: Measures which can improve medication complianceWORK WITH THE PATIENT AND CAREGIVERS TO ADDRESS THE ISSUES OF RELAPSE In view of the fluctuation of symptoms in depression over time, patients and their families need to be informed about the significant risk of relapse. They should be made competent to recognize the early signs and symptoms of a new episode. Families need to be informed that starting treatment during the early phase of the relapse can decrease the likelihood of a full-blown relapse or complication. TREATMENT OPTIONS FOR MANAGEMENT FOR DEPRESSION Treatment options for the management of depression in children and adolescents include psychotherapies, antidepressants, electroconvulsive therapy (ECT), and other somatic treatments such as repetitive transcranial magnetic stimulation (rTMS). Psychotherapeutic interventions Various psychotherapeutic interventions such as cognitive therapy, psychotherapy, art therapy, drama therapy, and family therapy have been used in the management of depression in children and adolescents. These interventions have been evaluated in the form of individual and group interventions. Cognitive-behavioral therapies (CBTs) attempt to address the cognitive distortions in depressed children and adolescents. In CBT, child is the focus of treatment and therapists play an active role in treatment to form a collaborative relationship to solve problems. The therapist guides the child as to how to monitor and keep a record of thoughts and behavior, need for diary-keeping, and importance of homework assignments and treatment consisting of behavioral techniques (activity scheduling) and cognitive strategies (cognitive restructuring). Studies which have evaluated CBT for the management of depression in children suggest that, in short term, CBT is better than no treatment. With respect to the efficacy of CBT among adolescents with depression, there is conflicting evidence to draw any definite conclusion. Some studies suggest that CBT is an efficacious treatment for depressed adolescents and it is better than interventions such as family therapy and supportive counseling. However, some of the studies refute this evidence and suggest that the efficacy of CBT is similar to placebo. Studies which have compared the combination of CBT and medication with medication alone suggest that combination is more effective than the medication alone. A recent meta-analysis which included nine studies evaluating the efficacy of CBT in children and adolescents with depression showed that CBT was better than no treatment, but it was not found to be better than waitlist or placebo. This study further showed that the efficacy of CBT was better in those without comorbidity and without parental involvement. The number of CBT sessions in a treatment course in these studies has varied from 5 to 16 sessions; however, the meta-analysis suggests that the number of sessions does not have a significant influence on the efficacy. Another review of efficacy trials suggests that CBT is more efficacious in adolescents (aged 13–24 years) than in children (aged ≤13 years). In view of the association of depression in children and adolescents with problems in relationship, interpersonal therapies (IPTs) have also been evaluated for the management of depression in children and adolescents. Addressing the interpersonal issues can lead to alleviation of depressive symptoms, irrespective of the personality organization or biological vulnerability of the individual. The main goals of IPT are to identify and treat the depressive symptoms and address the interpersonal issues associated with the onset of depression. A meta-analysis which included data of 538 participants from seven randomized controlled trials (RCTs) showed that, when compared with controlled conditions (placebo, waitlisted, or treatment as usual), IPT had significantly superior efficacy in reducing depressive symptoms and leading to response/remission, for all-cause discontinuation rates and improvement in the quality of life/functional improvement. Another meta-analysis which included ten studies comprising 766 participants which evaluated the efficacy of IPT among adolescents (IPT-A) with depression reported that IPT-A was significantly superior to control or treatment as usual in reducing depressive symptoms among adolescents. In view of the association of depression in children with family pathology, including mental illness and dysfunctional family relationships, many authors suggest the role of family therapy in the management of childhood depression. Use of antidepressants Efficacy of many antidepressants has been evaluated in randomized controlled trials (RCTs) in children and adolescents. Antidepressants which have been evaluated in children and adolescents include imipramine, des-imipramine, clomipramine, nortriptyline, amitriptyline, fluoxetine, paroxetine, escitalopram, sertraline, duloxetine, venlafaxine, nefazodone, and mirtazapine. Results of RCTs of most of these antidepressants came out to be negative. A recent network meta-analysis, which included data on 14 antidepressants from 34 trials involving 5260 participants, concluded that only fluoxetine was significantly better than placebo. This meta-analysis also concluded that fluoxetine was better tolerated than duloxetine and imipramine. Similarly, tolerability of citalopram and paroxetine was significantly better than that of imipramine. A Cochrane review, which included 19 RCTs, which evaluated the efficacy of newer antidepressants in the management of depression in 3335 children and adolescents, concluded that, in general, there is no difference between antidepressants and placebo in terms of efficacy. However, in view of the risk associated with untreated depression, the authors concluded that fluoxetine might be the medication of first choice. Further, the authors concluded that use of antidepressants was associated with an increased risk of suicidal behavior, compared to placebo. The multicentric National Institute of Mental Health-funded study, i.e., Treating Adolescent Depression Study (TADS), which compared the use of fluoxetine alone, CBT alone, or combination of both, concluded that combination of CBT and fluoxetine offered the highest treatment response rates followed by response rate to fluoxetine alone. CBT alone was not found to be efficacious. Response rate to fluoxetine alone was 61% as measured by