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Adolescent depression and antidepressants in the united states

All rights reserved Abstract Depression in children and youth is common, and requires an understanding of its developmental character and associated comorbid conditions. Initial treatment of mild depression involves active supportive measures with a focus on symptom reduction and improved daily function.

For children with more severe symptoms or complicating factors comorbid conditionsreferral to mental health clinicians should be considered. Identifying and managing depression may be challenging in paediatric practices. Young people may not present with classic symptoms; there are different ways of understanding the nature of depression, and there has been considerable concern about the role of antidepressant medications, especially regarding the effectiveness and safety of the most commonly prescribed antidepressants — selective serotonin reuptake inhibitors SSRIs.

Variations in knowledge, medical specialty and community context affect how comfortable paediatricians feel prescribing SSRIs for their patients.

Based on an overview of key review articles and practice guidelines, the present article discusses recent evidence regarding the use of SSRIs to treat depression in children and youth, and risks regarding safety, as well as presents practice touch points to guide management.

Readers seeking a comprehensive account of the prevention, assessment and management of depression in children and youth may refer to more detailed sources 2 — 4. The use of SSRIs for other childhood mental health conditions, such as anxiety and obsessive compulsive disorder, is beyond the scope of the present article. Second, SSRI antidepressants are frequently prescribed, but with the exception of fluoxetine, sertraline and citalopram 5evidence supporting their effectiveness in this setting is limited.

Third, given concerns about the association between SSRIs and suicide risk with a causal link not yet establishedand recent evidence of recurrence or relapse following medication and short-course psychological therapies 6careful, close and long-term follow-up is essential.

MDD in childhood Depression typically encompasses both MDD and dysthymic disorder, and impairs function in one or more major areas of daily living, and family and peer relations.

Such symptoms may include insomnia and weight loss, attentional difficulties, irritability, aggression, and social or academic impairment. Early onset in adolescence appears to predict a more chronic and recurrent course than depression that starts in adulthood 89. In childhood, boys experience MDD at the same rate as girls, while in adolescence, females are twice as likely to be depressed 10.

Questions regarding SSRI effectiveness The evidence for antidepressant efficacy among children and teenagers treated for depression is limited and somewhat inconsistent 51718. To date, the body of evidence for the efficacy of fluoxetine is more consistent than for other SSRIs 51720although there is some evidence for the efficacy of sertraline and citalopram 18.

Available evidence suggesting that one SSRI is better than another may be largely attributable to study methodological considerations for example, how patients are selected, endpoints used, etcas well as wide variations in placebo responses observed across trials 18.

A failure to account for concurrent stressful life events parental support, poor school functions and chronic illnessto stratify the data according to age ie, grouping younger and older children together into one cohort and to account for the high rates of concurrent maternal depression 11 are other methodological inconsistencies that potentially influence the ability to detect antidepressant efficacy.

For years, fluoxetine was the only SSRI approved for the treatment of depression among children and youth in the US, although recently escitalopram has been approved.

Consistent data reporting on the effectiveness of other newer generation antidepressants remain lacking 11. Importantly, no SSRI has consistently demonstrated positive results for depressive disorders in prepubertal children 5. Questions regarding SSRI safety and suicide risk With increasing rates of prescriptions and concerns about safety and efficacy of antidepressants, the past decade has been an unsettling time for the management of depression in children and adolescents 13.

The possibility of increased suicide risk or suicidality has been a particular concern, leading to warnings placed by regulatory agencies 21. In the early 2000s, reports appeared associating SSRIs with a higher risk of suicidal behaviour in children and adolescent depression and antidepressants in the united states 22.

Shortly after the 2003 US Food and Drug Administration approval of fluoxetine for MDD in children seven to 17 years of age, a public warning followed in 2004 highlighting an increased risk for suicidal ideation and behaviour in children and youth treated with these antidepressants.

Higher rates adolescent depression and antidepressants in the united states SSRI prescriptions are associated with lower rates of suicide in children, although because this is correlational evidence, the true nature of the relationship remains unclear 25.

To date, the best evidence shows that SSRI treatment decreases suicidal ideation and attempts 182627 because findings do not support a strong relationship between suicide risk in youth and SSRI treatment 27. Troublesome psychiatric or behavioural side effects associated with SSRIs may resemble depression itself and require close ongoing monitoring 5. Decisions regarding the management of MDD must be made by weighing the possible risks of SSRI treatment against the risks associated with the disorder itself.

The consequences of untreated disorders can be devastating to children and parents alike. Nontreatment is never an option, and untreated or undertreated MDD may adversely affect the development of emotional, cognitive, academic and social achievements, and interfere with family relationships 8.

Suicide is the adolescent depression and antidepressants in the united states leading cause of death in five- to 14-year-old children, and the third leading cause of death in the 15- to 24-year-old age group 18.

Evaluate for depression in children and youth who present with mood disturbances, emotional problems Assessments guided by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition criteria using standardized tools including direct interviews with patients, families, caregivers, assessment of functional impairment home, school and peer settings and other comorbid conditions 2.

Outpatient treatment of child and adolescent depression in the United States.

Confirm diagnosis and severity of the condition The diagnostic criteria should be clearly met, and functional impairment should be clearly documented. Check for other potential causes of the depressive presentation eg, substance abuse, prodromal psychotic state 3. Suicidal risk at baseline? While measuring symptoms of depression at the initial assessment, special attention to suicidality needs to be documented 5.

Open discussion Provide comprehensive information about the illness and various treatment options to the patient and family. Appropriate literature should be available in your office and you should have a list of reputable websites to which you can direct their attention.

Where to start therapy After an initial diagnosis for mild depression, start with a period of active support and monitoring symptoms — follow-up visit in seven to 10 days 7. When to start an SSRI? Medications should be reserved for the treatment of moderate to severe conditions 8. Where to get started with an SSRI: Do no harm Do a proper risk-benefit relationship analysis of the situation. Acknowledge risks for antidepressant Check for signs and symptoms that may imply an increased risk of adverse effects ie, risk for switch to mania.

Review what other drugs are currently being used and the risk for adverse drug effects Drug-drug interactions? Potential for therapeutic failure or toxicity? Consider role of hepatic cytochrome 450 factors in risks for side effects or therapeutic failure. History of previous adverse reactions to psychotropic drugs, and concurrent use of psychotropic medications that might increase risk for drug-drug interactions 11. Starting an antidepressant Provide the patient and family with a detailed account of the possible adverse effects both behavioural and somaticand the expected timelines to improvement.

Document your discussion 12. Since starting an antidepressant is rarely emergent and the time it takes to see a response is several weeks, you only need to increase the dose slowly eg, once a week until the expected minimally effective dose is reached. Where possible, wait the required six to eight weeks to determine efficacy 13. Tracking goals and outcomes Goals should include improved functional status school, home and peers and lessening of depressive symptoms. See the patient weekly where possible for the first few weeks and allow for telephone follow-up whenever the dose is changed.

Always ask about and document any adverse effects use a monitoring form. Monitoring on a monthly basis should extend for six to 12 months after the resolution of symptoms and, with a recurrence of symptoms, monitoring should be extended to two years 15.

If no improvement in six to eight weeks, diagnosis and initial treatment should be reassessed. For children or youth with persisting moderate or severe depression ie, therapeutic failure or complicating factors substance abuse or psychosis, suicidal or homicidal ideation, or new or worsening comorbid conditionsconsultation with a psychiatrist is needed 16.

Taking advantage of the placebo effect Take advantage of the placebo response found to be high in most adolescent depression trials. That is, invoke a similar approach to patient care as in studies, including frequent face-to-face contact early in the course of therapy, the development of a trusting and supportive relationship, efforts to measure response objectively and subjectively, and careful elicitation of side effects, overall tolerance, ongoing concerns and satisfaction with treatment 17.

Pharmacotherapeutic failure Consider what else is going on: Consider drug-drug interactions, pharmacogenetic or dietary influences ie, grapefruit 18. Where are you in your community — do you have a shared care plan? Shared care between paediatricians, family physicians and psychiatrics should be sought when possible.

Appropriate roles and responsibilities regarding the coordination of care should be communicated on a regular basis Adapted from references 3527 and 30 Current expert opinion suggests that nonpharmacological approaches are essential first-line treatments 52829.

A key part of any initial assessment is consideration of individual developmental differences and emerging capacities for self-regulation that underlie psychological and physiological development inherent to childhood and adolescence. Both genetic and nongenetic factors have an influence, thus highlighting the importance of a family history for MDD 31. However, even in high-risk adoption and twin settings, MDD is a familial disorder that is critically interwoven with environmental and early life experiential factors 32.

Use of depression screening instruments may be helpful in establishing a diagnosis; however, these should not take the place of sound clinical judgment based on direct interview. Combined self-report and parent report using depression checklists and clinical interviews may increase the awareness of underlying family, peer and comorbid conditions.

Where symptoms are mild or the diagnosis is unclear, an initial period of careful observation and active supportive therapy is warranted. This should include a focus on management of comorbid anxiety, functional needs, availability of self-help material and addressing psychoeducational needs, as well as establishing regular sleep, nutrition, coping patterns, family interventions and exercise including a course of psychotherapy 30 or cognitive behavioural therapy 262834.

Enlisting school-based supports should also help set realistic academic, social and activity expectations. Where symptoms are severe or persist with comorbid disorders, the use of SSRIs may be indicated 30. Best practice 2352730 suggests the deployment of combined treatment with both medication and psychotherapy, with careful monitoring of benefits and safety risks 35.

The decision to initiate SSRI use should be made within a broad and comprehensive therapeutic context of continuing to promote social, emotional and physical health that supports self-esteem, improves the quality of family and peer relationships, and healthy lifestyles, and identifies the potential onset of worsening of suicidality 11. As covered above, the best evidence supports the use of fluoxetine for depression 1836although this drug has not been approved for use in Canada in children younger than 18 years of age 527.

SSRI treatment needs to begin with a realistic discussion of the expectations child, parents and clinicians about the risks and potential benefits, identification of target symptoms and adverse effects behavioural and emotional.

Importantly, because the benefits of SSRI treatment may be delayed and placebo response rates may be high, the initiation of antidepressant therapy could be delayed beyond the first visit. Following the initial consultation, a follow-up appointment for the re-evaluation of symptoms, level of self-harm and reconsideration of the diagnosis within seven to 10 days is essential. Both patients and caregivers need to be properly informed about the potential for medication benefits and risks, with close monitoring of suicide risk and efforts to ensure there is no acute cessation of SSRI treatment 5.

Understanding key features of SSRI pharmacology is essential. Because SSRIs primarily act by blocking the serotonin transporter, consequently increasing extracellular serotonin levels, they may lead to pathological increases in serotonin, and potential serotonin syndrome, when used in combination with other serotonergic medications antidepressants, opioids and central nervous system stimulants.

SSRI effects may be mediated by genetic factors that influence the availability of serotonin at the presynaptic membrane ie, serotonin transporter polymorphisms that regulate the levels of the transporter proteinand the presence of concurrent adolescent depression and antidepressants in the united states drugs, leading to adverse side effects and hepatic CYP450-dependent metabolism 37.

Ongoing monitoring is essential for the emergence of adverse events, suicidality and behavioural changes, particularly during the initial few months of treatment. This should include seeing the patient weekly for the first few weeks, and subsequently allowing for telephone follow-up when doses change. Systematic and ongoing documentation of findings is recommended.

Monthly monitoring should extend from six to 12 months after the resolution of symptoms; with recurrence of symptoms, patients should be monitored for a two-year period. If no improvement is observed in the first six to eight weeks, diagnosis and initial treatment should be reassessed and the low starting dose should be optimized ie, fluoxetine dose increased to 30 mg or 40 mg if tolerated.

However, even when a systematic comprehensive approach has been pursued, therapy can still fail; recurrences are not infrequent 6. Consultation with a psychiatrist should be sought where moderate or severe depression persists ie, therapeutic failure or coexisting substance abuse, psychosis, suicidal or homicidal ideation, or worsening comorbid conditions emerge. Ideally, management of child and youth depression requires a shared care plan between paediatricians, family physicians, psychiatrists, and associated health and education professionals.

The need for collaborative health care has been recently highlighted by adolescent depression and antidepressants in the united states study of paediatricians in British Columbia who overwhelmingly reported that children with mental health problems need comprehensive team approaches with timely access to community resources 38.

Emerging evidence suggests that shared care models may be beneficial for the management of depression in children 30. Such community-based teams can promote professional education, strengthening mental health services for the child, family and professionals. The lifelong implications of early poor mental health 1 warrant the use of a chronic illness perspective to promote improved outcomes well into adulthood. Although many uncertainties persist in approaching and managing childhood depression, paediatricians can play a critical role.