What is the preferred treatment for newly-diagnosed depression in teenage girls?

1.

Elsevier ClinicalKey Clinical Overview

Treatment Appropriate treatment depends on symptoms and symptom severity ( Figure 1 ) For patients with mild depressive symptoms: Provide active support to patients and families for 6 to 8 weeks, checking in every 1 to 2 weeks If symptoms resolve, continue routine follow-up and screening If symptoms worsen, consider more active intervention (medication, psychotherapy, and/or referral) For patients with moderate depressive symptoms: Consider referral to mental health specialist or manage within primary care If managing within primary care: initiate medication and/or therapy If partially improved after 6 to 8 weeks: consider adding medication (if not already done), increasing to max dose, adding therapy if not done already, consulting with mental health specialist If not improved after 6 to 8 weeks: reassess diagnosis Same steps as above (see "If partially improved") For patients with severe depressive symptoms or significant comorbidities: Consider consultation by a mental health specialist

Treatment Antidepressants with or without other forms of therapy are an effective treatment for depression in adolescents Fluoxetine is FDA approved for use in children and adolescents aged 8 years and older with MDD Escitalopram is FDA approved for use in adolescents aged 12 years and older with MDD Sertraline is FDA approved for use in children and adolescents with obsessive-compulsive disorder, but has been shown to be safe and effective in the treatment of MDD in children and adolescents Adolescents should have some clinical response at 2 to 3 weeks of therapeutic dose If a response is not noted at this time, increase the dose If a response is seen, continue for 4 to 6 weeks and reassess dose

Treatment Table Title: Table 2. SSRI titration schedule for the treatment of MDD in adolescents. Table Caption: SSRI, selective serotonin reuptake inhibitor., *These medications are contraindicated with concurrent use with monoamine oxidase inhibitors., Data from Cheung AH et al. Guidelines for Adolescent Depression in Primary Care (GLAD-PC). Treatment and ongoing management. Pediatrics 2018;141(3):e20174082. Table Heads: Medication*| Starting dose (every day)| Increments| Effective dose| Maximum dosage

2.

Elsevier ClinicalKey Clinical Overview

Treatment Recommended initial treatment options for patients with moderate to severe major depressive disorder: Recommended initial treatment for patients with mild major depressive disorder is cognitive behavioral therapy Initial treatment with a combination of pharmacotherapy and psychotherapy is recommended for patients with any of the following: The following second generation antidepressants are the first line options for pharmacotherapy: start treatment at low dose and gradually increase to approved maximum dose For patients with an inadequate response to an adequate trial of initial pharmacotherapy (ie, one of the above agents at maximum dose for at least 4 to 6 weeks), options include: Offer repetitive transcranial magnetic stimulation to patients with inadequate response to two or more adequate trials of medication Consider electroconvulsive therapy for patients with any of the following: Relapse prevention Evidence-based psychotherapy (eg, cognitive behavioral therapy) A second-generation antidepressant Combination therapy with psychotherapy and a second generation antidepressant Second-generation antidepressant may be chosen for initial treatment based on considerations such as access to or cost of psychotherapy, history of moderate or severe major depression, or patient preference Consider combination therapy (psychotherapy and pharmacotherapy) when the response to a single therapy is inadequate Severe major depressive disorder (eg, Patient Health Questionnaire-9 score greater than 20) Persistent major depressive disorder (duration longer than two years) Recurrent major depressive disorder (two or more previous episodes) Bupropion Mirtazapine Serotonin-norepinephrine reuptake inhibitors Selective serotonin reuptake inhibitors Trazodone, vilazodone, or vortioxetine Switching to another antidepressant A different second generation antidepressant A second line agent (eg, tricyclic antidepressants, MAOIs, nefazodone)

Treatment Psychotherapy: Structured psychological treatment is foundational in the treatment of all depressive presentations For all severities of depression, the most effective treatment is a combination of psychological interventions and pharmacotherapy Recommended approaches include cognitive behavioral therapy, behavioral activation therapy, interpersonal psychotherapy, problem-solving therapy, nondirective counseling, psychodynamic therapy, acceptance and commitment therapy, mindfulness-based cognitive therapy, and short-term psychodynamic psychotherapy The US Department of Veterans Affairs/Department of Defense, American Psychological Association, and National Institute for Health and Care Excellence guidelines recommend a range of psychotherapies for treatment of depression; however, American College of Physicians guidelines only recommend cognitive behavioral therapy, citing insufficient evidence for other forms May be offered in individual or group format according to patient preference May be used as the initial treatment modality for patients with major depressive disorder, with or without concomitant medication therapy; often adequate as initial therapy early in the course of the disease Cognitive behavioral therapy administered concurrently with medication may increase the rate of patient response Cognitive behavioral therapy administered after medication is withdrawn may impart a protective effect against relapse Music therapy: Music therapy (provided by a music therapist) has been found to decrease depressive symptoms, improve anxiety associated with major depressive disorder, and improve functioning Acupuncture: Small to moderate reduction in the severity of depressive symptoms has been reported Exercise: Exercise has been shown to have significant effect in reducing depressive symptoms in patients with major depressive disorder,

3.

Food and Drug Administration (DailyMed).

Publish date: April 3, 2021.

Clinical Studies 14 CLINICAL STUDIES 14.1 Major Depressive Disorder Adolescents The efficacy of Escitalopram oxalate (escitalopram) as an acute treatment for major depressive disorder in adolescent patients was established in an 8-week, flexible-dose, placebo-controlled study that compared Escitalopram oxalate (escitalopram) 10 mg/day to 20 mg/day to placebo in outpatients 12 to 17 years of age inclusive who met DSM-IV criteria for major depressive disorder. The primary outcome was change from baseline to endpoint in the Children’s Depression Rating Scale - Revised (CDRS-R). In this study, Escitalopram oxalate (escitalopram) showed statistically significant greater mean improvement compared to placebo on the CDRS-R. The efficacy of Escitalopram oxalate (escitalopram) in the acute treatment of major depressive disorder in adolescents was established, in part, on the basis of extrapolation from the 8-week, flexible-dose, placebo-controlled study with racemic citalopram 20 mg/day to 40 mg/day. In this outpatient study in children and adolescents 7 to 17 years of age who met DSM-IV criteria for major depressive disorder, citalopram treatment showed statistically significant greater mean improvement from baseline, compared to placebo, on the CDRS-R; the positive results for this trial largely came from the adolescent subgroup. Two additional flexible-dose, placebo-controlled MDD studies (one Escitalopram oxalate (escitalopram) study in patients ages 7 to 17 and one citalopram study in adolescents) did not demonstrate efficacy. Although maintenance efficacy in adolescent patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of Escitalopram oxalate (escitalopram) pharmacokinetic parameters in adults and adolescent patients.

4.

Food and Drug Administration (DailyMed).

Publish date: May 3, 2024.

Clinical Studies In these studies, fluoxetine produced a significantly higher rate of response and remission as defined, respectively, by a 50% decrease in the HAM-D score and a total endpoint HAM-D score of ≤ 8. Fluoxetine was well tolerated and the rate of treatment discontinuations due to adverse reactions did not differ between fluoxetine (12%) and placebo (9%). A study was conducted involving depressed outpatients who had responded (modified HAMD-17 score of ≤ 7 during each of the last 3 weeks of open-label treatment and absence of MDD by DSM-III-R criteria) by the end of an initial 12-week, open-treatment phase on fluoxetine 20 mg/day. These patients (N = 298) were randomized to continuation on double-blind fluoxetine 20 mg/day or placebo. At 38 weeks (50 weeks total), a statistically significantly lower relapse rate (defined as symptoms sufficient to meet a diagnosis of MDD for 2 weeks or a modified HAMD-17 score of ≥ 14 for 3 weeks) was observed for patients taking fluoxetine compared with those on placebo. Pediatric (children and adolescents)— The efficacy of fluoxetine 20 mg/day in children and adolescents (N = 315 randomized; 170 children ages 8 to < 13, 145 adolescents ages 13 to ≤ 18) was studied in two 8- to 9-week placebo-controlled clinical trials in depressed outpatients whose diagnoses corresponded most closely to the DSM-III-R or DSM-IV category of MDD. In both studies independently, fluoxetine produced a statistically significantly greater mean change on the Childhood Depression Rating Scale-Revised (CDRS-R) total score from baseline to endpoint than did placebo. Subgroup analyses on the CDRS-R total score did not suggest any differential responsiveness on the basis of age or gender.

5.

Zhou X, Teng T, Zhang Y, et al. The Lancet. Psychiatry. 2020;7(7):581-601. doi:10.1016/S2215-0366(20)30137-1.

Publish date: July 3, 2020.

Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as "low" to "very low" in terms of confidence of evidence according to Confidence In Network Meta-Analysis. INTERPRETATION: Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. FUNDING: National Key Research and Development Program of China.