Letters to the Editor

Primary Care Clinicians Can Effectively Treat Depression in Children and Adolescents

 

Am Fam Physician. 2020 Aug 15;102(4):198-199.

Original Article: Depression in Children and Adolescents: Evaluation and Treatment

Issue Date: November 15, 2019

See additional reader comments at: https://www.aafp.org/afp/2019/1115/p609.html

To the Editor: We thank Drs. Selph and McDonagh for recommending an evidence-based approach to the evaluation and management of depression in children and adolescents. In this letter, we propose a nuanced approach to medication selection and referral criteria.

We agree that clinicians should consider fluoxetine (Prozac) or escitalopram (Lexapro) as first-line antidepressants for children and adolescents, optimally in conjunction with cognitive behavior therapy or other evidence-based counseling when feasible. Fluoxetine and escitalopram are indeed the only psychotropics approved by the U.S. Food and Drug Administration for the treatment of unipolar depression in children. However, other selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) may be appropriate first- or second-line agents in specific circumstances. Clinicians should consider co-occurring mental health conditions (e.g., sertraline [Zoloft] for treatment of obsessive-compulsive disorder, which may require a high-dose titration), potential drug-drug interactions, adverse effect profiles based on patient factors, and prior response to or preference for a different antidepressant by the patient or family member (which may predict effectiveness and buy-in).1 Furthermore, older adolescents may benefit from a wider range of psychotropics.2

The authors cite a network meta-analysis supporting the use of fluoxetine as the only medication demonstrating effectiveness, but this study assumes heterogeneity in comparisons; pairwise analyses showed that escitalopram and sertraline are also effective.3 Other studies have demonstrated the effectiveness of fluoxetine, escitalopram, sertraline, and venlafaxine,1,35 including one that demonstrated clinical improvement with SSRIs or SNRIs over placebo.4 Finally, although refractory cases of depression are often excluded from randomized controlled trials, the TORDIA (Treatment of Resistant Depression in Adolescents) trial showed evidence to support the use of venlafaxine for SSRI-resistant depression.5

When caring for youth with depression, clinicians should optimize school, peer, and community resources to foster a patient's sense of connectedness.1 A patient-clinician relationship with appropriate confidentiality protections and parent involvement should facilitate shared decision-making when developing treatment goals.1 If self-harm or suicidality is identified, clinicians should establish and document an individualized plan. Safety-proofing plans should consider, at a minimum, all medication supplies and accessibility of items that may be used as weapons.

The authors recommend referral if fluoxetine and escitalopram are ineffective. We instead propose that, when trained appropriately, primary care clinicians may take an active role in medication management (Table 114) based on experience and patient complexity. We worry that a rigid approach may delay care and cause harm for the most vulnerable youth because of the severe national shortage of child and adolescent mental health specialists.1,6 By applying thoughtfully constructed, evidence-based treatment plans, primary care clinicians can treat youth with depression and fill a critical health services gap.

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TABLE 1.

Selected Medications for the Treatment of Adolescent Mood Disorders

Medication*Starting dosage (mg per day)Dose adjustments† (mg per dose)Therapeutic range (mg)Maximum dosage (mg per day)

Selective serotonin reuptake inhibitors

Citalopram (Celexa)

10

5 to 10

20 to 40

40

Escitalopram (Lexapro)

5 to 10

5

10 to 20

20

Fluoxetine (Prozac)

10

10 to 20

20 to 40

60 to 80

Sertraline (Zoloft)

25 to 50

25 to 50

50 to 200

200

Serotonin-norepinephrine reuptake inhibitors

Duloxetine (Cymbalta)

30

30

30 to 120

120

Venlafaxine XR

37.5

37.5

37.5 to 75

225


Note: Antidepressants include a U.S. Food and Drug Administration boxed warning that all children who are being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of therapy and when increasing or decreasing the dosage.

*—Dosages are based on age, weight, and indications (e.g., co-occurring conditions). These medications should not be used in combination with a monoamine oxidase inhibitor. Escitalopram and citalopram prolong the QTc interval; dosages higher than the maximum should be avoided. Paroxetine (Paxil) is generally not recommended because of its limited effectiveness and adverse effect profile.

†—Typically every two to four weeks after phone or in-person check-ins.

Information from references 14.

TABLE 1.

Selected Medications for the Treatment of Adolescent Mood Disorders

Medication*Starting dosage (mg per day)Dose adjustments† (mg per dose)Therapeutic range (mg)Maximum dosage (mg per day)

Selective serotonin reuptake inhibitors

Citalopram (Celexa)

10

5 to 10

20 to 40

40

Escitalopram (Lexapro)

5 to 10

5

10 to 20

20

Fluoxetine (Prozac)

10

10 to 20

20 to 40

60 to 80

Sertraline (Zoloft)

25 to 50

25 to 50

50 to 200

200

Serotonin-norepinephrine reuptake inhibitors

Duloxetine (Cymbalta)

30

30

30 to 120

120

Venlafaxine XR

37.5

37.5

37.5 to 75

225


Note: Antidepressants include a U.S. Food and Drug Administration boxed warning that all children who are being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of therapy and when increasing or decreasing the dosage.

*—Dosages are based on age, weight, and indications (e.g., co-occurring conditions). These medications should not be used in combination with a monoamine oxidase inhibitor. Escitalopram and citalopram prolong the QTc interval; dosages higher than the maximum should be avoided. Paroxetine (Paxil) is generally not recommended because of its limited effectiveness and adverse effect profile.

†—Typically every two to four weeks after phone or in-person check-ins.

Information from references 14.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army Medical Department or the U.S. Army at large.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Cheung AH, Zuckerbrot RA, Jensen PS, et al. Guidelines for adolescent depression in primary care (GLAD-PC): part II. Treatment and ongoing management. Pediatrics. 2018;141(3):e20174082....

2. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357–1366.

3. Brent DA, Gibbons RD, Wilkinson P, et al. Antidepressants in paediatric depression. BJPsych Bull. 2018;42(1):1–4.

4. Locher C, Koechlin H, Zion SR, et al. Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents. JAMA Psychiatry. 2017;74(10):1011–1020.

5. Brent D, Emslie G, Clarke G, et al. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial [published correction appears in JAMA. 2019;322(17):1718]. JAMA. 2008;299(8):901–913.

6. American Academy of Child and Adolescent Psychiatry. Severe shortage of child and adolescent psychiatrists illustrated in AACAP workforce maps. Accessed December 28, 2019. https://www.aacap.org/App_Themes/AACAP/Docs/press/2018/Press-Release-Workforce-Maps.pdf

In Reply: We agree with Drs. Anvari, Carroll, and Klein in recommending a nuanced approach to depression treatment, taking into account patient comorbidities; drug-drug interactions; adverse effect profiles; prior responses or preference for a particular antidepressant; and the availability of school, peer, and community resources. However, treating children and adolescents with complex psychiatric or medical conditions was beyond the scope of our article. Evidence supports the use of fluoxetine and escitalopram as first-line agents for unipolar depression in children and adolescents without complex medical or psychiatric histories.

We believe in basing recommendations on the best evidence available, and the evidence for sertraline and venlafaxine is not as compelling as that for fluoxetine and escitalopram. Evidence showing that sertraline is more effective than placebo is based on two trials that were reported in one publication as if they were one trial. The analysis broke randomization protocols and ignored potential between-trial variability (heterogeneity), which could have inflated the treatment effect.1 The evidence for venlafaxine includes one trial in children and adolescents with major depressive disorder that did not show a significant treatment effect.2 Evidence from the TORDIA trial supports adding cognitive behavior therapy to medication therapy for treatment-resistant depression.3 However, in the trial, switching to venlafaxine was not better than switching to another SSRI, and treatment with an SSRI resulted in fewer adverse effects than treatment with venlafaxine.3

We agree that some primary care physicians may feel comfortable prescribing antidepressants that are not approved for use in children and adolescents. However, we believe physicians should consult with or refer patients to mental health specialists whenever they are uncomfortable with this. We acknowledge the shortage of child and adolescent mental health specialists and that referral may not be easy (e.g., using telehealth vs. an in-person visit4). But at a minimum, phone consultation with a mental health specialist should occur whenever the primary care physician lacks the comfort and expertise needed to appropriately treat patients when first-line therapies have not been successful.

We agree that safety plans for at-risk children and adolescents should include limiting access to traditional weapons, as well as household items that could be used to inflict harm (e.g., kitchen knives, prescription medications).

Author disclosure: No relevant financial affiliations.

References

show all references

1. Wagner KD, Ambrosini P, Rynn M, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA. 2003;290(8):1033–1041....

2. Locher C, Koechlin H, Zion SR, et al. Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents: a systematic review and meta-analysis. JAMA Psychiatry. 2017;74(10):1011–1020.

3. Brent D, Emslie G, Clarke G, et al. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial [published correction appears in JAMA. 2019;322(17):1718]. JAMA. 2008;299(8):901–913.

4. Totten AM, Hansen RN, Wagner J, et al.; Agency for Healthcare Research and Quality. Telehealth for acute and chronic care consultations. Comparative effectiveness review no. 216. Accessed May 18, 2020. https://effectivehealthcare.ahrq.gov/products/telehealth-acute-chronic/research

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This series is coordinated by Kenny Lin, MD, MPH, Associate Deputy Editor for AFP Online.

 

 

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