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Abstract

I recently had an adolescent patient who

presented with a chief complaint of depres-

sion. He had classic symptoms of difficulty

sleeping, dysthymia, and anhedonia (loss

of interest in things that used to bring him

joy). He was a very smart and self-aware

17-year-old, and was able to describe his

symptoms easily. There were no concerns

for manic episodes or psychosis, and he

met diagnostic criteria for unipolar major

depressive disorder. He denied suicidal

ideation, and was already seeing a thera-

pist weekly for the last several months. He

had a strong family history of depression,

with his father, aunts, and grandmother

who also carried a diagnosis of depres-

sion. He presented with the support of his

mother, asking about next steps, and spe-

cifically, pharmacotherapy. This patient is a

perfect example of an adolescent who is

a good candidate for initiation of antide-

pressant medication. Primary care pediatri-

cians should feel comfortable with first-line agents for major depressive disorder in cer-

tain adolescents with depression, but many

feel hesitant and rely on child and adoles-

cent psychiatry colleagues for prescriptions.

[Pediatr Ann. 2015;44(11):466-468,470.]

This article is aimed at giving primary care pediatricians prac-tical tips for the initiation and

management of antidepressants, as well as advice on when to ask specialists for help. This article does not discuss the screening or diagnosis of pediatric

depression, but it is worth saying that pediatric and adolescent depression is a common, treatable problem. It is es-timated that 3% to 8% of adolescents suffer from depression.1,2 In many in-stances, patients have their first major depressive episode in the adolescent period between ages 15 and 24 years (Figure 1). This diagnosis is relatively common, and for certain patients, ini-tiation of antidepressant medication by a primary care pediatrician can be an important step in their recovery.

Treating Teen Depression in Primary CareSabrina Santiago, MD

Sabrina Santiago, MD, is a Primary Care Pe-

diatrician, University of California San Francisco,

Benioff Children’s Hospital; and an Assistant Pro-

fessor of Pediatrics, Department of Pediatrics,

University of California San Francisco.

Address correspondence to Sabrina Santiago,

MD, via email: sabrina.santiago@ucsf.edu.

Disclosure: The author has no relevant finan-

cial relationships to disclose.

doi: 10.3928/00904481-20151112-03

Figure 1. A teenage patient with depression talking with a physician.

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Although this article focuses pri-marily on pharmacotherapy for de-pression, it is important to say that psychotherapy and psychoeducation, regular exercise, healthy diet, and good sleep hygiene, as well as family therapy and support organizations can be paramount in helping an adolescent conquer depression. Lastly, it is im-portant to approach adolescent depres-sion in an integrative fashion, seeking the help of therapists, social workers, and/or case managers when possible. This is especially important, because many patients have significant social stressors that may not be addressed by medication, including bullying, abuse, or family discord. Combina-tion therapy with psychotherapy and pharmacotherapy has been shown in some studies to be superior to phar-macotherapy alone, particularly in the first few months of treatment, with im-provements in function as well as de-crease in suicidal ideation.3,4

FIRST-LINE AGENTSThe first-line agents for major de-

pressive disorder in adolescents are the selective serotonin reuptake inhibitors (SSRIs). There is consistent evidence for several SSRI medications, and fewer side effects than older agents such as tricyclic antidepressants. The most well-studied agent is fluoxetine. Important issues to consider prior to starting medications are patient or family preference, known allergy to fluoxetine, and drug-drug interactions. Additionally, SSRI medications may inhibit hepatic cytochrome P450 en-zymes that metabolize other medica-tions. Medication interactions include benzodiazepines, warfarin, clozapine, and monoamine oxidase inhibitors among others. Thankfully, many pe-diatric patients are otherwise healthy, and if they are taking other medica-

tions, many resources exist for provid-ers to determine the risk of drug-drug interactions.

SECOND-LINE AGENTSThe evidence for fluoxetine is

strong, with some studies showing that 70% of pediatric depressive episodes remit with initiation of fluoxetine.5 However, for those 30% of patients that have continued symptoms, escita-lopram, citalopram, and sertraline are also SSRIs that are reasonable options. Venlafaxine is also a reasonably well-studied alternative.6,7 It is interesting to note that some SSRI medications, such as paroxetine, have not been shown to be effective in pediatric de-pression, despite being an SSRI.8

If several options above have failed to improve the patient’s depression, seeking the help of a child and adoles-cent psychiatrist is a good next step. Other agents, including buproprion or duloxetine, may be tried but have less evidence in pediatrics, and buproprion has an unfortunate side effect of ap-petite suppression that may be detri-mental in growing adolescents. Tricy-clic antidepressants are rarely used for treatment of depression in adolescents because of limited data showing effi-cacy and more severe side effects in-cluding autonomic symptoms.

FOLLOW UP AND DOSE ADJUSTMENT

Once you have decided on a medi-cation, start at a low dose and titrate upward. Therapeutic effects can take 1 to 8 weeks to materialize; therefore, many physicians recommend waiting 2 to 4 weeks before increasing the dose or switching to a different medication. Some psychiatrists recommend even faster titration, every 1 to 2 weeks. If switching between SSRIs, the clini-cian should taper the patient off slow-

ly, with 1 to 2 weeks between dose ad-justments. The reason for a relatively slow taper is because SSRIs have a rel-atively long half-life. See Table 1 for dose adjustments for common SSRI medications.

Once started on SSRI medication, checking in monthly is a good start to screen for any side effects and to check efficacy of the current dose. Common side effects of SSRIs include gastro-intestinal symptoms (loose stools or constipation, change in appetite, nau-sea, belly pain), dry mouth, sweating, sleep disturbance, headache, rash, and sexual dysfunction. Additionally, SS-RIs can be activating, causing patient symptoms of agitation and restless-ness. “Disinhibition” may also occur, with risk-taking behaviors or increased impulsivity. Fluoxetine seems to be slightly more activating than other SSRI medications. This disinhibition may be related to concerns about in-creased suicide risk with initiation of SSRIs, and suicidal ideation must be assessed at every follow-up visit.

Some side effects may be transient, so if they are mild and tolerable, phy-sicians can continue medication for 2 to 5 days to see if the side effects resolve. More serious side effects are rare, but include serotonin syndrome, hypomania, akathesia (severe restless-ness), and discontinuation syndrome, which may occur with abrupt cessation of antidepressants.

In addition to screening for side ef-fects after initiation of medications, pediatricians should assess efficacy to determine next steps. A commonly used rating scale for pediatric de-pression is the Patient Health Ques-tionnaire.9 This rating scale can be administered easily in a primary care office. Once stabilized, monthly check-ins with the pediatrician are reasonable as well as symptom check

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lists periodically (every 3 months is a reasonable regimen).

Short-term prognosis for children and adolescents with unipolar depres-sion is good—approximately 60% respond to initial treatment.10 Most patients need to be on antidepres-sant medications for 6 to 12 months. However, some patients with more severe depression may need longer than 12 months of medication. It is important to note that remission of-

ten occurs with abrupt cessation of antidepressant medications.

BLACK BOX WARNING FOR SSRI MEDICATIONS: INCREASED SUICIDALITY

Pediatricians often hesitate to pre-scribe antidepressants because of the black box warning for increased sui-cidality with SSRI medications. In 2004, the US Food and Drug Admin-istration (FDA) reviewed 24 clini-

cal trials including 4,400 youth with depression, anxiety, or obsessive-compulsive disorder. They analyzed suicidal thoughts in short-term treat-ment with SSRIs (4-16 weeks). Al-though no suicides occurred in these patients, the FDA found that 4% of patients treated with SSRIs had in-creases in suicidal thoughts, com-pared to 2% of patients treated with placebo.

Suicidal ideation is certainly a symptom that needs to be assessed at every visit, and because it is a symptom, rates of prescribing SSRIs have reduced substantially since the black box warning was instituted. At the same time, there has also been an increase in completed suicides in youth.5 There is no proven causal re-lationship, but many feel that antide-pressants (Figure 2) can be effective in preventing suicide in children and adolescents.

WHEN TO GET HELP FROM A CHILD PSYCHIATRISTThe patient described at the begin-ning of the article is an ideal candi-date for treatment of depression by a primary care pediatrician. The patient was amenable to therapy, had a good network of support from friends and family, was healthy otherwise, and without comorbid substance abuse, eating disorder, or other health prob-lems, and was not suicidal. Patients who are actively suicidal may need inpatient treatment and consulta-tion with a psychiatrist. Other issues that may need consultation include:

1. High risk for suicidal behavior and/or history of suicide attempts;2. Presence of substance abuse;3. Presence of eating disorder;4. Presence of manic or psychotic

symptoms;Figure 2. A young patient receiving medication from her physician.

continued on page 470

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TABLE 1.

Dose Adjustments for Common SSRIs

SSRIStarting Dose

(mg/day)

Incremental Increase (mg/day)

Every 2-4 Weeks

Incremental Taper (mg/day) Every 1-2 Weeks

Effective Dosage Range (mg/day)

Citalopram 10 5-10 10 10-40

Escitalopram 5 5 5 10-20

Fluoxetine 10 10 10 10-60a

Sertraline 25 25 25 25-200

Abbreviation: SSRIs, selective serotonin reuptake inhibitors. aFor fluoxetine the dose range varies based on diagnosis—10 to 40 mg for depression and 10 to 60 mg for anxiety.

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5. No improvement after 6 to 8 weeks of treatment;6. Recurrent/chronic depression lasting more than 2 years;7. Severe functional impair-ment;8. Psychiatric comorbidities;9. Complicated psychosocial factors, ie, dysfunctional family dynamics; and10. Inadequate response to ini-tial therapy or clinician discomfort in managing antidepressant medi-cations.

ALTERNATIVE THERAPIES FOR MAJOR DEPRESSIVE DISORDER

Patients may suggest use of St. John’s Wort or fish oil to treat depres-sion. However, for both of these alter-native therapies, there are limited data for their efficacy in both pediatric pa-tients and adult patients. Additionally,

St. John’s Wort can have drug-drug interactions and, in particular, can in-teract with oral contraceptive pills.

CONCLUDING REMARKSPediatric depression is a common

problem and primary care pediatri-cians can feel comfortable initiating antidepressant medications in certain low-risk patients. For the patient with clear unipolar depression, low suicide risk, and no improvement with psy-chotherapy alone, an antidepressant prescription from a primary care pedi-atrician is a reasonable next step in the process toward recovery. See Table 2 for a few take-home points.

REFERENCES 1. Guideline for Adolescent Depression in

Primary Care (GLAD-PC) Toolkit. http://www.thereachinstitute.org/images/GLAD-PCToolkit_V2_2010.pdf. Accessed Octo-ber 15, 2015.

2. Zuckerbrodt RA, Cheung AH, Jensen PS,

et al; GLAD-PC Steering Group. Guide-lines for adolescent depression in primary care (GLAD-PC): I. Identification, assess-ment, and initial management. Pediatrics. 2007;120(5):e1299-1312.

3. Dubicka B, Elvins R, Roberts C, Chick G, Wilkinson P, Goodyer IM. Combine treat-ment with cognitive-behavioural therapy in adolescent depression meta-analysis. Br J Psychiatry. 2010;197(6):433-440.

4. March J, Silva S, Petrycki S, et al. Fluox-etine, cognitive behavioral therapy and their combination for adolescents with de-pression: Treatment for Adolescents With Depression Study (TADS) randomized con-trolled trial. JAMA. 2004;297:807-820.

5. Gibbons RD, Hur K, Bhaumik DK, Mann JJ. The relationship between antidepres-sant prescription rates and rate of early adolescent suicide. Am J Psychiatry. 2006;163:1898-1904.

6. Brent D, Emslie G, Clarke G, et al. Switch-ing to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depres-sion: the TORDIA randomized controlled trial. JAMA. 2008;299(8):901-913.

7. Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled ran-domized trials of fluoxetine and venlafax-ine. Arch Gen Psychiatry. 2012;69(6):572-579.

8. Hetrick SE, McKenzie JE, Cox GR, Sim-mons MB, Merry SN. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Data-base Syst Rev. 2012;11:CD004851.

9. Richardson LP, McCauley E, Grossman DC, et al. Evaluation of the Patient Health Questionnaire (PHQ-9) for detecting major depression among adolescents. Pediatrics. 2010;126(6):1117-1123.

10. Birmaher B, Brent D; AACAP Work Group on Quality Issues, et al. Practice parameter for the assessment and treatment of chil-dren and adolescents with depressive disor-ders. J Am Acad Child Adolesc Psychiatry. 2007;46(11):1503-1526.

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TABLE 2.

Take-Home Points• In general, SSRIs are the first-line treatment for pediatric unipolar depression. Fluoxetine in

particular has the most evidence for efficacy

• Frequent follow-up visits are necessary to assess for improvement in mood and side effects

• There is a black box warning for increased suicidal risk for many antidepressant medications,

and so suicidal ideation must be assessed at every visit

• SSRI medications need time to take effect, and must be slowly weaned. Abrupt cessation of

antidepressant medications may cause recurrence of depressive symptoms

• Besides antidepressant medication, psychotherapy and support from case managers and

social workers can play an important role in sustaining patients through depression

Abbreviation: SSRIs, selective serotonin reuptake inhibitors.