Narrative review
Antidepressant use in children and adolescents:
Practice touch points to guide paediatricians
Tim F Oberlander MD FRCPC1,2, Anton R Miller MB ChB FRCPC1,2
TF Oberlander, AR Miller. Antidepressant use in children and
adolescents: Practice touch points to guide paediatricians.
Paediatr Child Health 2011;16(9):549-553.
Depression in children and youth is common, and requires an under-
standing of its developmental character and associated comorbid con-
ditions. Initial treatment of mild depression involves active supportive
measures with a focus on symptom reduction and improved daily func-
tion. Where pharmacotherapy is warranted, evidence supports the use
of selective serotonin reuptake inhibitor (SSRI) antidepressants, par-
ticularly fluoxetine, to manage moderate/severe depression. SSRI
treatment should include a comprehensive management plan in the
context of interdisciplinary care, an understanding of its pharmacology
and clearly articulated goals for symptom reduction, functional status
tracking (school, home and peers) and monitoring for the emergence
of suicidal ideation/behaviour. For children with more severe symp-
toms or complicating factors (comorbid conditions), referral to mental
health clinicians should be considered. Use of an SSRI should be asso-
ciated with family/patient education about medication effects, specific
social and health goals that promote self-esteem, improved function
and close monitoring for adverse effects.
Key Words: Depression in children and youth; Management of depression
in a paediatric community setting; Selective serotonin reuptake inhibitor
(SSRI) antidepressants
D epressive disorders affect one in five children before 18 years
of age, and may have a significant impact on psychosocial
function and academic achievement, as well as increased risks for
suicide and health across the child’s lifespan (1). 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 sero-
tonin reuptake inhibitors (SSRIs). Variations in knowledge, med-
ical specialty and community context affect how comfortable
paediatricians feel prescribing SSRIs for their patients. Rather
than developing a ‘one size fits all’ approach, decision-making
principles are needed that optimize the benefits of SSRI therapy
and reduce the risks for adverse effects. Based on an overview of
key review articles and practice guidelines, the present article dis-
cusses recent evidence regarding the use of SSRIs to treat depres-
sion in children and youth, and risks regarding safety, as well as
presents practice touch points to guide management. We refer to
SSRIs and nonselective serotonergic inhibitors collectively under
the rubric of SSRIs. Readers seeking a comprehensive account of
the prevention, assessment and management of depression in chil-
dren and youth may refer to more detailed sources (2-4).The use of
1Divisionof Developmental Pediatrics, Department of Pediatrics, University of British Columbia; 2Child and Family Research Institute, University of British
Columbia, Vancouver, British Columbia
Correspondence: Dr Tim F Oberlander, Child and Family Research Institute, Room F605, 4480 Oak Street, Vancouver, British Columbia V6H 3V4.
Telephone 604-453-8306, fax 604-875-2384, e-mail toberlander@cw.bc.ca
Accepted for publication July 28, 2011
Paediatr Child Health Vol 16 No 9 November 2011
L’utilisation des antidépresseurs chez les enfants
et les adolescents : des points de pratique pour
orienter les médecins
La dépression est courante chez les enfants et les adolescents. Il faut en
comprendre la nature développementale et les pathologies comorbides.
Le traitement initial d’une dépression bénigne comporte des mesures de
soutien actives axées sur la diminution des symptômes et l’amélioration
du fonctionnement quotidien. Lorsqu’une pharmacothérapie s’impose,
les données probantes appuient l’utilisation d’antidépresseurs sous forme
d’inhibiteurs spécifiques du recaptage de la sérotonine (ISRS),
notamment la fluoxétine, pour prendre en charge la dépression modérée
à profonde. Le traitement aux ISRS doit s’associer à un plan de prise en
charge détaillé dans un contexte de soins interdisciplinaires, à la
compréhension de sa pharmacologie ainsi qu’à des objectifs bien établis
de réduction des symptômes, de suivi de l’état fonctionnel (à l’école, à la
maison et avec les camarades) et de suivi de l’émergence d’idéations ou
de comportements suicidaires. Chez les enfants qui présentent des
symptômes plus graves ou des facteurs de complication (pathologies
comorbides), il faut envisager un aiguillage vers un clinicien en santé
mentale. Avant de prescrire un ISRS, il faut informer la famille et le
patient des effets du médicament, des objectifs sociaux et sanitaires qui
favorisent l’estime de soi, de l’amélioration du fonctionnement et du
suivi étroit des effets indésirables.
SSRIs for other childhood mental health conditions, such as anx-
iety and obsessive compulsive disorder, is beyond the scope of the
present article.
In considering the use of SSRIs to manage major depressive
disorders (MDD) in children, three key features need to be con-
sidered. First, MDD in children and adolescents is a common dis-
order that has implications for mental and physical well being
across the child’s lifespan; as such, it may be considered a child-
hood developmental disorder. Second, SSRI antidepressants are
frequently prescribed, but with the exception of fluoxetine, ser-
traline and citalopram (5), evidence supporting their effectiveness
in this setting is limited. Third, given concerns about the associa-
tion between SSRIs and suicide risk (with a causal link not yet
established), and recent evidence of recurrence or relapse follow-
ing medication and short-course psychological therapies (6), care-
ful, close and long-term follow-up is essential.
MDD in childhood
Depression typically encompasses both MDD and dysthymic disor-
der, and impairs function in one or more major areas of daily liv-
ing, and family and peer relations. While altered mood may be a
leading symptom, depression may present as a range of emotional
disturbances; clinicians need to be sensitive to the changing or
‘evanescent’ character of childhood emotional disturbances that
©2011 Pulsus Group Inc. All rights reserved 549
Oberlander and Miller
often contribute to diagnostic uncertainty. Such symptoms may
include insomnia and weight loss, attentional difficulties, irritabil-
ity, aggression, and social or academic impairment.
MDD affects 2% of children and 8% of adolescents, and
increases the risk of substance abuse, attempted and completed
suicide, and depression later in adulthood (7). Early onset in ado-
lescence appears to predict a more chronic and recurrent course
than depression that starts in adulthood (8,9). Approximately
50% of children and adolescents remain clinically depressed at
12 months, and 20% to 40% at 24 months (8), with many
developing episodes into adult life (1). In childhood, boys experi-
ence MDD at the same rate as girls, while in adolescence, females
are twice as likely to be depressed (10). Moreover, children of
depressed parents carry a 15% to 45% lifetime risk for MDD; first-
degree relatives of depressed children and adolescents have an
MDD prevalence rate of 20% to 46% (11), highlighting long-term
implications of childhood mental illness across the lifespan (1).
Comorbid conditions (anxiety, aggressive disorders and substance
abuse) are found in 40% to 70% of children and youth with
MDD.
Trends in SSRI prescription use
The move from tricyclic antidepressants to SSRIs in the 1990s was
accompanied by substantial increased use of SSRIs (12), as well as
critical questions about their safety and effectiveness (2,13).
Antidepressant prescriptions to children increased threefold to
10-fold in the United States (US) from 1987 to 1996 (14); in
Canada, prescription prevalence among children increased by
75% to 80% between 1997 and 2003 (12). This was followed by a
sharp decline in antidepressant use in 2003, most likely reflecting
a response to Health Canada’s warnings related to reports of sui-
cidal ideation/attempts associated with paroxetine use (12). In a
2000 US study, an estimated 25% of paediatricians and more than
40% of family physicians prescribed SSRIs for children younger
than 18 years of age (15). In 2003, it was estimated that just under
2% of the Canadian paediatric population were prescribed anti-
depressants (16).
Questions regarding SSRI effectiveness
The evidence for antidepressant efficacy among children and
teenagers treated for depression is limited and somewhat inconsis-
tent (5,17,18). A high rate of placebo response rates in children
and youth (40% to 60%) (8), and substantial research methodo-
logical issues, have together contributed to the uncertainty
regarding how SSRIs can and should be used for the management
of depression in children and youth (19). To date, the body of
evidence for the efficacy of fluoxetine is more consistent than for
other SSRIs (5,17,20), although there is some evidence for the
efficacy of sertraline and citalopram (18). Available evidence sug-
gesting that one SSRI is better than another may be largely attrib-
utable to study methodological considerations (for example, how
patients are selected, endpoints used, etc), as well as wide varia-
tions in placebo responses observed across trials (18). A failure to
account for concurrent stressful life events (parental support, poor
school functions and chronic illness), to stratify the data accord-
ing 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 inconsisten-
cies 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. To date, no
SSRIs have been approved in Canada for persons younger than
18 years of age. Consistent data reporting on the effectiveness of
550
other newer generation antidepressants remain lacking (11).
Although fluoxetine (with or without short-course psychother-
apy) is associated with recovery in the majority of treated adoles-
cents, follow-up studies show that almost 50% may experience
depression recurrence within the first five years (6), illustrating
the complexities and challenges of managing depression among
youth. Importantly, no SSRI has consistently demonstrated posi-
tive 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 unset-
tling time for the management of depression in children and ado-
lescents (13). The possibility of increased suicide risk or suicidality
has been a particular concern, leading to warnings placed by regu-
latory agencies (21).
In the early 2000s, reports appeared associating SSRIs with a
higher risk of suicidal behaviour in children and adolescents (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. The 2004 report cited a significant increased risk of
“possible suicidal ideation and suicidal behavior” by 80%, and of
agitation/hostility and aggression by 130% (23). While this was
confirmed by Hammad et al’s (23) meta-analysis, other reports have
been inconclusive (15), and yet others have failed to identify an
increased risk (24). Higher rates of SSRI prescriptions are associated
with lower rates of suicide in children, although because this is cor-
relational evidence, the true nature of the relationship remains
unclear (25). To date, the best evidence shows that SSRI treatment
decreases suicidal ideation and attempts (18,26,27) 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, cogni-
tive, academic and social achievements, and interfere with family
relationships (8). Suicide is the most significant and devastating
outcome – with approximately 60% reporting having considered
suicide and 30% actually attempting suicide (7). Suicide is the
sixth 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). However, ‘treatment’ for depressive disorders is not
necessarily synonymous with medical treatment, as discussed
below.
Establishing decision-making practice points to guide use of
SSRIs (Table 1)
Current expert opinion suggests that nonpharmacological
approaches are essential first-line treatments (5,28,29). The initia-
tion of antidepressants in childhood must be based on a thorough
understanding of the child, family and social/school context
(3,30). 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. This should
include risks for substance abuse, presence of stressful life events,
possible effects of prenatal substance/alcohol exposure, physical
Paediatr Child Health Vol 16 No 9 November 2011
 Antidepressant use in children and adolescents

TAble 1
Factors to consider when initiating selective serotonin reuptake inhibitor (SSRI) use in children and youth
1. Evaluate for depression in
children and youth who present
with mood disturbances,
emotional problems
2. Confirm diagnosis and severity
of the condition
3. Assessment of parental/family
mental health
4. Suicidal risk at baseline?
5. Open discussion
6. Where to start therapy
7. When to start an SSRI?
8. Where to get started with an
SSRI: Do no harm
9. Acknowledge risks for
antidepressant
10. Review what other drugs are
currently being used and the risk for side effects or therapeutic failure). History of previous adverse reactions to psychotropic drugs, and concurrent use of
for adverse drug effects
11. Starting an antidepressant
12. Start low/go slow
13. Tracking goals and outcomes
14. Monitor for emergence of
adverse events/follow-up/
ongoing management
15. When to refer?
16. Taking advantage of the placebo Take advantage of the placebo response (found to be high in most adolescent depression trials). That is, invoke a similar
effect
17. Pharmacotherapeutic failure
18. Avoid therapeutic failure:
Develop collaborative care
network
Adapted from references 3, 5, 27 and 30
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
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)
Who else is depressed at home or is there a family history? History of suicide?
While measuring symptoms of depression at the initial assessment, special attention to suicidality needs to be documented
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.
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
Medications should be reserved for the treatment of moderate to severe conditions
Do a proper risk-benefit relationship analysis of the situation. Complete history/family history and assessment of risk
factors. Fully discuss the risks and benefits of medication with your patient/family
Check for signs and symptoms that may imply an increased risk of adverse effects (ie, risk for switch to mania). For
example, anxiety symptoms (especially panic), impulsivity/restlessness, agitation and history of mania/hypomania
Drug-drug interactions? Potential for therapeutic failure or toxicity? (Consider role of hepatic cytochrome 450 factors in risks
psychotropic medications that might increase risk for drug-drug interactions
Provide the patient and family with a detailed account of the possible adverse effects (both behavioural and somatic), and
the expected timelines to improvement. Document your discussion
Consider a low-test dose and ask for contact from the youth or caregiver if there is a problem in the first few days. 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
Goals should include improved functional status (school, home and peers) and lessening of depressive symptoms. Use the
World Health Organization’s International Classification of Functioning, Disability and Health framework to guide treatment
outcomes (ie, symptoms and function)
Observe closely for clinical worsening, suicidality and changes in behaviour during the initial few months of treatment or at
times when dose changes. 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
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 conditions), consultation with a psychiatrist is needed
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
Consider what else is going on: Consider drug-drug interactions, pharmacogenetic or dietary influences (ie, grapefruit)
What to do when you get ‘stuck’ with therapeutic failure? 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

illness, family dysfunction and academic failure. 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 estab-
lishing 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. The 2001 World Health Organization’s
International Classification of Functioning, Disability and Health
presents a useful model to help ensure comprehensiveness in
depression assessment and management. It reminds clinicians that it
is the combined effect of a health condition (such as MDD), along
with personal factors (the individual patient’s unique attributes and
resources) and environmental factors (family, friends and school),
that result in the impact on relevant health outcomes such as
psychological functioning, performing daily tasks and participating
in social activities (33). For paediatricians, flexibility in office/time
organization, staff training and links with community professions
can contribute to effective management of children and youth at
risk in an office setting.
Where symptoms are mild or the diagnosis is unclear, an initial
period of careful observation and active supportive therapy is war-
ranted. This should include a focus on management of comorbid
anxiety, functional needs, availability of self-help material and

Paediatr Child Health Vol 16 No 9 November 2011 551

Oberlander and Miller
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 (26,28,34). 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 (2,3,5,27,30)
suggests the deployment of combined treatment with both medica-
tion 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 continu-
ing 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 worsen-
ing of suicidality (11). As covered above, the best evidence sup-
ports the use of fluoxetine for depression (18,36), although this
drug has not been approved for use in Canada in children younger
than 18 years of age (5,27).
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 prop-
erly 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 mem-
brane (ie, serotonin transporter polymorphisms that regulate the
levels of the transporter protein), and the presence of concurrent
psychotropic 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 resolu-
tion 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,
552
psychiatrists, and associated health and education professionals.
The need for collaborative health care has been recently high-
lighted by a study of paediatricians in British Columbia who over-
whelmingly reported that children with mental health problems
need comprehensive team approaches with timely access to com-
munity resources (38). As we continue to face a paucity of child
psychiatrists, especially in communities outside of tertiary care
centres, developing models such as ‘shared care’ or collaborative
mental health networks are necessary (39,40). Such models can
offer coordination of complex care, interprofessional communica-
tion and facilitation of case-by-case support, which may avoid
‘therapeutic failure’. Emerging evidence suggests that shared care
models may be beneficial for the management of depression in
children (30). Such community-based teams can promote profes-
sional education, strengthening mental health services for the
child, family and professionals.
COnCLuSIOnS
Phenotypic variations and frequent comorbidities often lead to
diagnostic uncertainty, making the management of depression in
children and adolescents challenging. 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 manag-
ing childhood depression, paediatricians can play a critical role.
ACKnOWLEDgEMEnTS: The authors thank Ursula Brain for her
thoughtful editorial influence and skill in preparation of the manu-
script and Jane Garland for her insightful comments. They also thank
the Paediatrics and Child Health reviewers whose comments also
strengthen this paper. Dr Oberlander is supported by a Human Early
Learning Partnership (HELP) Senior Career Award and holds the
R Howard Webster Professorship in Child Development (University
of British Columbia, College of Interdisciplinary Studies). Dr Miller is
supported by the Sunny Hill Foundation for Children.
COnFLICTS OF InTEREST: The authors have no conflicts of
interest to declare.
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