Maintenance study for adolescent depression.
ABSTRACT Although recent studies and meta-analyses confirm the efficacy of antidepressants in the acute phase of treatment for adolescent depression, there are few data available to allow assessment of the value of continued use of antidepressants in depressed adolescents after acute response. This study examines the benefit of maintenance treatment with sertraline in adolescents aged 13-19 years with major depression using a multi-site randomized placebo controlled discontinuation design.
Subjects with a diagnosis of depression who responded to open-label treatment with sertraline in a 12-week acute phase and did not relapse with open-label continuation treatment for 24 weeks were randomized to placebo or continued treatment with sertraline for 52 weeks.
Twenty-two subjects were randomized to maintenance treatment with sertraline (n = 13) versus placebo (n = 9). A higher proportion of subjects treated with sertraline (38%) remained well as compared to those on placebo (0%). Survival analyses found no significant differences between the groups (p = 0.17).
This is the first study to examine the outcome to maintenance treatment for adolescents with major depression. Although the sample size was small, the findings suggest a possible benefit of maintenance treatment with sertraline over placebo. A larger clinical trial with adequate power is required to confirm or disconfirm these findings.
- Psychiatric Annals 04/2010; 40(4):192-202. · 0.71 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Desafortunadamente la prevalência de los trastornos depresivos en la adolescencia se ha visto incrementada en los últimos años. Un mayor diagnóstico no conlleva necesariamente a un tratamiento exitoso, debido, entre otros factores, a la pobre adherencia al tratamiento con medicamentos en la adolescencia. De hecho, los estudios en salud mental demuestran que un importante número de pacientes no adhieren a los tratamientos farmacológicos. Sin embargo, estos estudios se centran principalmente en pacientes adultos y pocos en la población infanto juvenil. Nuestro artículo tiene por objetivo conocer de un modo general los factores que están en juego en la adherencia a tratamiento medicamentosos antidepresivo en adolescentes con trastorno del ánimo, y describir un modelo que pueda ayudar a intervenir clínicamente en favor de una mayor adherencia terapéutica.Revista chilena de neuro-psiquiatría. 03/2011; 49(1):69-78.
- [Show abstract] [Hide abstract]
ABSTRACT: Direct-bandgap semiconductor with high quantum radiative efficiency can operate as a scintillator despite being “opaque” to its own luminescence. An interband absorption does not finish off the luminescence but merely creates a new minority carrier, which in turn recombines in a predominately radiative fashion. To take full advantage of this “photon recycling” effect, optically-tight integration of photoreceivers on both sides of the semiconductor scintillator wafer is desirable.Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment 10/2011; 652(1):292-294. · 1.32 Impact Factor
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
Volume 18, Number 4, 2008
© Mary Ann Liebert, Inc.
Maintenance Study for Adolescent Depression
Amy Cheung, M.D., Vivek Kusumakar, M.D., Stan Kutcher, M.D., Elyse Dubo, M.D., Jane Garland, M.D.,
Margaret Weiss, M.D., Alex Kiss, Ph.D., and Anthony Levitt, M.D.
Objective: Although recent studies and meta-analyses confirm the efficacy of antidepressants in the acute phase
of treatment for adolescent depression, there are few data available to allow assessment of the value of con-
tinued use of antidepressants in depressed adolescents after acute response. This study examines the benefit
of maintenance treatment with sertraline in adolescents aged 13–19 years with major depression using a multi-
site randomized placebo controlled discontinuation design.
Methods: Subjects with a diagnosis of depression who responded to open-label treatment with sertraline in a
12-week acute phase and did not relapse with open-label continuation treatment for 24 weeks were random-
ized to placebo or continued treatment with sertraline for 52 weeks.
Results:Twenty-two subjects were randomized to maintenance treatment with sertraline (n ? 13) versus placebo
(n ? 9). A higher proportion of subjects treated with sertraline (38%) remained well as compared to those on
placebo (0%). Survival analyses found no significant differences between the groups (p ? 0.17).
Conclusions: This is the first study to examine the outcome to maintenance treatment for adolescents with ma-
jor depression. Although the sample size was small, the findings suggest a possible benefit of maintenance
treatment with sertraline over placebo. A larger clinical trial with adequate power is required to confirm or dis-
confirm these findings.
that treatment of depressed adolescents with antidepres-
sants may be an effective means of providing relief from
acute symptomatology (Bridge et al. 2005). Although virtu-
ally all guidelines for the treatment of adolescent depres-
sion recommend that treatment continue beyond the acute
phase, the efficacy of maintenance antidepressant therapy
for depression in adolescents is unknown (AACAP 1998).
Evidence from the adult literature suggests that a signifi-
cant proportion of depressed patients not maintained on
treatment are at greater risk of recurrence of depressive
symptoms (Kocis et al. 2003). Treatment for depression is
often divided into three phases: the first 8–12 weeks is con-
sidered acute therapy, treatment from acute recovery up un-
til 6 months is considered continuation therapy, and treat-
ment beyond 6 months is considered maintenance therapy
ECENT META-ANALYSES EXAMINING THE EFFICACY of antide-
pressant treatment for adolescent depression suggest
(Frank et al. 1991). The “Practice Parameters” published by
the American Academy of Child and Adolescent Psychiatry
suggests “continuation therapy is necessary in all patients
after the acute phase” (AACAP 1998). However, despite the
growing literature on acute treatment of adolescent depres-
sion with antidepressants, there are little data from con-
trolled trials on long-term treatment with antidepressants.
In 2004, Emslie et al. reported the results of a continuation
study with fluoxetine in 40 depressed adolescents. Subjects
who responded after 22 weeks were randomized to placebo
or continued fluoxetine for 8 months. Subjects on placebo
were more likely to relapse compared to those who re-
mained on fluoxetine (Emslie et al. 2004). Emslie and col-
leagues recently replicated these findings (Emslie 2008). De-
spite this emerging evidence for continuation treatment,
there are no randomized controlled trials data regarding the
relative risks or benefits of longer term, or maintenance
treatment with antidepressants. Therefore, this study was
designed as a randomized controlled trial of maintenance
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Clinical Trials Registry: http:/ /www.clinicaltrials.gov; Registration number: NCT00508859
treatment of sertraline in adolescents aged 13–19 years with
Subjects aged 13–19 years were recruited, over 18 months
(1997–2000), at mood disorders clinics in three tertiary care
centers across Canada. Informed consent was obtained from
eligible and interested subjects and parents (if subject was
?16 years of age). Subjects were eligible for entry into the
study if they had a diagnosis of major depression, deter-
mined from both clinical interview and the Schedule for Af-
fective Disorders and Schizophrenia for Children (K-SAD-
PL) and scored ?16 on the first 17 items of the 29-item
Hamilton Rating Scale for Depression (HAM-D) (Kaufman
et al. 1997, Hamilton 1960). Subjects were excluded if they
had past or current hypomanic or manic episode, current
psychotic symptoms, substance dependence in the last 3
months, significant medical condition that would con-
traindicate the use of antidepressants or that if untreated
may require medical attention, current pregnancy, or past
treatment with sertraline for major depression.
Interventions and procedures
There were three phases to the study: a) a 12-week acute
phase, b) a 24-week continuation phase, and c) a 52-week
maintenance phase. Initial sertraline dose during the acute
phase was either 25 mg or 50 mg daily with increases of 25
to 50 mg every 2 weeks at the treating clinicians’ discretion,
up to a maximum of 200 mg daily. Subjects were assessed
every 2 weeks throughout this phase. Those who responded
to acute phase treatment, defined as two consecutive HAMD
?9 and greater than a 50% reduction in HAM-D score within
12 weeks, were offered entry into the continuation phase.
For responders who entered the continuation phase and
had some re-emergence of symptoms without relapse, dose
increases with sertraline were permitted every 2 weeks to a
maximum dose of 200 mg daily but only during the first 8
weeks of this phase. If a subject experienced side effects, one
dose decrease was permitted in the first 8 weeks of the con-
tinuation phase. Subjects in this phase were also assessed
every 2 weeks, and every second visit was conducted in per-
son while the other assessments could be conducted either
by telephone or in person. Relapse during the continuation
phase was determined according to the clinical judgment of
the treating physician or if an intervention beyond what was
permitted by the study protocol was required.
Subjects who maintained response during continuation
were randomized to continue sertraline or to take placebo.
Randomization was conducted by the study pharmacist us-
ing a computer-generated randomization schedule. Subjects,
clinicians, and research staff remained blinded to treatment
during the randomization phase. In the placebo group, ser-
traline was tapered by 25% of the initial dose every week for
CHEUNG ET AL.390
Figure 1: Patient Flow in Maintenance Phase
51 Eligible to enter continuation phase
93 Enrolled in acute phase
22 Randomized into maintenance phase
Continuation Phase Patient Disposition
9 relapsed, plus
8 lost to follow-up
2 non-compliant with medication
2 switched to mania/hypomania
5 withdrew consent
3 developed substance abuse
9 assigned Placebo
All received assigned treatment
13 assigned Sertraline
All received assigned treatment
1 lost to follow-up
1 withdrew consent
(All considered recurred in analyses)
5 recurrence free
1 lost to follow-up
(Considered as recurred in analyses)
13 included in analyses
9 included in analyses
Acute Phase Patient Disposition
17 non-responders, plus
1 developed psychosis
1 switched to mania/hypomania
13 lost to follow-up
6 non-compliant with medication
1 switched to unprescribed
1 withdrew consent
2 had side effects
Subject flow and disposition.
the first 4 weeks of the maintenance phase. During the main-
tenance phase, no treatment changes were permitted. Sub-
jects were assessed every 2 weeks except during the first 4
weeks when they were seen or contacted weekly. In this fi-
nal phase, every second visit was also conducted in person
while the other assessments could be conducted either by
telephone or in person. Recurrence during maintenance
phases was determined according to the clinical judgment
of the treating physician that the major depression had re-
curred or if an intervention beyond what was permitted by
the study protocol was required.
Inter-rater reliability for the HAM-D was tested annually
with site project coordinators and research assistants. Fur-
ther training and evaluation were implemented until the in-
ter-rater reliability was 0.8 or greater. As described above,
relapse during the continuation and recurrence during main-
tenance phases were determined according to the clinical
judgment of the treating physician or an intervention beyond
what was permitted by the study protocol was required. The
HAM-D score was not used to determine relapse or recur-
rence but the results of the HAM-Ds were available to the
treating physician when determining clinical status. This
clinical judgment was based on the presence of depressive
symptoms and level of impairment. Unfortunately, it is vir-
tually impossible to standardize the concept of clinical judg-
ment. We chose it as a pragmatic outcome that reflects what
occurs in everyday clinical practice, and to ensure that clin-
icians felt free to make alterations in treatment in this sus-
Adverse events were collected using the Common Ad-
verse and Side Effects Scale (CASES). The scale was admin-
istered every 2 weeks during the acute phase and every 4
weeks during the continuation and maintenance phase. The
CASES did not include any suicide items and no suicide in-
struments were included in the study. Therefore, worsening
or new onset suicidality was captured only by spontaneous
reporting by subjects.
Survival analyses were conducted based on the primary
outcome (time to clinical recurrence) in the maintenance
phase. Subjects who were randomized and who received at
least one dose of treatment/placebo were included in the
analyses. A log rank test was run assessing for the effects of
treatment assignment. A secondary survival analysis was
run controlling for the possible influence of gender and base-
line HAM-D scores (at entry to the acute phase) on the like-
lihood of recurrence during the maintenance phase. All
analyses were run using SAS version 9.1(SAS Institute, Cary,
NC). All statistical analyses were conducted by an indepen-
dent statistician blinded to patient allocation.
Ninety-three subjects were eligible and consented to par-
ticipate. Average age of subjects at enrolment was 15.9 years,
with 73% female. A detailed description of subject flow and
disposition is shown in Figure 1 (CONSORT Flow Diagram).
At the end of the continuation phase, 22 subjects were eligi-
ble to enter the maintenance phase and were randomized.
None of the 9 subjects in the placebo group maintained re-
sponse (no recurrence) during the 52-week randomization
phase. In contrast, 5 of 13 subjects (38%) in the sertraline
group remained well.
Table 1 shows some of the characteristics and treatment
course of the subjects who entered the randomization phase.
There were no significant differences found between the ser-
traline and placebo groups in terms of percentage female
ADOLESCENT DEPRESSION 391
TABLE 1.SUBJECT CHARACTERISTICS IN MAINTENANCE PHASE
(n ? 22)
(n ? 13)
(n ? 9)
Mean age (range)a
19.9 (3.8)Mean baseline
HAM-D at acute entry (SD)a
Comorbid anxiety disorder (%)a
Previous depressive episodes (%)a
Recurrence free (%)b
Mean time to recurrence
Mean change in HAM-D
Mean HAM-D score at exit
—7.3 (8.6)9.4 (7.3)
— 11.3 (9.2) 12.4 (8.3)
aNo statistically significant differences between the placebo and sertraline groups.
bFisher’s exact test (p ? 0.054).
cMean change as measured from entry to exit during the maintenance phase.
HAM-D,Hamilton Rating Scale for Depression; SD, standard deviation.
(Fisher’s Exact, p ? 0.99), comorbid anxiety (Fisher’s Exact,
p ? 0.99), number of previous episodes of depression
(Fisher’s Exact, p ? 0.24), mean age (t ? ?1.68, p ? 0.11) or
mean baseline HAM-D scores at entry to the acute phase (t ?
?0.82, p ? 0.42). There were also no significant differences
between the two groups based on exit HAM-D scores.
The survival curve for the two treatment arms is presented
in Figure 2. The log rank test did not find drug assignment
to be significant (?2(1) ? 1.92, p ? 0.17). In the secondary
analyses, none of the variables, drug assignment (?2(1) ?
0.34, p ? 0.56), gender (?2(1) ? 1.21, p ? 0.27), or HAM-score
at entry to acute phase (?2(1) ? 0.09, p ? 0.77) had a signifi-
cant independent impact on the outcome. The median time
to exit in the sertraline group was 12.5 weeks and in the
placebo group was 10 weeks. Because of the small sample
size, we also calculated the mean number of weeks
(placebo ? 16.4 weeks, sertraline ? 29.3 weeks). No differ-
ences were found in the attrition rate when compared be-
tween the placebo or sertraline groups (Fisher’s Exact, p ?
Six subjects (6%) discontinued the study due to adverse
effects: a) agitation and hostility (n ? 2), b) psychosis (n ?
1), and c) mania (n ? 3). There were no spontaneous reports
of new onset or worsening suicidality in any subjects dur-
ing the study. There were no serious adverse events reported
during the course of the study. Table 2 shows the general
rates of adverse effects at each phase of the study: acute, con-
tinuation, and maintenance. The most common adverse ef-
fects during the 12-week acute phase and 24-week continu-
ation phase which affected more than half of the study
subjects were fatigue, drowsiness, irritability, agitation, anx-
iety, and inner tension. During the maintenance phase, sev-
eral adverse effects were numerically more likely to affect
subjects on sertraline compared to those on placebo (?5%
difference) including fatigue, drowsiness, dizziness, tremor,
weight gain, headache, lightheadedness, irritability, sweat-
ing, and sexual dysfunction. Similarly, there were several ad-
verse effects that were numerically more likely to affect sub-
jects on placebo compared to those on sertraline (?5% dif-
ference) including rash, hypersomnia, anxiety, inner tension,
dry mouth, nausea/vomiting, diarrhea, runny nose, weight
loss, decreased/increased appetite, abnormal movements,
and cough. The two groups (drug and placebo) were com-
pared for differences in the number of patients experiencing
these side effects using chi-square tests or Fisher’s exact tests
in the case of small cell sizes. No significant differences were
This is the first study to examine the benefit of mainte-
nance treatment with antidepressants in adolescents with de-
pression after response to acute and continuation treatment.
Despite the problems with retention, there were important
findings. First, the results suggest that maintenance treat-
ment may be beneficial to youth with major depressive dis-
order. Evidence from the adult literature consistently dem-
onstrates that continued treatment with antidepressants after
acute response is critical in preventing recurrence in patients
with major depression (Franchini et al. 1999, Perahia et al.
2006, Reynolds et al. 2006) and there is emerging evidence
that the same is true for the adolescent population (Emslie
et al. 2004). Although the sample size of this study was small,
the findings confirm this emerging trend. In light of these
findings, clinicians managing adolescents with depression
may wish to consider longer term treatment with antide-
pressants in order to prevent recurrence. However, several
issues still need to be clarified regarding treatment after
acute response to antidepressant treatment. First, informa-
tion regarding the benefit of treatment during the continua-
tion phase is limited and no published study has directly as-
sessed the benefit of maintenance treatment. We found that
38% of subjects remained well in the maintenance phase. Sec-
ond, this study examined the benefit of one of the medica-
tions in the SSRI class, sertraline. It is unclear whether these
results can be extrapolated to other drugs in the same class.
As reported in the recent re-analyses of safety data on SSRIs
by the Food and Drug Administration, there appears to be
possible differences in both efficacy and safety among the
different SSRIs in youth with depressive disorders. In addi-
tion, emerging data from the adult literature also indicate
there may be within class differences in adverse effects. Un-
til there are further data from other maintenance studies with
different SSRIs, it is premature to suggest that there is or is
not a class effect.
The long-term data from this study also shed light on sev-
eral important issues regarding adverse effects. First, the re-
sults confirm that adverse effects are common in youth treated
with antidepressants. The most common adverse effects, af-
fecting more than 60% of the subjects on open-label treatment,
were fatigue, anxiety, and irritability. Second, very few sub-
jects withdrew from the study due to adverse effects. In fact,
the long held clinical belief regarding the high likelihood of
switching to mania in youth treated with antidepressants was
not confirmed by our results. The over-all rate of mania in our
sample was only 3% (n ? 3). Finally, no subjects withdrew
from the study due to worsening or new onset suicidality. Un-
fortunately, the findings on suicidality in this study are lim-
ited due to the lack of the inclusion of a specific suicide in-
CHEUNG ET AL. 392
?2(1) ? 1.92, p ? 0.17
Relapse-free probabilities between sertraline and
strument. This is consistent with other earlier studies con-
ducted with antidepressants in adolescents and children where
suicidality was not considered an adverse event but rather, an
outcome from the illness itself. With the recent controversy
around the safety of antidepressants and the Food and Drug
Administration’s black-box warning, if this study was being
conducted today, there would be a much greater emphasis on
the evaluation of suicidality.
Several issues limit our ability to generalize the results of
this study to the larger population of adolescents with de-
ADOLESCENT DEPRESSION 393
TABLE 2.PERCENTAGE OF ADVERSE EFFECTS DURING PHASES OF THE STUDY
(n ? 93)
(n ? 51)
(n ? 9)
(n ? 13) Adverse effects
*Denotes ?5% difference between placebo and sertraline groups. No significant differ-
ences found between the two groups on each of these adverse effects.
pressive disorders. First, the sample size of this study was
small. The low retention rate in the open-label phase im-
pacted on the number of subjects randomized. Second, ado-
lescents may present with any one of several depressive dis-
orders (i.e., dysthymia), each of which is commonly treated
with antidepressants. This study only included subjects with
major depressive disorder and we did not capture the full
spectrum of depressive disorders that present in adoles-
cence. However, even with the small sample size and the
limited focus on a specific clinical population, this is the first
study to examine maintenance treatment with an SSRI in
youth with depression. Findings from this study may be
used to guide future research examining the efficacy of an-
tidepressants in preventing recurrence after acute treatment.
This study was funded by the Canadian Institutes of
Health Research (CIHR). Dr. Cheung would like to ac-
knowledge the support of the RCT Mentoring Program,
Dr. Alex Kiss was the statistical expert.
Dr. Kusumakar is currently an employee of Johnson and
Johnson Pharmaceutical R &D. At the time of the study, Dr.
Kusumakar was a professor at Dalhousie University, Hali-
fax, Nova Scotia, Canada. Dr. Cheung was on the speaker’s
bureau of Eli Lilly (2004–2005). Dr. Levitt has been reim-
bursed by Eli Lilly for attending a symposium and for speak-
ing. He has also received fees from Wyeth Pharmaceuticals
for organizing an educational event and received funds for
research from Lundbeck, Wyeth, GlaxoSmithKlein, Roche,
and Servier. Dr. Levitt has also received fees for consulting
for Janssen, Eli Lilly, Wyeth, Organon, Pfizer, Glaxo-
SmithKlein, and Lundbeck. Drs. Kutcher, Dubo, Garland,
Weiss, and Kiss have no conflicts of interest or financial ties
Bridge JA, Salary CB, Birmaher B, Asare AG, Brent DA: The risks
and benefits of antidepressant treatment for youth depression.
Ann Med 37:404–412, 2005.
Emslie GJ, Heiligenstein JH, Hoog SL, Wagner KD, Findling RL,
McCracken JT, Nilsson ME, Jacobsen JG: Fluoxetine treatment
for prevention of relapse of depression in children and ado-
lescents: A double-blind, placebo-controlled study. J Am Acad
Child Adolesc Psychiatry 43:1397–1405, 2004.
Emslie GJ, Kennard BD, Mayes TL, Nightingale-Teresi J, Carm-
mody T, Hughes CW, Rush AJ, Tao R, Rintelmann JW: Flu-
oxetine versus placebo in preventing relapse of major de-
pression in children and adolescents. Am J Psychiatry. 2008
Franchini L, Zanardi R, Gasperini M, Smeraldi E: Two-year
maintenance treatment with citalopram, 20 mg, in unipolar
subjects with high recurrence rate. J Clin Psychiatry
Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW,
Rush AJ, Weissman MM: Conceptualization and rationale for
consensus definitions of terms in major depressive disorder.
Remission, recovery, relapse, and recurrence. Arch Gen Psy-
chiatry 48:851–855, 1991.
Hamilton M: A rating scale for depression. J Neurol Neurosurg
Psychiatry 23:56–62, 1960.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P,
Williamson D, Ryan N: Schedule for Affective Disorders and
Schizophrenia for School-Age Children-Present and Lifetime
Version (K-SADS-PL): Initial reliability and validity data. J
Am Acad Child Adolesc Psychiatry 36:980–988, 1997.
Kocsis JH, Rush AJ, Markowitz JC, Borian FE, Dunner DL, Ko-
ran LM, Klein DN, Trivedi MH, Arnow B, Keltner G, Korn-
stein SG, Keller MB: Continuation treatment of chronic de-
pression: A comparison of nefazodone, cognitive behavioral
analysis system of psychotherapy, and their combination. Psy-
chopharmacol Bull 37:73–87, 2003.
Perahia DG, Gilaberte I, Wang F, Wiltse CG, Huckins SA,
Clemens JW, Montgomery SA, Montejo AI, Detke MJ: Dulox-
etine in the prevention of relapse of major depressive disor-
der: Double-blind placebo-controlled study. Br J Psychiatry
Practice parameters for the assessment and treatment of chil-
dren and adolescents with depressive disorders. AACAP. J
Am Acad Child Adolesc Psychiatry 1998;37:63S–83S, 1998.
Reynolds CF, III, Dew MA, Pollock BG, Mulsant BH, Frank E,
Miller MD, Houck PR, Mazumdar S, Betters MA, Stack JA,
Schlernitzauer MA, Whyte EM, Gildengers A, Karp J, Lenze
E, Szanto K, Bensasi S, Kupfer DJ: Maintenance treatment of
major depression in old age. N Engl J Med 354:1130–1138,
Address reprint requests to:
Amy Cheung, M.D.
Sunnybrook Health Sciences Centre
2075 Bayview Avenue
CHEUNG ET AL. 394
This article has been cited by:
1.Cesar Soutullo, Ana Figueroa-Quintana. 2013. When do you Prescribe Antidepressants to Depressed Children?. Current Psychiatry
Reports 15:7. . [CrossRef]
2.Georgina R Cox, Patch Callahan, Rachel Churchill, Vivien Hunot, Sally N Merry, Alexandra G Parker, Sarah E Hetrick,
Georgina R CoxPsychological therapies versus antidepressant medication, alone and in combination for depression in children
and adolescents . [CrossRef]
3.Georgina R Cox, Caroline A Fisher, Stefanie De Silva, Mark Phelan, Olaoluwa P Akinwale, Magenta B Simmons, Sarah E Hetrick,
Georgina R CoxInterventions for preventing relapse and recurrence of a depressive disorder in children and adolescents . [CrossRef]
4.Christine J. Choe, Graham J. Emslie, Taryn L. Mayes. 2012. Depression. Child and Adolescent Psychiatric Clinics of North America
21:4, 807-829. [CrossRef]
5.Rongrong Tao, Graham Emslie, Taryn Mayes. 2010. Pharmacotherapy for Pediatric Major Depression. Psychiatric Annals 40:4,
6.Depression and anxiety 155-250. [CrossRef]