Boafo et al.

Child Adolesc Psychiatry Ment Health (2020) 14:10 Child and Adolescent Psychiatry
https://doi.org/10.1186/s13034-020-00316-8
and Mental Health

RESEARCH ARTICLE Open Access

Medications for sleep disturbance in children

and adolescents with depression: a survey
of Canadian child and adolescent psychiatrists
Addo Boafo1,2,3*  , Stephanie Greenham1,4, Marla Sullivan1, Khalid Bazaid1,2, Sinthuja Suntharalingam1,2,
Lana Silbernagel2, Katherine Magner1 and Rébecca Robillard3,4

Abstract 
Background:  Primary care physicians and child and adolescent psychiatrists often treat sleep disturbances in chil-
dren and adolescents with mood disorders using medications off-label, in the absence of clear evidence for efficacy,
tolerability and short or long-term safety. This study is the first to report Canadian data about prescribing preferences
and perceived effectiveness reported by child and adolescent psychiatrists regarding medications used to manage
sleep disturbances in children and adolescents with depression.
Methods:  Canadian child and adolescent psychiatrists were surveyed on their perception of effectiveness of a range
of medications commonly prescribed for sleep disturbances, their ranked preferences for these medications, reasons
for avoiding certain medications, and perceived side effects.
Results:  Sixty-seven active child and adolescent psychiatrists completed the survey. Respondents reported noting
significant sleep issues in 40% of all their patients. Melatonin and trazodone were identified as the first treatment of
choice by 83% and 10% of respondents respectively, and trazodone was identified as the second treatment of choice
by 56% of respondents for treating sleep disturbances in children and adolescents with depression. Melatonin (97%),
trazodone (81%), and quetiapine (73%) were rated by a majority of respondents as effective. Doxepin, zaleplon, tricy-
clic antidepressants, zolpidem, or lorazepam were rarely prescribed due to lack of evidence and/or concerns about
adverse effects, long-term safety, suitability for youth, suicidality, and dependence/tolerance.
Conclusions:  Melatonin and certain off-label psychotropic drugs are perceived as being more effective and appro-
priate to address sleep disturbances in children and adolescents with depression. More empirical evidence on the effi-
cacy, tolerability and indications for using these medications and newer group of sleep medications in this population
is needed.
Keywords:  Sleep medications, Depression, Children, Adolescents

Background many individuals. Pediatric depression is character-

Changes in sleep and biological rhythms emerge dur- ized by prolonged or recurrent sadness or irritability,
ing childhood and adolescence [1, 2]. This developmen- markedly diminished interest or pleasure in activities,
tal period also marks the onset of mood disorders for decrease or increase in appetite, feelings of restlessness
or being slowed down, poor memory and concentration,
feelings of worthlessness and guilt, recurrent thoughts
*Correspondence: [email protected]
1
of death, as well as sleep disturbances [3]. Its prevalence
Mental Health Program, Children’s Hospital of Eastern Ontario, 401
Smyth Road, Ottawa, ON KH 8L1, Canada
increases in the early teens, more so in girls than boys
Full list of author information is available at the end of the article [4]. A survey of Canadians aged 15 to 24 years indicated

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Boafo et al. Child Adolesc Psychiatry Ment Health (2020) 14:10 Page 2 of 8

that about 11% have experienced depression in their life- a sleep medication than those seeing a general/family
time, and 7% reported depression in the previous year practice physician [25]. A national survey in the United
[5]. In childhood and adolescence-onset depression, the States reported that trazodone was the most commonly
risk of recurrence is high, about 50 to 70% within 5 years, prescribed sleep medication by psychiatrists for children
and persisting depression is associated with worse sui- with mood or anxiety disorders [23]. However, this study
cidality [6]. Suicide is one of the leading cause of death is now over a decade old and an update on current clini-
among Canadian adolescents [7], and rates of suicide cal knowledge and experience is warranted.
are increasing in this age group [8]. Poor sleep has been The current study aims to make use of clinical expe-
linked to worse and more recurrent depression, as well rience to generate more information about pharma-
as increased suicidal ideation in adolescents [9]. Yet, lit- cological sleep treatments in the context of pediatric
tle is known about how sleep disturbances co-occurring depression. It reports on prescribing preferences and
with depression are addressed in current pedopsychiatric perceived effectiveness reported by Canadian child and
practice. adolescent psychiatrists regarding their use of medica-
Sleep disturbances are estimated to affect 66% to 72% tions for managing sleep disturbances in children and
of children and adolescents with depression [10, 11], and adolescents with depression.
sleep loss was found to predict higher risks of depression
in young Canadians [12]. These sleep problems can inter- Methods
fere with antidepressant response to standard treatments Design and study population
[13]. For instance, it is suspected that medications pre- A 16-item survey was sent to 433 members of the
scribed for depression may not be better than placebo in Canadian Academy of Child and Adolescent Psychiatry
patients who also have sleep disturbances [14]. Further- (CACAP) between October and December 2016. A fol-
more, residual sleep problems after depression remission low-up letter urging participation was sent 4 weeks after
increase the risk of relapse [15, 16], and treating sleep the initial mail-out. The opportunity to enter a draw for a
disturbances in youths can improve depression [17, 18]. 1-year CACAP membership (valued at $325) or the reg-
The use of medications prescribed for adult depression istration fee to the annual CACAP conference (valued at
in youth is controversial; with concerns of modest thera- $450) were offered as incentives. The Children’s Hospital
peutic effects and higher risks for side effects, leading to of Eastern Ontario Research Ethics Board approved the
questionable overall benefits-to-risk ratios [19, 20]. There study.
is even less clarity for medications targeting sleep and
circadian rhythms. Although there is no official approval, Survey instrument
indication, or dosing guidelines for their use in children The survey designed by the research team was available
and adolescents, off-label treatment of sleep disturbances in English and French, and could be filled either on paper
with over-the-counter and prescription medications are or on REDCap [26]. Prior to distribution, it was piloted
common [21]. There is inadequate information about the with a small number of child psychiatrists for clarity of
short-term and long-term tolerability, safety, and efficacy content and readability. A copy of the final survey items
of sleep promoting medications and products in youth is provided in Additional file 1.
[22, 23]. As such, the Federal Drug Agency in the United Demographic questions (gender, years of active clinical
States of America (FDA) does not approve the use of practice, location of services, characteristics of the work
sleep promoting medications and products under the age setting, faculty appointment, and frequency of sleep dis-
of 18 years, and Health Canada only approved the use of turbance in child and adolescent patients) were based on
diphenhydramine. previous surveys from the College of Family Physicians
Considering the paucity of empirical evidence in pedi- of Canada, the Canadian Medical Association, and the
atric populations, observational data of current practice Royal College of Physicians and Surgeons of Canada. The
and clinical impressions represent an important source of remaining questions were specifically designed to inves-
information. A study investigating prescription habits of tigate prescribing preference and perceived effectiveness
Canadian general practitioners and pediatricians for chil- to treat sleep disturbances in children and adolescent
dren and adolescents with sleep problems reported that patients with depression with the following sleep pro-
melatonin, antihistamines, antidepressants and even ben- moting medications: antihistamines, doxepin, lorazepam,
zodiazepines were the most commonly used [24]. How- other benzodiazepines, melatonin, mirtazapine, quetia-
ever, prescription habits to address sleep difficulties may pine, trazodone, tricyclic antidepressants, tryptophan,
differ in the context of pediatric mood disorders. This is zaleplon, zolpidem, zopiclone, and herbals (e.g., valerian,
especially relevant since children and adolescents seeing lavender). Specifically, these questions asked about: (a)
a psychiatrist are 3.6 times more likely to be prescribed perceptions of effectiveness for each medication; (b) first
 Boafo et al. Child Adolesc Psychiatry Ment Health (2020) 14:10 Page 3 of 8

and second prescription choices; (c) medication(s) never Table 1  Sample characteristics
prescribed (indicating the reason by selecting one of the
Gender (% female) 53.7
following options: lack of effect, concerns in youth, off
Years of active clinical practice (%)
label status, adverse effects, agitation, suicidality, long
 Less than 2 years 4.5
term safety, dependence or tolerance, lack of evidence);
 2 to 5 years 9.0
and (d) most common side effect observed (excessive
 6 to 10 years 14.9
sedation, daytime fatigue, nightmares or dreaming, agita-
 11 to 20 years 32.8
tion, dizziness, headache, memory impairment, postural
 More than 20 years 38.8
orthostatic or tachycardia effects, or not applicable/do
New patients per week (Mdn) 4 (IQR 2–8)
not use).
Patients with significant sleep difficulties (Mdn %) 40.0 (IQR 23.8–52.5)
Province/territory (%)
Exclusion criteria
 Nova Scotia 6.0
Surveys were systematically excluded for respondents
 New Brunswick 1.5
who: were not child or adolescent psychiatrists, had not
 Quebec 10.4
seen a child or adolescent patient within the previous
 Ontario 49.3
12 months, or filled out less than 60% of the items.
 Manitoba 4.5
 Saskatchewan 3.0
Statistical analyses
 Alberta 7.5
For descriptive purposes, medians and standard devia-
 British Columbia 17.9
tions (or interquartile range (IQR) for skewed values)
 Others 0
were calculated for continuous variables, and categorical
Primary work setting (%)
variables were summarized using percentages and fre-
 Academic/Tertiary Care Hospital 46.3
quencies. Chi-square analyses were conducted to com-
 Community Hospital 13.4
pare differences in the proportions of psychiatrists rating
 Community Health Centre 11.9
the main types of medications as first and second choices
 Private practice 16.4
stratified by years of practice and practice settings. Data
 Other/multiple settings 10.4
was analyzed using IBM SPSS Statistics for Windows
Primary service type (%)
[27].
 Inpatient services 10.4
 Outpatient services 61.2
Results
 Mix of both inpatient and outpatient 26.9
Sample characteristics
Type of community (%)
Of the 433 surveys mailed, 74 were returned (17.1%
 Urban/suburban 88.1
response rate). Of this sample, 67 (15.5%) surveys were
 Rural/small town 10.4
cleared from the exclusion criteria. The majority of sur-
 Remote 0
veys were completed in English (94.0%). Sample charac-
Faculty appointment (% yes) 77.6
teristics are presented in Table 1.
Mdn median, province/territories—others Northwest Territories, Newfoundland/
Labrador, Prince Edward Island, Nunavut, Yukon
Perceived effectiveness and ranked preferences to treat
sleep disturbances
Melatonin was perceived by 97.0% of respondents as for trazodone (Fig.  1a). There was no significant differ-
effective, followed closely by trazodone (81.5%) and ence in the proportion of respondents identifying mela-
quetiapine (73.8%) (Table  2). Mirtazapine (55.4%) and tonin as second choice or trazodone as a first or second
zopiclone (52.3%) were also perceived to be effective choice across subgroups based on years of experience
by about half of respondents. Respondents most fre- (Fig. 2a, all p > 0.050).
quently reported melatonin and trazodone as their first There was no significant difference in rates of first
and second choices respectively. Most respondents indi- choice medications between respondents from academic/
cated that they never prescribe doxepin (87.9%), zale- tertiary settings compared to those from community
plon (86.6%), tricyclic antidepressants (83.3%), zolpidem settings (all p > 0.050, Fig.  1b). There was a significantly
(77.6%), or lorazepam (68.2%) to treat sleep disturbances higher proportion of respondents who identified trazo-
in pediatric depression. done as their second choice in academic/tertiary settings
The proportion of respondents who identified mela- compared to community settings (χ2(1) = 5.4, p = 0.020;
tonin as their first choice decreased with the number of Fig.  2b). No other difference in rates of second choice
years of experience, and the opposite pattern was found
Boafo et al. Child Adolesc Psychiatry Ment Health (2020) 14:10 Page 4 of 8

Table 2  Perceived effectiveness and prescribing preferences

Medication Find it effective (%) First choice for treatment (%) Second choice for treatment Never
(%) prescribe
(%)

Melatonin 97.0 83.3 3.1 3.0

Trazodone 81.5 10.6 56.9 12.1
Quetiapine 73.8 0.0 12.3 24.2
Mirtazapine 55.4 1.5 6.2 31.8
Zopiclone 52.3 1.5 4.6 52.3
Other benzodiazepines 25.4 0.0 1.5 54.5
Antihistamines 23.4 0.0 0.0 60.6
Lorazepam 19.4 0.0 1.5 68.2
Tricyclic antidepressants 16.9 0.0 0.0 83.3
Tryptophan 16.9 3.0 4.6 65.7
Doxepin 9.5 0.0 1.5 87.9
Zolpidem 7.8 0.0 1.5 77.6
Herbals 6.3 0.0 0.0 62.1
Zaleplon 1.6 0.0 0.0 52.3
%: Percentage of respondents endorsing each medication type as being effective, being their first or second choice of treatment, or as a drug that they never
prescribe for sleep difficulties in children and adolescents with depression

a b
100
100
Academic Setting
Less than 10 years 90
90 Community Setting
11 to 20 years
80
First Choice Prescription (%)

80
First Choice Prescription (%)

20+ years
70
70
60
60
50
50
40
40
30
30
20
20
10
10
0
0
Melatonin Trazodone Tryptophan
Melatonin Trazodone Tryptophan
Fig. 1  First choice prescriptions. Percentages of respondents who rated melatonin, trazodone and tryptophan as first choice for treatment of sleep
disturbance in children and adolescents with depression as a function of years of clinical experience and practice setting

medications based on respondents’ settings reached sta- These results were similar for quetiapine, with greater
tistical significance (all p > 0.050). perceived negative side effects of excessive sedation
(58.2%) and daytime fatigue (49.3%). Of note, 22.4% of
respondents reported having concerns regarding the
Perceived risks and side effects long-term safety of quetiapine.
Table 3 reports perceived side effects for the most fre- As for medications reported as the least frequently
quently preferred medications. For melatonin, the most prescribed (doxepin, zaleplon, tricyclic antidepressants,
commonly reported perceived side effects by respond- zolpidem, and lorazepam), most respondents reported
ents were: nightmares (16.4%), headache (9.0%), and they avoided them because of: dependence or toler-
fatigue (9.0%). Trazodone was frequently perceived to ance, concerns about their use in youth, adverse effects,
cause excessive sedation (37.3%) and fatigue (35.8%).
 Boafo et al. Child Adolesc Psychiatry Ment Health (2020) 14:10 Page 5 of 8

lack of evidence, and long-terms safety concerns (see disturbances in that population. Specifically, melatonin
Table 4). and trazodone were identified as the first treatment of
choice by 83% and 10% of respondents respectively,
Discussion and trazodone was identified as the second treatment
This is the first report about prescribing preferences of choice by 56% of respondents. Melatonin was also
and perceived effectiveness reported by Canadian child perceived as having the least side effects. While there
and adolescent psychiatrists regarding the use of sleep is a pressing need for empirical data on this topic, these
medications in children and adolescents with depres- findings derived from clinical experience increase the
sion. The results indicate that a majority of Canadian knowledge base on pharmacotherapies for the man-
child and adolescent psychiatrists perceive melatonin, agement of sleep problems in the context of pediatric
trazodone, and quetiapine as effective in treating sleep depression.

Fig. 2  Second choice prescriptions. Percentages of respondents who rated melatonin, trazodone and tryptophan as second choice for treatment
of sleep disturbance in children and adolescents with depression as a function of years of clinical experience and practice setting

Table 3  Perceptions about side effects

Nightmares (%) Daytime fatigue (%) Headache (%) Excessive sedation (%) Long-term
safety (%)

Melatonin 16.4 9.0 9.0 3.0 4.5

Trazodone 11.9 35.8 13.4 37.3 6.0
Quetiapine 4.5 49.3 3.0 58.2 22.4
%: Percentages of respondents who noticed various side effects when prescribing melatonin, trazodone and quetiapine (i.e. the three medications which were rated
by the most respondents as effective)

Table 4  Reported concerns

Long-term safety Adverse effects Lack of evidence Concerns in youth Dependence/ Suicidality (%)
(%) (%) (%) (%) tolerance (%)

Doxepin 22.4 31.3 22.4 17.9 3.0 3.0

Zaleplon 16.4 20.9 22.4 35.8 29.9 0.0
Tricyclics 22.4 59.7 22.4 37.3 1.5 20.9
Zolpidem 16.4 20.9 20.9 34.3 32.8 0.0
Lorazepam 29.9 31.3 10.4 38.8 76.1 6.0
%: Percentages of respondents who reported various concerns about the less commonly prescribed medications
Boafo et al. Child Adolesc Psychiatry Ment Health (2020) 14:10 Page 6 of 8

Over 10  years ago, a study on American psychiatrists Low doses of quetiapine are also commonly prescribed
reported that trazodone was the most commonly pre- for sleep disorders, although this indication has not
scribed sleep medication for children with mood and been officially approved and concerns were raised about
anxiety disorders, reaching a prescription rate of 78%, potential adverse effects (e.g. fatal hepatotoxicity, QT
while alpha-2 agonists were prescribed 40% of the time prolongation and akathisia). Nevertheless, the perceived
[23]. Conversely, melatonin was recommended by a efficacy of these two drugs based on clinical observations
third of respondents. A more recent report on Ontario reported in the current study suggest that they may be
pediatricians and family physicians noted that melatonin relevant medications to investigate further in children
(73%), over-the-counter antihistamines (41%), antide- and adolescents with depression and sleep complaints.
pressants (37%), and benzodiazepines (29%) were the In the current study, the majority of respondents
most commonly recommended medications [24]. Overall reported never prescribing antihistamines for insomnia
differences in prescription preferences between the cur- in depressed youth, but 22% did report finding it to be
rent findings and these past studies suggest that mela- effective. The latter conflicts with studies showing that
tonin is increasingly used to address sleep problems in H1 antihistamines are no more effective than placebo
youths with depression. for adult insomnia [35]. Similarly, in infants, diphenhy-
The current results suggest favorable prescribers’ per- dramine is no more effective for sleep than placebo [36].
ceptions about melatonin in terms of efficacy and side These medications are thought to induce tolerance [35],
effects, which may be slightly more prominent in younger and pose risks for overdose in children, either alone or in
generations of practitioners. This is aligned with emerg- combination with other over-the-counter allergy or cold
ing evidence, notably in Europe, that melatonin use in preparations.
children and adolescents has been increasing over time Practitioners in the present study generally avoided
[28]. Empirical data on the effects of melatonin in clini- benzodiazepines and non-benzodiazepine hypnotics,
cal pediatric population is scarce. An observational study both of which have worrisome adverse effects. While
in 100 children with disabilities receiving melatonin for there is regulatory approval for these drugs in adults, they
chronic sleep disturbances suggested sleep improve- are not approved for use in children and adolescents, and
ments in 80% of that sample, without major side effects respondents expressed several concerns about their use
or signs of tolerance [29]. Furthermore, a melatonin in depressed youth. In other words, Canadian child and
agonist administered about 2  h before bedtime induced adolescent psychiatrists were not more favorable to the
a phase advance in endogenous melatonin release, and use of medications which have regulatory approval for
improved both sleep and mood in adolescents and young adults. Whether this is a justifiable practice remains an
adults with depression [18]. Although melatonin is con- open question.
sidered safe [30], concerns persist about long-term safety Newer sleep promoting medications not yet approved
in children and adolescents, notably for the timing of in Canada are worth mentioning. For example, agomela-
puberty and potential interferences with the menstrual tine has approval for the treatment of major depressive
cycle [31, 32]. Further work is required to determine how disorder in Australia and the European Union, but not in
the potential side effects of melatonin may compare to Canada or the United States [37]. Ramelteon, tasimelt-
those of classical sleeping medications in children and eon, targeting the non-24-h-sleep–wake disorder, and
adolescents with depression. Also, the observation that suvorexant, an orexin receptor antagonist, are approved
melatonin is increasingly used to address sleep issues in in the USA but not in Canada. At low-dose, doxepin, a
youths stress the importance of tighter regulations since tricyclic antidepressant with potent antihistaminergic
inconsistencies in concentration and active ingredients in effects, is approved in Canada and the United States, but
melatonin tablets have been reported [33]. not for youths. Anticonvulsant drugs, such as gabapentin
In the current study, aside from melatonin, trazodone and pregabalin, are not officially approved for sleep but
and quetiapine were most commonly perceived as effec- may increase slow wave sleep and attenuate sleep dis-
tive. Although it was initially developed for the treatment turbance [38–40]. While clinical trials with these newer
of depression, trazodone has become the most commonly agents in children and adolescents are likely to remain
prescribed medication for insomnia [34]. These trends in limited, it will be important to collate clinical observa-
adult prescriptions, and concerns regarding the tolerance tions on their evolving off-label use in clinical settings.
and dependence resulting from hypnotics and benzodi- Several study limitations should be noted. We do not
azepines use, may have influenced child and adolescent know if the rather large proportion of our respond-
psychiatrists in their prescription habits. In Canada, que- ents holding a faculty position is representative of most
tiapine has been approved for schizophrenia, bipolar dis- Canadian child and adolescent psychiatrists, a factor
order and treatment-resistant major depressive disorder. likely to limit the generalizability of our findings. The
 Boafo et al. Child Adolesc Psychiatry Ment Health (2020) 14:10 Page 7 of 8

low response rate may limit generalizability, however it is Authors’ contributions

AB, SG, MS, KB, SS, LS, KM, and RR all contributed to the rationale and design
comparable to the response rate of other Canadian and of the project. They all contributed to searches of pertinent literature, data
American survey studies looking at prescribing habits of analysis, drafting and revising of the manuscript. They all gave final approval
sleep medications for pediatric patients [18, 24]. There for the person to be published, and agree to be accountable for all aspects of
the work. All authors read and approved the final manuscript.
was no open question or qualitative methods used as part
of this survey. Importantly, this study did not consider Funding
whether children and adolescents with sleep disturbance Financial support was provided by funds from the Psychiatry Associates at the
Children’s Hospital of Eastern Ontario (CHEO) in Ottawa, Ontario, Canada.
and depression share the views of their psychiatrists
with respect to the effectiveness or safety of these sleep Availability data and materials
promoting medications. Children, adolescents and their All the data and materials of the project are available upon request.
families often prefer nonpharmacological approaches Ethics approval and consent to participate
over pharmacotherapies for the management of sleep The Children’s Hospital of Eastern Ontario Research Ethics Board approved the
and depressive symptoms [41], but nonpharmacologi- study. The approval number is CHEO REB# 16/72X. Participants consented to
the study by completing the survey.
cal treatments of sleep disturbance were not addressed
in the survey. Such interventions, like cognitive behav- Consent for publications
ioural therapy for insomnia, have been found to be more Not applicable.
beneficial than frequently used medications in children, Competing interests
adolescents and adults [42]. Future surveys documenting The authors declare that they have no competing interests.
common clinical practices to address sleep problems in
Author details
pediatric depression should investigate potential barriers 1
 Mental Health Program, Children’s Hospital of Eastern Ontario, 401 Smyth
to nonpharmacological interventions (availability, cost, Road, Ottawa, ON KH 8L1, Canada. 2 Department of Psychiatry, University
and paucity of trained practitioners). of Ottawa, Ottawa, ON, Canada. 3 Sleep Research Unit, The Royal’s Institute
of Mental Health Research, Ottawa, ON, Canada. 4 School of Psychology,
University of Ottawa, Ottawa, ON, Canada.

Conclusion Received: 19 December 2019 Accepted: 20 February 2020

Melatonin and trazodone were the medications indicated
by the highest number of Canadian child and adolescent
psychiatrists surveyed as being effective and as being
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