New guidelines for diagnosis and treatment of insomnia.
ABSTRACT The Brazilian Sleep Association brought together specialists in sleep medicine, in order to develop new guidelines on the diagnosis and treatment of insomnias. The following subjects were discussed: concepts, clinical and psychosocial evaluations, recommendations for polysomnography, pharmacological treatment, behavioral and cognitive therapy, comorbidities and insomnia in children. Four levels of evidence were envisaged: standard, recommended, optional and not recommended. For diagnosing of insomnia, psychosocial and polysomnographic investigation were recommended. For non-pharmacological treatment, cognitive behavioral treatment was considered to be standard, while for pharmacological treatment, zolpidem was indicated as the standard drug because of its hypnotic profile, while zopiclone, trazodone and doxepin were recommended.
- SourceAvailable from: Anders Fernström[Show abstract] [Hide abstract]
ABSTRACT: This study aimed to evaluate effects of a non-pharmacological intervention on sleep, activity and fatigue in patients receiving peritoneal dialysis by the use of both actigraphy registration and self-assessed questionnaires. Insomnia is estimated to affect up to 60% of haemo- and peritoneal dialysis patients. It is associated with two common uremic symptoms, pruritus and restless legs syndrome. To our knowledge, no interventions have been evaluated by actigraphy. A prospective multiple baseline single-case experimental design. Two women and seven men with sleep problems, 48-77 years, treated with PD participated in a 17-week study from January 2009 to February 2011. Two interventions were separately implemented. First, a pressure-relieving mattress and second, a four week individual sleep hygiene and sleep scheduling intervention. The two interventions were evaluated both objectively by actigraphy and subjectively by questionnaires. A total of 315 sleep-wake cycles from nine individuals were evaluated. Three patients improved clinically significantly in five or more of the nine outcomes, i.e. sleep onset latency, nocturnal sleep duration, numbers and duration of napping, movement and fragmentation index, number of steps, metabolic equivalent unit, sleep efficiency and fatigue. The other six patients also showed improvements but to a lesser degree. Physical activity advice was the intervention that yielded most sleep improvements. This study illuminates the need for regular assessment of sleep and tiredness. It also demonstrates how a non-pharmacological treatment and self-management can be applied with renal supportive care to improve sleep quality. This study is a clinical example of a non-pharmacological intervention with supportive care and self-management. This model can improve health and reduce the pharmacological burden because hypnotics can be replaced by sleep hygiene self-care activities.Journal of Clinical Nursing 12/2012; 21(23-24):3402-17. · 1.32 Impact Factor
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ABSTRACT: The rate coefficient of the reaction H + O2 → OH + O was determined using tunable diode laser absorption of H2O near 2.5 μm behind reflected shock waves over the temperature range 1100–1530 K, at approximately 2 atm. Detailed kinetic analysis of the recorded H2O temporal profiles yielded the rate coefficient expression: k = (1.12 ± 0.08) × 1014 exp [(−7805 ± 90)/T] cm3 mol−1 s−1, with estimated uncertainties of ±4.6% at 1500 K and ±8.8% at 1100 K. Excellent agreement between this study and that of Masten et al. (1990) was found in the overlapping temperature range. By combining the results of these two studies, the reaction rate coefficient over the range 1100–3370 K was found to be described well by:Proceedings of the Combustion Institute 01/2011; 33(1):309-316. · 2.37 Impact Factor
Arq Neuropsiquiatr 2010;68(4):666-675
New guidelines for diagnosis
and treatment of insomnia
Luciano Ribeiro Pinto Jr.1, Rosana Cardoso Alves2, Eliazor Caixeta3,
John Araujo Fontenelle4, Andrea Bacellar5, Dalva Poyares1,
Flavio Aloe2, Geraldo Rizzo6, Gisele Minhoto7, Lia Rita Bittencourt1,
Luiz Ataide Jr.8, Márcia Assis9, Márcia Pradella-Hallinan1,
Maria Christina Ribeiro Pinto1, Raimundo Nonato D. Rodrigues10,
Rosa Hasan2, Ronaldo Fonseca11, Stella Tavares1
The Brazilian Sleep Association brought together specialists in sleep medicine, in order
to develop new guidelines on the diagnosis and treatment of insomnias. The following
subjects were discussed: concepts, clinical and psychosocial evaluations, recommendations
for polysomnography, pharmacological treatment, behavioral and cognitive therapy,
comorbidities and insomnia in children. Four levels of evidence were envisaged: standard,
recommended, optional and not recommended. For diagnosing of insomnia, psychosocial
and polysomnographic investigation were recommended. For non-pharmacological
treatment, cognitive behavioral treatment was considered to be standard, while for
pharmacological treatment, zolpidem was indicated as the standard drug because of its
hypnotic profile, while zopiclone, trazodone and doxepin were recommended.
Key words: insomnia, diagnosis of insomnia, treatment of insomnia, cognitive behavioral
Novas diretrizes no diagnóstico e tratamento das insônias
A Associação Brasileira de Sono reuniu especialistas em medicina do sono com o
objetivo de desenvolver novas diretrizes no diagnóstico e tratamento das insônias.
Nós consideramos quatro níveis de evidência: padrão, recomendado, opcional e não
recomendado. Os tópicos abordados foram: conceito, avaliação clínica e psicossocial,
indicação da polissonografia, tratamento farmacológico, terapia comportamental cognitiva,
comorbidades e insônia na infância. Para o diagnóstico da insônia, foi recomendada uma
avaliação psicossocial e a realização da polissonografia, enquanto que no que se refere
ao tratamento, foi estabelecido como padrão a indicação da terapia comportamental
cognitiva, e, quanto ao tratamento farmacológico, foi indicado o uso do zolpidem como
hipnótico padrão, e sendo recomendado o zopiclone, a trazodona e a doxepina.
Palavras-chave: insônia, diagnóstico da insônia, tratamento da insônia, terapia compor-
Luciano Ribeiro Pinto
Rua dos Franceses 498 / 204-A
01329-010 São Paulo SP - Brasil
Received 2 March 2010
Received in final form 11 March 2010
Accepted 18 March 2010
Brazilian Sleep Association: 1Federal University, São Paulo SP, Brazil; 2University, São Paulo SP, Brazil; 3School of Medicine
Science, MG, Brazil; 4Federal University, RN, Brazil; 5Carlos Bacelar Clinic, RJ, Brazil; 6Moinhos de Vento Hospital, Porto Alegre
RS, Brazil; 7Catolic University, Curitiba PR, Brazil; 8University, PE, Brazil; 9São Lucas Hospital, Curitiba PR, Brazil; 10University,
Brasília DF, Brazil; 11State University, São Paulo SP, Brazil.
Even today, insomnia remains a clinical
entity that is difficult to diagnose and com-
plex to treat, demanding an approach with
appropriate strategy and planning. Insom-
nia, as a symptom, syndrome or disease,
has serious social and professional conse-
quences, affecting daily activities and ren-
dering individuals incapable of performing
their tasks. It therefore generates a high
cost for society.
In November 2008, the Brazilian Sleep
Society brought together doctors who
Arq Neuropsiquiatr 2010;68(4)
Pinto Jr. et al.
specialize in sleep medicine, in São Paulo. The meet-
ing aimed to provide new guidelines for diagnosing and
treating insomnia. During this meeting, the following
subjects were considered: concepts, clinical and psycho-
social evaluations, recommendations for polysomnog-
raphy, pharmacological treatment, behavioral and cog-
nitive therapy, comorbidities and insomnia in children.
Based on searches in the literature for articles, reviews
and meta-analyses, five levels of evidence were put for-
ward as recommendations for managing insomnia:
Level I - Randomized trials with low false-positive (al-
pha) and low false-negative (beta) errors (high power); ev-
idence obtained from meta-analyses on randomized con-
trolled trials; Level II - Randomized trials with high false-
positive (alpha) and (or) high false-negative (beta) errors
(low power); evidence obtained from at least one ran-
domized controlled trial; Level III - Nonrandomized con-
current cohort comparisons between patients with and
without receiving a concomitant nutritional intervention;
evidence obtained from at least one well-designed, con-
trolled study, without randomization; Level IV - Nonran-
domized historical cohort comparisons between current
patients who received a nutritional intervention, and for-
mer patients (from the same institution or from the lit-
erature) who did not; Level V - Case series without con-
trols; evidence obtained from expert committee reports
or opinions and/or clinical experiences from respected
authorities. Based on these five levels of evidence, the rec-
ommendations for interventions were considered to be:
standard (levels I and II); recommended (levels III and
IV), optional (level V) and not recommended, when no
level of evidence existed1,2.
Insomnia is defined as a disorder that is character-
ized by difficulty in falling asleep or maintaining sleep.
Furthermore, insomnia is also related to dissatisfaction
with the quality of sleep, thus resulting in daily physical
and emotional symptoms that have an impact on social
and cognitive performance3.
According to the latest classification of sleep disorders
(2005), insomnia is divided into the following forms: acute
insomnia, psychophysiological insomnia, paradoxical in-
somnia, idiopathic insomnia, insomnia associated with
mental disorders, insomnia associated with systemic dis-
eases and insomnia associated with inadequate habits4-6.
Acute insomnia, transitory insomnia
or adjustment insomnia
The essential element for this diagnosis is the pres-
ence of symptoms of acute insomnia caused by a trigger-
ing causal factor that is clearly identified in an individu-
al who previously had a normal sleeping pattern, without
insomnia complaints. This clinical condition lasts no lon-
ger than one month4.
Primary chronic insomnia
In the etiopathogenesis of primary insomnia, three
points should be considered: predisposing (genetic and
constitutional), precipitating and perpetuating factors.
Predisposing factors depend on hyperactivity of the
awakening system (stress response mechanisms), hy-
peractivity of the hypothalamic-pituitary-adrenal axis,
anxiety and depression, abnormalities in the mecha-
nisms of sleep-wakefulness homeostasis, abnormali-
ties in the circadian rhythm (circadian sleep-wakeful-
ness control) and abnormalities of the intrinsic mech-
anisms of sleep-wakefulness control7-11. The precipitat-
ing and perpetuating factors depend on psychosocial fac-
tors, behavioral changes and cognitive characteristics.
Primary insomnia can be divided in three subtypes,
namely psychophysiological, idiopathic and paradoxi-
cal4. Psychophysiological insomnia occurs concomitant-
ly with a cognitive hyperalert state that is characterized
by anxiety related to the act of sleeping and the presence
of neurocognitive symptoms such as fatigue and irrita-
bility. Idiopathic insomnia starts before puberty and per-
sists throughout adulthood, and a family history of in-
somnia is often present. In paradoxical insomnia, sub-
jective complaints of poor quality sleep can be observed,
despite the lack of objective sleep abnormalities on poly-
somnography. This subtype of insomnia is related to sleep
 Mental disorder - The essential factor of this type
of insomnia is the temporal and causal relationship with
an underlying mental disorder. Mood disorders such as
depression, dysthymia, cyclothymia, bipolar disorder,
anxiety, schizophrenia and somatoform disorders are ex-
amples of mental disorders associated with this type of
 Inadequate sleep hygiene - This is related to hab-
its that are inappropriate for good quality of sleep, for ex-
ample psychologically stressful activities, consumption
of caffeine, nicotine, alcohol and heavy meals, vigorous
physical activity close to bed time, inconstant time for
going to sleeping and waking up, long naps or naps near
the main time for sleeping4.
 Medical condition - This sleep disorder is related
to particular medical conditions, for example painful syn-
dromes, infections, metabolic diseases, hyperthyroidism
and neurological diseases4.
 Use of substances or medication - This sleep disor-
der is related to the use of a drug or substance such as al-
Arq Neuropsiquiatr 2010;68(4)
Pinto Jr. et al.
cohol, stimulants (amphetamine and derivatives) or an-
Obstructive sleep apnea
In 1973, Guilleminault et al described the association
between insomnia and obstructive sleep apnea, and called
it “sleep-insomnia apnea syndrome”19. The relationship
between these two common sleep disorders is complex
and unclear. There is a higher incidence of breathing dis-
orders in insomniac patients than there is in the gener-
al population20,21. The severity of insomnia symptoms is
strongly correlated with the severity of apnea, thereby
characterizing comorbidity. Lichstein et al demonstrat-
ed that high proportions of individuals, particularly the
elderly, present this combined condition of undiagnosed
sleep apnea and insomnia22. Therefore, polysomnography
(PSG) can help identify a substantial number of breathing
disorders that are associated with insomnia23,24.
Women at the premenopausal and menopausal peri-
ods are more likely to develop sleep complaints and disor-
ders than are women of a fertile age. Conjugated hormon-
al therapy (estrogen and progesterone) has been shown
to efficiently improve general sleep complaints, as well as
insomnia and OSAS25. Benzodiazepine drugs are asso-
ciated with reductions in wakefulness, reductions in the
muscle tonus of airways and decreases in the ventilatory
response to hypoxemia. Therefore, these drugs are con-
sidered to be inappropriate for treating these comorbidi-
ties. The use of CPAP or oral devices also interferes neg-
atively in the quality of sleep, particularly during the ad-
Patients with fibromyalgia present persistent tired-
ness and physical fatigue, associated with non-restoring
sleep and diffuse muscle pain. Usually, these patients have
the perception of a sleep disorder associated with fatigue.
Pharmacological treatment mainly consists of tricycles
antidepressants and cyclobenzaprine26-32.
Circadian rhythm disorders
The delayed sleep phase syndrome is a circadian
rhythm disorder, characterized by delays in falling asleep
and in waking in the morning. This condition usual-
ly starts during childhood and adolescence, and is sel-
dom misinterpreted as insomnia, particularly idiopath-
Restless legs syndrome and
periodic movements of limbs
The restless legs syndrome is characterized by senso-
ry disorders that mainly affect the lower limbs, particu-
larly before falling sleep, thus leading to difficulty in fall-
ing asleep. Periodic movements of limbs usually accom-
pany the restless legs syndrome during sleep, leading to
a fragmented sleeping pattern, which affects the quality
of sleep. Periodic movements of the lower limbs can oc-
cur during sleep, independently of the existence of rest-
less legs syndrome. In these cases, the repercussions on
the sleep profile, with insomnia or daytime hypersomno-
lence, must be analyzed one by one, in each case43.
When considering the etiopathogenesis of insomnia,
it is important to highlight that insomnia may be of bi-
ological, environmental, behavioral or psychological na-
ture. Likewise, the factors causing and perpetuating in-
somnia are interrelated with social, professional and fam-
ily factors. Therefore, insomnia evaluations need to be
broad-based, covering the patients’ medical, psychologi-
cal and social characteristics.
Medical evaluation (standard)
Evaluations on insomniac patients should begin by
taking a rigorous and detailed medical history in which
the history of symptoms is recorded, including the start
of insomnia and its progression to a chronic condition,
along with treatments already used and repercussions
of the abnormal sleeping pattern during the day, such as
somnolence, tiredness, fatigue and reduction of attention,
concentration and memory44.
Nighttime habits that should be recorded include: bed-
time, activities in bed, turning off lights, time to fall asleep,
time to waking up in the morning, time to getting up, sleep
quality, number of awakenings, time spent awake dur-
ing the night and reports of snoring and leg movements.
Day habits that should be recorded include: meal-
times, work and study periods, daytime naps, physical
activity, smoking habit, alcohol intake, use of drugs and
Bedroom conditions that should be recorded include:
condition of the bed, mattress and pillows, number of
people who sleep in the same bed, luminosity, noise, tem-
perature and presence of a TV, computer or audio equip-
ment in the bedroom.
Psychosocial evaluation (recommended)
This has the aim of investigating, in greater detail, the
main precipitating and perpetuating factors of insomnia.
A psychosocial evaluation must be carried out, taking
into account the systemic focus, i.e. the insomnia symp-
toms are analyzed within the context of patients lives, and
what these symptoms allow or cover45-48.
Subsidiary examinations (recommended)
It is recommended that every insomniac patient
should undergo complementary examinations when there
is a suspicion of any systemic disease.
The use of a sleep diary, as well as other question-
naires, is fundamental to cognitive-behavioral therapy.
Arq Neuropsiquiatr 2010;68(4)
Pinto Jr. et al.
In order to investigate comorbidities such as obstruc-
tive sleep apnea, and for objective evaluation of sleep in
cases of diagnosing inadequate perception, polysomnog-
raphy is recommended as an auxiliary method for diag-
nosing of insomnia, whenever possible49-52.
Treatment of primary insomnia
Cognitive-behavioral therapy (standard)
Today, cognitive-behavioral therapy (CBT) is a stan-
dard treatment for primary insomnia. It must not be
used alone but, rather, in association with pharmaco-
logical therapy53-58. CBT presents an advantage over
pharmacological treatment: the low risk of side ef-
fects and the long-term maintenance of sleep pattern
improvement. CBT has a limited and defined peri-
od of use, from four to eight sessions. It is a focal and
direct type of therapy, in which patients play an ac-
tive role and are co-responsible for their treatment.
It can be undertaken individually or in groups59-62.
The interventions are educational, behavioral and cog-
nitive, and their theoretical basis is the behavioral mod-
el of insomnia proposed by Spielman. According to this
model, three main factors can cause insomnia: predis-
posing, precipitating and perpetuating factors. The main
CBT targets are the precipitating and perpetuating fac-
tors. The main behavioral and cognitive techniques are
sleep hygiene, stimulus-control therapy, therapy of bed-
time and sleeping time restriction, relaxation techniques,
cognitive restructuring, paradoxical intention and cogni-
tive therapy in sleep misperception disorders63-67.
 Sleep hygiene: This is a psychoeducational inter-
vention containing basic information on sleep habits and
hygiene. It includes instructions for establishing regular
sleeping times; going to bed only when feeling sleepy
and not using the bed as a means of trying to sleep; not
spending the day worrying about sleeping time; having
control over time; avoiding the use of stimulants (cof-
fee, cigarettes, drugs, black tea, Coca-Cola and choco-
late); avoiding alcohol consumption before sleeping; and
avoiding high liquid consumption before sleeping. It in-
cludes suggestions for dinner (light foods) not less than
two hours before going to sleep, and for regular physi-
cal activity, preferably in the mornings. It evaluates the
bedroom conditions: comfort, temperature, noise, and
stresses the importance of having a bedroom that is si-
lent, aired, clean and organized.
 Stimulus-control therapy: This aims towards edu-
cating insomniac patients on how to establish a more ap-
propriate sleep-wakefulness rhythm and limit the time
awake and the behavior allowed in the bedroom/bed. The
main instructions for patients include the following items:
to go to bed only when feeling sleepy; avoid any behav-
ior other than sleep or sex in the bedroom/bed; if feeling
incapable of sleeping, the patient should get up from bed
and go to another place to do some relaxing activity in
an environment with little light, and only go back to bed
when feeling somnolence again; to keep to a fixed time
for waking up, seven days per week, independently of the
amount of sleep obtained; not to nap or to lie down dur-
ing the day, to remove the TV, stereo and computer from
the bedroom; not to eat, read, work, watch TV or use a
computer in the bedroom/bed.
 Therapy of bedtime and sleeping time restriction:
The aim of this therapy is to consolidate sleep through
restricting the time that patients spend in bed to the av-
erage time they spend sleeping (i.e. the number of hours
that they really spend sleeping), based on the information
in the sleep diary. This technique creates a mild state of
sleep deprivation that may cause daytime somnolence.
However, at the same time, it provides sleep consolida-
tion, thus making it easier to fall asleep, improving sleep
efficiency and decreasing latency and variability between
nights. It is not recommended to have less than four to
five hours of sleep, and the necessary adjustments must
be made in relation to time spent in bed, according to pa-
tients’ responses to the proposed treatment. If patients
reach 90% sleep efficiency, 15 minutes are added to the
time allowed in bed and, if the efficiency is less than 85%,
15 minutes are taken away.
 Relaxation techniques: The aim of teaching relax-
ation techniques is to show patients how tense and hy-
pervigilant they are during both day and night. Progres-
sive relaxation is the treatment for insomnia that has been
studied most. Patients are guided to tension and relax
the major muscle groups sequentially, while observing the
sensation of tension and relaxation.
 Cognitive restructuring: This is mainly based on
cognitive symptoms that can cause or perpetuate insom-
nia. Cognitive restructuring works on concerns, thoughts,
false attitudes, irrational beliefs about sleep and amplifi-
cation of its consequences, false ideas about the causes
of insomnia and disbelief about sleep induction practic-
es and about their own capacity to sleep. The idea is to
make patients abandon the symptoms of insomnia, by re-
minding them that the way in which events are thought
about or judged determines the way that individuals feel
 Paradoxical intention: This technique reduces the
anticipatory anxiety associated with the fear of trying
to fall sleep and not being capable of doing so, since in-
somniacs usually believe that they have lost their natu-
ral capacity to fall asleep. Patients are instructed to go to
bed and stay awake and try not to sleep; this makes them
more relaxed and not under obligation to fall asleep. They
consequently fall asleep faster.
Arq Neuropsiquiatr 2010;68(4)
Pinto Jr. et al.
 Cognitive therapy for sleep misperception disorders:
This therapy works on the relationship between patients’
subjective perceptions of total sleeping time and the to-
tal sleeping time obtained through PSG. The intention of
this approach is to give patients objective data on sleep
efficiency obtained through PSG and make them com-
prehend that they are sleeping for longer than they think.
This technique also makes them more relaxed regarding
the quantity of sleep they consider necessary, and it en-
ables them to fall asleep more easily when this new real-
ity is acquired51-52.
Pharmacological treatment consists of the use of hyp-
notic drugs that induce sleep, mainly because they act on
the main inhibitory system of the central nervous system,
the GABA system. Additionally, substances presenting
sedative effects, such as antidepressants, may be used.
More recently, medications that act on melatoninergic
receptors have been considered promising as drugs for
GABA-A receptor-selective agonist hypnotics
 Zolpidem (standard): This is the hypnotic drug
used for treating insomnia. Zolpidem is an imidazopyri-
dine that was developed in 1980 and has been used since
1990. It was the first selective α1 agonist. It is rapidly ab-
sorbed (in approximately one hour) and presents a short
half-life of 2.5 hours. Its bioavailability ranges from 65%
to 70%. Plasma concentration peaks occur 1.5 hours after
drug intake. The therapeutic doses range from 5 to 10 mg,
and the drug is metabolized in the liver and eliminated by
the kidneys. In older people, and in cases of liver or kidney
failure, the recommended dose is 5 mg73. Although the use
of sleep inductors for treating chronic insomnia is only
recommended for one month, clinic trials have suggested
that zolpidem remains effective and safe for a prolonged
period of use, i.e. more than 35 days, in a 10 mg doses74,75.
The use of zolpidem reduces the cyclic alternating pat-
tern types A1 and A2, even when in intermittent use76,77.
Slow-release zolpidem (zolpidem MR, still not avail-
able in Brazil) is a new formulation used for patients with
difficulty in maintaining their sleep. This formulation
comprises pills with immediate release and pills for pro-
longed release, which maintains plasma concentrations for
three to six hours after intake78,79. Zolpidem can also be
used intermittently over the long term, in accordance with
patient needs, without rebound insomnia appearing80-82.
 Zopiclone (recommended): This is a hypnotic drug
that is recommended for treating insomnia. Zopiclone is
a cyclopyrrolone that differs from zolpidem because of
its longer half-life (5.3 hours) and its action on receptors
containing the subunits α1 and α2. The recommended
dose is 3.7 to 7.5 mg. A few side effects after withdrawal
have been described; however, the residual effects on the
following day may be attributed to its long half-life83.
 Zaleplon (recommended) - not available: This is
a pyrazolopyrimidine that links to the α1 receptor, thus
making the drug a hypnotic agent that can be recom-
mended for treating insomnia. The recommended dose is
10 mg and its half-life is approximately one hour. Because
of these characteristics, zaleplon is indicated for sleep in-
duction, while showing little effect on sleep maintenance.
Zaleplon has already been in the Brazilian market, but it
was withdrawn, which limits its use in this country 84.
 Eszopiclone (recommended) - not available: This
is a zopiclone isomer of cyclopyrrolone that is recom-
mended for treating insomnia. Eszopiclone is rapidly ab-
sorbed and presents a relatively long half-life. The dose
must be individualized, but ranges from 1 to 3 mg before
going to bed85-87.
 Indiplon (recommended) - not available: This is a
pyrazolopyrimidine with similarities to zolpidem, zopi-
clone and zaleplon that is selective for receptors that con-
tain a subunit α 1. It is a hypnotic drug recommended for
treating insomnia. This drug has a formulation for imme-
diate release (indiplon IR), which is indicated for initial
insomnia, and a controlled formulation (indiplon MR),
which lasts six to eight hours and is indicated for patients
with complaints regarding sleep maintenance. The rec-
ommended dose ranges from 15 to 30 mg, taken just be-
fore going to bed88.
Sedative antidepressants (tricyclic, trazodone, doxe-
pin and mirtazapine) are alternatives for pharmacologi-
cal treatment of insomnia. However, there are no double-
blind randomized studies proving the efficacy and safe-
ty of these agents. Some tricyclic antidepressants such as
amitriptyline improve sleep continuity and efficiency and
produce sedation during the day89.
 Trazodone (recommended): Trazodone seems to be
the second most commonly prescribed agent for treating
insomnia. It belongs to the pharmacological group of se-
rotonin reuptake inhibitors, and has antagonist action on
the adrenergic receptors α 1, 5-HT1A and 5-HT2. Tra-
zodone slightly suppresses REM sleep and improves sleep
continuity. The recommended dose is 50 mg/day90.
 Doxepin (recommended): This is a tricyclic antide-
pressant with antagonist effect on histamine H1/H2 recep-
tors. It has been shown to be efficient if used in small doses
(1 to 6 mg/night), for treating insomnia. It does not cause
clinically significant residual or anti-cholinergic effects91.
 Mirtazapine (optional): This is an atypical anti-
depressant. Its mechanism of action depends on the in-
creased noradrenergic activity provided by the antago-
nist effect of the drug on alpha-2a adrenergic receptors,
and nonspecific blockage of serotonergic reuptake. Mir-
Arq Neuropsiquiatr 2010;68(4)
Pinto Jr. et al.
tazapine is a postsynaptic antagonist (blocker) of 5TH2A
and 5TH 2C and 5-HT3 with sedative and anxiolytic ef-
fects. Its histaminic H1 anti-receptor activity explains the
strong sedative effect, and this is the antidepressant with
the greatest sedative effect among the currently available
drugs. The recommended doses range from 7 to 30 mg92.
 Amitriptyline (optional): This presents significant
sedative effects due to its anticholinergic, anti-histamin-
ic and anti-alpha1 profile, and also due to the blockage
of 5HT2A and 5HT2C receptors. The sedative effects are
immediate, preceding the antidepressant effects, and de-
crease after a few weeks of treatment. The recommend-
ed dose ranges from 12.5 to 50 mg.
 Mianserin (optional): This is an atypical antide-
pressant with sedative effect that occurs through anti-
histaminic 1 and 5HT2A/2C receptor antagonistic effects.
There are no long-term studies proving the efficacy and
safety of mianserin for treating insomnia.
Valerian (valepotriates) may be an option for treat-
ing insomnias and is used as an auxiliary medication
when discontinuing benzodiazepine among chronic us-
ers. Some studies have reported that its mechanism of
action is related to GABA. Valerian may act during sleep
through other mechanisms, through MT1 and MT2 re-
ceptors (melatonin) and through the A1 adenosinergic re-
ceptor and some subtypes of 5-HT receptors93.
Benzodiazepines (BZDs) link nonspecifically to the al-
pha-1 and alpha-2 subunits of the GABA-A postsynap-
tic receptor and to any subunit of the gamma type. BZDs
increase the affinity of the GABA-A postsynaptic recep-
tor with endogenous GABA, and increase the intensi-
ty and duration of the inhibitory effects through boost-
ing chloride channels. The link to the subunit alpha-1 is
responsible for the hypnotic and cognitive effects of this
drug, while the link to the subunit alpha-2 is responsible
for the anxiolytic, anti-convulsion and muscle-relaxing
effects. Withdrawal of BZDs may bring back the insom-
nia or cause rebound insomnia in patients, with worse
symptoms than those presented before treatment. The
presence of anxiety and the intensity of insomnia depend
on patients’ psychological profiles. Gradual and slow dis-
continuation of BZDs, with technical support, is recom-
mended. The abstinence symptoms when discontinuing
BZDs depend on a variety of factors. Many chronic users
will be able to discontinue treatment successfully, provid-
ed that it is done with an appropriate technique94-95.
Medication abuse often occurs among chronic users.
Tolerance reflecting the progressive increase of BZD dos-
es also depends on several factors. However, there are pa-
tients who do not develop tolerance after using BZDs for
a long time. There are studies demonstrating the existence
of a correlation between prolonged use of BZDs and in-
creased risk of death. Amplification of obstructive ventila-
tory disorders during sleep, sedation, suppression of self-
care, falls, confusion, amnesia and other possible drug-
related symptoms may explain the increased mortality.
BZDs are not indicated for individuals with drug addic-
tion and alcohol abuse. Special care is necessary with el-
derly individuals, patients with kidney, liver and lung dys-
functions, and patients with psychiatric problems. BZDs
may worsen the ventilatory disorders during sleep and are
not indicated during pregnancy, or for individuals whose
work may require prompt waking up and quick decision-
Among BZDs, clonazepam (optional), midazolam (op-
tional) and estazolam (optional) can be used. The other
BZDs are not recommended.
Melatonin receptor agonists (optional)
 Ramelteon: This is a new hypnotic drug that has
been approved for treating chronic insomnia. It is an ag-
onist with high selectivity for melatonin MT1 and MT2
receptors96. The 8 mg recommended dose is rapidly ab-
sorbed (0.75-0.94 hour) and presents a half-life of 1.3
hours. Due to its short half-life, Ramelteon is indicated
for treating initial insomnia97-99. It is not efficient in main-
taining sleep. Ramelteon is safe with regard to cognitive
effects on the following day, and has not been shown to
cause rebound insomnia when discontinued after chron-
ic use. It has not shown any potential for abusive use or
 Agomelatine: This is an antidepressant with agonist
action on melatonin receptors 1 and 2, and antagonist ef-
fect on serotoninergic 5-HT2C receptors. Because of its
melatoninergic agonist effect, agomelatine may be a po-
tential regulator of the circadian rhythm of depressed pa-
tients, thus leading to an added contribution for improv-
ing depression. Use of this medication at a dose of 25 to
50 mg has been shown to improve sleep quality, with re-
duced sleep latency, reduced awakening and increased
Other pharmacological and new perspectives
Antihistamines are optional, while antipsychotics are
New GABA agonists, like tiagabine and gaboxadol,
are still not available in Brazil and are not recommend-
ed. These drugs are inhibitors of GABA reuptake, and are
among the new perspectives for treating insomnia105-110.
Insomnia during childhood
Insomnia during childhood is divided into behavior-
al insomnia, psychophysiological insomnia, insomnia
in special populations, insomnia associated with clini-
cal conditions and insomnia associated with the use of
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Pinto Jr. et al.
medications. The most common clinical causes of insom-
nia during childhood are pain or cramps, recurrent oti-
tis, reflux, medications (stimulants or corticoids), night
asthma attacks and airway obstructions.111 The main type
of insomnia in children is behavioral insomnia, but this
is an exclusion diagnosis. During the first approach to-
wards the child, the clinical causes of insomnia must al-
ways be eliminated.
 Behavioral insomnia during childhood: This oc-
curs in 10 to 30% of preschool children. The Internation-
al Classification of Sleep Disorders (ICSD-2005) defines
children’s difficulty in falling asleep and/or maintaining
sleep as the essential characteristic of behavioral insom-
nia. These problems are associated with certain attitudes
among children or their parents, and they can be classi-
fied into two types: association disorder and lack-of-lim-
 Association disorder: There are certain conditions
associated with the start of sleep that are necessary for
children to fall asleep and for them to go back to bed af-
ter each awakening during the night. Positive associations
are conditions that children can provide for themselves
(pacifiers/dummies or teddy bears), while negative associ-
ations need assistance from someone else (baby bottles or
rocking). The negative associations also include external
stimuli (television or toys) or different situations (parents’
bed or a car ride). When the condition associated with
sleep is present, the child falls asleep rapidly. If the con-
dition associated with sleep is not present, the child pres-
ents frequent and long-duration nighttime awakenings.
The diagnostic criteria consist of findings that falling
asleep is a slow process that requires special conditions,
and that associations with falling asleep are problematic
and require much effort. When association elements are
absent, the start of sleep is significantly delayed or sleep is
fragmented. Nighttime awakening requires intervention
so that these children can fall asleep again.
 Lack-of-limit disorder: This is presented as a refus-
al or delay in going to bed at the established time. On the
other hand, delaying the time for going to sleep might in-
clude several requests (feeling thirsty, needing the bath-
room or asking for one more goodnight kiss) or addi-
tional activities (watching TV or reading one more sto-
ry). Once these children fall asleep, their sleep quality is
normal and they tend to have few awakenings. Howev-
er, children with lack-of-limit disorder normally have a
shorter sleeping time (30 to 60 minutes).
The diagnostic criteria consist of difficulty in falling
asleep or maintaining sleep; postponing or refusing to go
to bed at the appropriate time or refusing to go back to
bed after nighttime awakening; inability of the parents to
establish appropriate sleep behavior for the child; lack of
explanation for the sleep disorder in terms of other sleep
disorders, clinical conditions, mental or neurological dis-
eases, or use of medications.
 Insomnia associated with neurological and psychi-
atric conditions: Most syndromes with central nervous
system dysfunction present some kind of sleep abnor-
mality in their clinical presentation.
Medical evaluation (standard) - The main questions
in evaluating sleep disorders in pediatric cases include
duration of sleep, sleep routines, events associated with
sleep, daily behavior, humor and cognitive function. It is
also essential to find out about significant events in the
child’s life, such as parents’ divorce, changes of school or
moving house, or events involving siblings. A sleep diary
must be kept over a one or two-week period, and this is
always useful for finding out about sleeping patterns and
for following them over time. Parents are asked to write
details about what time the child went to bed, how long
the child took to fall asleep, the frequency and duration
of nighttime awakening, the time and duration of daily
naps, the time of waking up in the morning and the total
duration of sleep113.
Polysomnography (optional): Polysomnographic testing
and actigraphy are optional in diagnosing and treating in-
somnia in children. They are indicated only when necessary.
Children with insufficient duration of sleep present fa-
tigue and irritability. Parents may present negative feel-
ings towards their children and, in order to avoid frustra-
tions during sleeping times, they may postpone the sleep
routine, which delays the start of sleep even more and
prolongs the cycle of addiction.
 Behavioral approach (standard): Time for going
to sleep: The appropriate time for a child to go to sleep,
from infancy to preschool age, should be between 7:00
and 8:30 pm. When bedtime is later than this, children
get very tired, irritated and have difficulty in sleeping. The
time for going to sleep should not vary between weekdays
and weekends. Daytime naps are essential for the child.
The need for daytime naps tends to disappear between
the ages of three and six years114.
Bedtime routine: Establishing a routine is very impor-
tant for children’s lives. The bedtime routine can be start-
ed at three months of age, through establishing a con-
stant time for going to sleep. Any electronic equipment
near the child must be turned off before starting the rit-
ual for going to sleep.
Falling asleep independently: Children with insomnia
are incapable of falling asleep without their parents’ in-
tervention, such as rocking or feeding. Children must be
put in the cradle or go to bed when they are sleepy, but
still awake, and then they must fall asleep independently.
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Pinto Jr. et al.
There are several methods that help children fall asleep by
themselves, for example, “extinction” alone, gradual “ex-
tinction”, positive routines, brief visits and weaning chil-
dren from their parents’ presence115.
“Extinction” alone consists of leaving the child cry un-
til falling sleep. “Extinction” is based in the theory that be-
havior that is reinforced increases in frequency, while be-
havior that is ignored will disappear with time. If parents
are regular and do not attend their child’s calls, in gener-
al, the child will be able to sleep alone after three to five
nights. Gradual extinction is an alternative for parents
who do not want to use extinction alone. This method
consists of putting the sleepy, but awake, child in the cra-
dle and then ignoring the calls or crying for gradually in-
creasing periods. When observing the child at night, the
visit must be short and uniform, without lights and with-
out speaking loudly or touching the child.
The gradual reduction of the mother’s presence in-
cludes an initial phase in which physical contact is re-
duced at bedtime. Mothers who feed their children at
bedtime must do this activity earlier in another room and
only rock the child to sleep. After achieved success with
this strategy, the child must be put in the cradle and the
mother must caress the child’s head or arm until the child
falls asleep. In the second step, the mother’s presence in
the bedroom must be reduced. The third step consists of
increasing the time between each visit. Positive routines
aim to create a pleasant and positive environment not
only for the child but also for the parents.
 Pharmacological treatment (optional): Pharmaco-
logical treatment must be considered as the last option.
Most medications prescribed for insomnia among adults
are not recommended for children. However, in specific
cases, generally when there is an underlying neurologi-
cal or psychiatric disease, BDZs can be used (clonazepam,
clobazam, midazolam or diazepam), as well as zolpidem,
zopiclone, chloral hydrate, levomepromazine, promethaz-
ine, carbamazepine, clonidine, risperidone and melatonin,
always considering the age of the child and the risk/ben-
efit associated with the use of these drugs116.
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