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Sleep Disorder, Problems Associated With Other Disorders: Treatment & Medication
Updated: Feb 18, 2010
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
This section primarily reviews cognitive-behavioral treatments (CBT) effective in treating a broad range of childhood behavioral sleep problems. Treatment modalities can be adapted easily to the youth's developmental level. Furthermore, consider the role of sleep hygiene in all sleep problems. The effectiveness of CBT for childhood sleep disorders has been well demonstrated in controlled studies and clinical case reports. Specific interventions for sleep problems have gained the status of established evidence-based interventions. The issues that received the most attention pertain to settling problems and night awakenings in infants and toddlers. These topics have been extensively studied, with an impressive volume of well-controlled and informative clinical studies. Clinical research of all other sleep problems and in other age ranges is still very limited.
Family dynamics should be explored and redressed, as sleep patterns of parents and their adolescent children reveal similarities; strained and reciprocal parent-child interactions indicate that a mother’s poor sleep may directly affect parenting style. Accordingly, the adolescents’ psychological functioning and sleep are also affected.
Pharmacologic treatments of sleep disorders lack adequate and significant empirical data. Given the lack of data supporting pharmacological treatment, initially use behavioral and cognitive strategies in most cases. Because of the paucity of adequate empirical studies, pharmacotherapy data are limited to treatment in select sleep disorders.
- Limit-setting problems, bedtime resistance, and frequent nightly awakenings represent common problems encountered in pediatric practice. Cognitive-behavioral techniques use relatively straightforward and safe strategies for enhancing overall parenting effectiveness as well as ameliorating the aforementioned problems.
- Extinction technique: This technique involves the parents putting their child to bed at a designated time and ignoring the child's or infant's protests until an established time the next morning.
- Graduated extinction: Many parents may experience or perceive pure extinction as overly taxing or cruel; therefore, a graduated extinction technique may be used. This may include progressive time delays in responding to bedtime protests or refusals (ie, a checking technique), or it may include comforting the child for increasingly shorter intervals when checking on the child.
- Positive routine-stimulus control techniques: This technique involves developing a consistent, pleasurable, and calming nighttime routine, with pleasurable activities being halted if the child protests or throws a tantrum. The child is then put to bed.
- Scheduled awakenings: Parents awaken the child approximately 15 minutes prior to the child's typical nightly awakening times. The scheduled awakenings gradually are stopped or weaned.
- Nocturnal enuresis: History and physical examination usually are sufficient to rule out urological abnormality. Routine dipstick urinalysis, growth/height trajectory, and blood pressure are used to exclude other medical causes of enuresis. Children younger than 6 years should be managed with child and family reassurance that the enuresis is developmentally normal.
- Alarm clock method: An alarm is set before the most probable time of the event based on the trend of enuretic episodes. The alarm may be set for a predetermined time, such as 2-3 hours after usual onset of enuresis. Children eventually avoid wetting themselves before the alarm is triggered, unlike the bell and pad method. Longer treatment duration results in a higher success rate.
- Parent education: Parents need to know that sleep hygiene practices serve as prevention of enuresis. Fluid restriction, bedtime voiding, and parent awakening later are components of sleep hygiene (see Patient Education). The earlier the child begins practicing sleep hygiene, the better. Individual families may require creative combinations of the aforementioned interventions.
- Desmopressin and nocturnal enuresis: Desmopressin reduces nocturnal urine production, has better short-term results than the alarm method, is effective in 50-85% of individuals, and generally is well tolerated. Recidivism after discontinuation can present a problem.
- Imipramine and nocturnal enuresis: Imipramine is effective, but concern exists for potentially serious adverse effects. Imipramine dosing is 25-100 mg depending on the age and size of the patient. Risks involved in imipramine use often outweigh the benefits for the relatively benign problem. The use of imipramine requires ECG at baseline, with titration and dose increases and periodic monitoring. The clinician should monitor blood pressure and pulse rate and review cardiovascular system issues at each visit.
- Sleep-related fears and anxiety: Treatment for sleep-related fears and anxiety include relaxation training, guided imagery, positive self-talk, positive reinforcement for increasingly successful efforts, systematic desensitization, and gradual exposure to child-determined hierarchy of sleep-related fears or anxiety. The child progresses from envisioning less threatening fears to conquering in vivo actual feared objects or situations. Exposure-response prevention is combined with relaxation techniques and positive reinforcement for treatment gains.
- OSAS: Adenotonsillectomy is the primary treatment modality in children with OSAS. Positive airway pressure is needed in cases of continued postsurgical symptomatology. Continuous positive airway pressure (CPAP), variable pressure devices (eg, bilevel positive airway pressure [BiPAP]), and on-demand pressure when airflow is impeded (D-PAP) may be needed. Weight loss can be helpful for obese patients.
- PLMS: Focus cognitive and behavioral therapy on alleviating stress and promoting relaxation. Dopaminergic therapy may be necessary; however, only limited data on dopaminergic therapy in youths are available. Pergolide (withdrawn from US market March 29, 2007) is effective in treating ADHD or Tourette syndrome and comorbid sleep disorder. Caffeine restriction can be helpful. Low-dose Depakote has been shown to be effective in a small case series of adults.
- RLS: Focus cognitive and behavioral therapy on alleviating stress and promoting relaxation. Dopaminergic therapy may be necessary; however, limited data exist for treatment in youths. Pergolide (withdrawn from US market March 29, 2007) has been found to be effective in treating ADHD or Tourette syndrome and comorbid sleep disorder. Caffeine restriction may be helpful. Low-dose Depakote has been shown to be effective in small case series of adults.
- Insomnia in ADHD: A study by Blumer et al found that zolpidem failed to improve insomnia in children and adolescents with ADHD. The hypnotic efficacy of zolpidem was compared with that of placebo in children aged 6-17 years who experienced insomnia associated with ADHD. Patients were randomized to receive either zolpidem (dose of 0.25 mg/kg/d, not exceeding 10 mg/d) or placebo. After 4 weeks of treatment, baseline-adjusted mean change in latency to persistent sleep did not differ significantly between the zolpidem and placebo groups.28
- Circadian rhythm disorders
- Light therapy resets suprachiasmatic nuclei.
- Melatonin acts directly upon suprachiasmatic nuclei. The effect of light on phase shifts is opposite. Phase delay requires morning dosing of melatonin. Advanced sleep phase syndrome requires evening dosing.
- In manipulating the internal sleep-wake clock, gradually delaying sleep onset resynchronizes the internal clock. Delay sleep onset by 15-minute increments each night until desired sleep time is established.
Surgical Care
Adenotonsillectomy may be indicated for OSAS.
Consultations
Depending upon patient presentation, the following consultations may be necessary:
- Pulmonologist
- Developmental medicine specialist
- Neurologist
- Child psychologist, child psychiatrist, or developmental-behavioral pediatrician
- Sleep specialists (Multiple disciplines may have expertise, and the child may benefit from interdisciplinary evaluation and treatment planning.)
- Otolaryngologist
- Substance abuse evaluation
Diet
Weight loss is recommended for patients with obesity and OSAS.
Medication
Many of the medications described below are not approved by the Food and Drug Administration (FDA) for adolescents and children.
Vasopressin analogs
Desmopressin is a synthetic antidiuretic hormone with actions mimicking vasopressin. It is used for treating enuresis.
Desmopressin (DDAVP)
For use in primary nocturnal enuresis in children > 6 y. Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.
Adult
0.2-0.6 mg PO qhs
Pediatric
Nasal spray: 20 mcg (0.2 mL) intranasally qhs
Tablets: 0.1-0.4 mg PO qhs
Coadministration with demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects of desmopressin
Documented hypersensitivity; platelet-type von Willebrand disease; any potential for water intoxication
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Renal abnormalities; history of electrolyte imbalance
Dopamine agonists
Preliminary efficacious results for treatment using these agents have been noted in youths with RLS and PLMS. Findings are based on nonrandomized non – placebo-controlled study. Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. Do not abruptly stop pergolide. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.
Pergolide (Permax)
Pergolide withdrawn from US market. Not FDA-approved for RLS or PLMS. Potent and long-acting dopamine agonist. Reduces tonic stimulation of dopaminergic D-2 receptors located on intrastriatal cholinergic neurons.
Adult
0.05 mg PO hs for first 2 d initially; gradually increase by 0.05 mg/d q3d over next 12 d, followed by increments of 0.25 mg/d q3d until optimal therapeutic dosage is achieved, generally 0.25-0.5 mg is effective
Pediatric
Not established, limited data exist: 0.4-1 mg/d PO divided qid
Dopamine antagonists (eg, phenothiazines, butyrophenones, thioxanthenes, metoclopramide) may diminish effect; because pergolide mesylate is more than 90% bound to plasma proteins, exercise caution if pergolide is coadministered with other drugs known to affect protein binding
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause valvular heart disease (yearly echocardiograms recommended for patients on chronic therapy); inhibits secretion of prolactin; causes transient rise in serum concentrations of growth hormone and decrease in serum concentrations of luteinizing hormone; adverse effects include nausea, hypotension, hallucinations, and somnolence; use caution in patients who have been treated for cardiac dysrhythmias; may cause or exacerbate preexisting states of confusion and hallucinations or dyskinesia
Tricyclic antidepressants
These agents are used for treating narcolepsy and enuresis. Please note that scant data exist for use in childhood narcolepsy. Sudden death has been reported in 8 children, possibly related to use of imipramine and desipramine; findings have been inconclusive about the causes of these deaths. No FDA indication exists for use in children with narcolepsy and enuresis.
Imipramine (Tofranil)
Inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron. May be useful in pediatric ADHD as well as enuresis and possibly pediatric-onset narcolepsy.
Adult
Not established
Pediatric
10 mg PO qd initially and, if tolerated but not effective, increase dose to 25 mg PO qd; titrate upward slowly by 25 mg/wk to effectiveness or intolerable adverse effects
Increases toxicity of sympathomimetic agents (eg, isoproterenol, epinephrine) by potentiating effects; inhibits antihypertensive effects of clonidine
Documented hypersensitivity; narrow-angle glaucoma; acute recovery phase following myocardial infarction; concurrent use of MAOIs or fluoxetine or coadministration in the previous 2 wk (avoid)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Overdose may be lethal; may impair mental or physical abilities required for performance of potentially hazardous tasks; cardiovascular disease; conduction disturbances; seizure disorders; urinary retention; hyperthyroidism; patients receiving thyroid replacement; frequent ECG monitoring advised
Anticonvulsants
Valproic acid was efficacious in small case series for adults with RLS and PLMS.
Valproic acid (Depakene, Depakote)
It is likely that all forms of valproic acid have similar efficacy. The following preparations can be used: 250-mg tab, 125-mg sprinkle caps, or 250 mg/5-mL liquid (US preparations).
Adult
125-600 mg PO qhs when used in investigational studies for RLS and PLMS
Pediatric
Not established
Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein-binding sites (monitor coagulation test results); may increase zidovudine levels in HIV seropositive patients
Documented hypersensitivity; hepatic disease/dysfunction; history of thrombocytopenia due to valproic acid
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Thrombocytopenia and abnormal coagulation parameters have occurred; the risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and 135 mcg/mL in males; carefully monitor patients early in treatment; monitor periodically while the patient is stable; adolescent women may experience substantial weight gain and irregular menses and can develop polycystic ovaries; thrombocytopenic effect, particularly at higher doses and during intercurrent illnesses, may cause bruising/bleeding; mitochondrial syndromes may be worsened by valproic acid, thus use with extreme caution; do not use in pregnant adolescents or sexually active adolescents not taking adequate birth control
Hormones
These agents are used for treating circadian rhythm disturbances.
Melatonin
Used to treat circadian rhythm disturbances in blind patients without light perception.
Adult
1-10 mg PO qhs
Pediatric
Administer as in adults
Coadministration with other CNS depressants may result in excessive somnolence; fluvoxamine increases melatonin levels; may increase blood pressure and heart rate of patients on nifedipine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause dysphoria, headache, nausea, pruritus, and elevated alkaline phosphatase; caution with liver impairment, cardiovascular disease, neurologic disorders, or depression
Sedative/hypnotic agents
Studies for these drugs are limited to adults, and no FDA indications are approved for children younger than 18 years.
Eszopiclone (Lunesta)
Nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown, but believed to interact with GABA-receptor at binding domains close to, or allosterically coupled to, benzodiazepine receptors. Indicated for insomnia in adults to decrease sleep latency and improve sleep maintenance. Short half-life of 6 h. Higher doses (ie, 2 mg for elderly and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses are (ie, 1 mg for elderly and 2 mg for nonelderly adults) are suitable for difficulty in falling asleep.
Adult
Nonelderly adults: 2 mg PO hs; may increase to 3 mg PO hs prn
Elderly persons: 1 mg PO hs initially; not to exceed 2 mg PO hs
Severe hepatic impairment: Do not exceed 2 mg PO hs
Pediatric
<18 years: Not established
CYP3A4 and CYP2E1 substrate; potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, nelfinavir) increases AUC, Cmax, and t1/2 and therefore potential toxicity (decrease dose); potent CYP3A4 inducers (eg, rifampicin) increases clearance; coadministration with alcohol or other CNS depressants may increase effect and toxicity (decrease dose); coadministration with olanzapine may decrease DSST scores; sleep onset may be delayed if taken with or immediately after a high-fat or heavy meal
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause dysgeusia, headache, or cold-like symptoms; rare adverse effects associated with hypnotics include short-term amnesia, confusion, agitation, hallucinations, worsened depression, or suicidal thoughts; high doses (ie, 6-12 mg) produce euphoric effects similar to those of diazepam 20 mg; anxiety, abnormal dreams, nausea, and upset stomach may occur within 48 h after discontinuing; alertness may be affected the following day, use caution operating machinery or driving a car; caution with severe COPD or hepatic disease
Ramelteon (Rozerem)
Melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and be involved in maintaining circadian rhythm and normal sleep-wake cycle. Indicated for insomnia in adults characterized by difficulty with sleep onset.
Adult
8 mg PO qhs 30 min before bedtime on empty stomach
Pediatric
Not established
Major substrate of cytochrome P450 CYP1A2 and minor substrate of CYP2C and CYP3A4; strong CYP1A2 inhibitors (eg, fluvoxamine) increase AUC up to 190-fold and Cmax 70-fold; strong CYP inducers (eg, rifampin) decrease total exposure by mean of 80%; strong CYP3A4 inhibitors (eg, ketoconazole) and strong CYP2C9 inhibitors (eg, fluconazole) may increase serum levels
Documented hypersensitivity; strong cytochrome P450 CYP1A2 inhibitors (eg, fluvoxamine); severe hepatic impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May affect reproductive hormones in
adults (eg, decreased testosterone levels, increased prolactin levels), further study required to determine safety in prepubescent and pubescent children; caution with mild hepatic impairment; adverse effects leading to discontinuation in clinical trials included: dizziness, nausea, fatigue, headache, and worsening insomnia
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 Treatment & Medication: Sleep Disorder, Problems Associated With Other Disorders |
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References
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Further Reading
Keywords
associated problems in select sleep disturbances, dyssomnias, parasomnias, medical-psychiatric disorders, hypersomnia, insomnia, narcolepsy, obstructive sleep apnea syndrome, OSAS, periodic limb movements in sleep, PLMS, sleepwalking, somnambulism, bruxism, teeth grinding, grinding teeth, nightmares, night mares, sleep terrors, primary nocturnal enuresis, rhythmic movement disorders, confusional arousals, delayed sleep phase syndrome, DSPS, sleep disorders, sleep problems, rapid eye movement, REM, nonrapid eye movement, non-REM, NREM, circadian sleep-wake cycle, circadian rhythm
