eMedicine Specialties > Psychiatry > Psychosomatic

Primary Hypersomnia

Adrian Preda, MD, Health Sciences Associate Professor of Psychiatry and Human Behavior, University of California Irvine School of Medicine

Updated: Nov 3, 2009

Introduction

Background

In 1966, William Dement proposed that patients with excessive daytime sleepiness (EDS) but without cataplexy, sleep paralysis, or sleep-onset rapid eye movement (REM) should not be considered narcoleptic.¹ In 1972, Roth et al described a type of hypersomnia with sleep drunkenness that consists of difficulty coming to complete wakefulness, confusion, disorientation, poor motor coordination, and slowness accompanied by deep and prolonged sleep.² The abrupt sleep attacks seen in classic narcolepsy are not present in this disorder.

According to the International Classification of Sleep Disorders (ICSD), idiopathic (primary) hypersomnia is defined as a disorder of presumed central nervous system (CNS) cause that is associated with excessive sleepiness consisting of prolonged sleep episodes of non–rapid eye movement (NREM) sleep.³  

While both the DSM and ICSD define 2 types of idiopathic/primary hypersomnia based on the sleep time duration (ie, with or without long sleep), the presentation is often heterogeneous.⁵

In the literature, 3 possible subgroups of idiopathic CNS hypersomnia have been suggested, as follows:

• Subgroup I: These patients have a positive family history, and associated clinical symptoms suggest dysfunction of the autonomic nervous system. These symptoms include headache, syncope, orthostatic hypotension, and peripheral vasoconstriction (cold hands and feet).
• Subgroup II: This group includes patients who had a viral infection associated with neurologic symptoms, such as Guillain-Barré syndrome, infectious mononucleosis, or atypical viral pneumonia. Even after their infectious disease resolves, these patients continue to require significantly more nocturnal sleep and continue to feel very tired. Although initially these patients are fatigued, subsequently, they have difficulty differentiating fatigue from sleepiness. To fight tiredness, these patients nap and eventually present with complaints of excessive daytime sleepiness. Analysis of cerebral spinal fluid demonstrates moderate lymphocytosis (30-50 cells/mL³ or 30-50 X 10-6/L with mild-to-moderate elevation in protein).
• Subgroup III: These patients do not have a positive family or viral infection history, and the cause of the disorder truly is idiopathic.

Recurrent primary hypersomnia

Kleine-Levin syndrome (KLS) is a rare disorder that starts during adolescence and has a male gender preference.⁸ The patients have recurrent episodes of hypersomnia, which are often associated with compulsive overeating and hypersexuality.⁹ The periods of hypersomnia occur for days to weeks at a time but recur several times a year. In between the symptomatic periods, the patients have normal sleep requirements and do not have excessive daytime sleepiness. Some patients may develop symptoms of irritability, impulsive behavior, depersonalization, hallucinations, depression, and confusion. The etiology of this disorder is not known.^10,11

Mostly men (68%) are affected. The median age of onset is 15 years (range, 4-82 y; 81% during the second decade), and the syndrome may last up to 8 years. The episodes recur every 3-4 months and may last up to 10 days, but they may last longer in women. KLS may be precipitated by infections (38.2%), head trauma (9%), or alcohol consumption (5.4%). Characteristic symptoms include hypersomnia (100%), cognitive changes (96%, including a specific feeling of derealization), eating disturbances (80%), hypersexuality (43%), compulsions (29%), and depressed mood (48%).¹¹

Pathophysiology

A definite mechanism of primary hypersomnia is not known. 

Excessive daytime sleepiness has been described in a subset of patients following viral illnesses such as Guillain-Barré syndrome, hepatitis, mononucleosis, and atypical viral pneumonia. Familial cases associated with HLA-Cw2 and HLA-DR11 genotypes have also been reported.¹³ However, the majority of the patients diagnosed with idiopathic hypersomnia have neither a positive family history or a past medical history of viral illnesses.

In experimental animal studies, destruction of the nonadrenergic neurons of the rostral third of the locus ceruleus complex has produced hypersomnia. While trauma has been associated wit EDS in a case series, cerebrospinal fluid analysis for specific neurotransmitter metabolites did not differentiate posttraumatic EDS patients from narcoleptics or other patients with EDS¹⁴ injury to the adrenergic neurons at the bundle of isthmus has led to hypersomnia associated with a proportional increase of both NREM and REM sleep.¹⁵

Evidence suggests that a dopamine system dysfunction may occur in narcolepsy, while a similar malfunction of the norepinephrine system may occur in idiopathic hypersomnia. Decreased cerebrospinal fluid (CSF) histamine levels have been reported in primary hypersomnia as well as narcolepsy but not in non-central nervous system hypersomnias suggesting that histamine might be an indicator of central versus peripheral origin of hypersomnias.¹⁶

A major advance in the understanding of the pathology of narcolepsy, a closely related disorder, has been made after the discovery of narcolepsy-associated genes in animals, genes involved in the pathology of the hypocretin/orexin ligand and its receptor.¹⁷ Low CSF concentrations of hypocretin-1 and hypocretin-2 in HLA DQB1*0602 were also found in primary hypersomnia and a generalized defect in hcrt-2 transmission may be present in this disorder. As hypocretin peptides excite the histaminergic system by the hypocretin receptor 2¹⁸ , hypocretin deficiency may result in EDS via decreased histaminergic function.¹⁶

Frequency

United States

While the rates of excessive daytime sleepiness complaints in the general population are between 0.5-5% of adults (in surveys without a specific consideration of causes/diagnoses), idiopathic hypersomnia is diagnosed in about 5-10% of individuals who are self referred to a sleep clinic with a chief complaint of daytime sleepiness.³ A precise estimation of idiopathic hypersomnia prevalence is complicated by a lack of clear biological markers or unambiguous diagnostic criteria.

Mortality/Morbidity

The course of primary hypersomnia is chronic, with persistent symptoms of excessive daytime sleepiness occurring without resolution. Daytime sleepiness can lead to depression. Of note, in children, daytime sleepiness can present as hyperactivity.³

Sex

Gender ratio for idiopathic hypersomnia is unknown. Kleine-Levin syndrome affects males approximately 3 times more often than females.³

Age

As with narcolepsy and Klein-Levin syndrome, onset of primary hypersomnia is most common during adolescence and rare in people older than 30 years. The diagnosis of idiopathic hypersomnia is complicated by the fact that differentiating between excessive versus long sleep or normal versus abnormal wakefulness is often difficult in this population.

Clinical

History

DSM-IV-TR diagnostic criteria for 307.44 primary hypersomnia

• The predominant complaint is excessive sleepiness for at least 1 month (or less if recurrent) as evidenced by either prolonged sleep episodes or daytime sleep episodes that occur almost daily.
• The excessive sleepiness causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• The excessive sleepiness is not better accounted for by insomnia and does not occur exclusively during the course of another sleep disorder (eg, narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, parasomnias) and cannot be accounted for by an inadequate amount of sleep.
• The disturbance does not occur exclusively during the course of another mental disorder.
• The disturbance is not due to the direct physiological effects of a substance (eg, drug of abuse, medication) or a general medical condition.

Specify if recurrent

If there are periods of excessive sleepiness that last at least 3 days occurring several times a year for at least 2 years.³

The diagnostic criteria of idiopathic hypersomnia in the revised edition of the ICSD, in addition to the clinical criteria, which are similar to DSM-IV-TR criteria, include one or more of the following polysomnographic features:⁴

• A sleep period that is normal or prolonged in duration
• A sleep latency of less than 10 minutes
• Normal REM sleep latency
• A sleep latency of less than 10 minutes on the Multiple Sleep Latency Test
• Fewer than 2 sleep-onset REM periods

The most typical referral is for the polysymptomatic form of primary hypersomnia and is characterized by the following:^6,19

• Excessive daytime sleepiness leading to prolonged naps that are not refreshing
• Nocturnal sleep of long duration (as much as 12 h or more)
• Sleep drunkenness

These patients do not feel refreshed following naps and, therefore, fight sleepiness as long as they are able. Patients are difficult to awaken from sleep or naps.

Some patients complain of headaches, fainting episodes, orthostatic hypotension, and peripheral vascular complaints of Raynaud phenomenon. Rarely, hypnagogic hallucinations and sleep paralysis may be observed. During long periods of drowsiness, patients might develop automatic behavior, during which they act in a semicontrolled fashion.

In patients with the recurrent form (ie, Kleine-Levine syndrome), hypersomnia occurs for days to weeks several times a year. In between, patients do not have excessive daytime sleepiness. Some patients may develop symptoms of irritability, hypersexuality, hyperphagia, impulsive behavior, depersonalization, hallucinations, depression, and disorientation.

Physical

The patient may appear overtired or even fall asleep in the physician’s office. The rest of the physical examination, however, will not reveal any particular features suggesting a diagnosis of idiopathic hypersomnia.

The physical examination goal is to exclude alternate diagnoses. A diagnosis of obstructive sleep apnea rather than idiopathic hypersomnia should be considered for a patient presenting with hypersomnia associated with central obesity, micrognathia or retrognathia, macroglossia, crowded oropharynx, nasal obstruction, and tonsillar enlargement. An underlying rheumatologic disease, such as active rheumatoid arthritis or osteoarthritis, may cause daytime hyperoxia and sleepiness associated with poor nighttime sleep due to pain. Prior head trauma sequela or a current brain tumor can leave their specific mark on the neurologic examination.

Specific findings may suggest a degenerative neurologic condition (eg, Parkinson or Huntington disease), endocrine dysfunction (eg, hypothyroidism), viral and bacterial infections (eg, hypersomnia secondary to viral encephalitis), pulmonary disease with secondary sleep-related breathing difficulties (eg, chronic bronchitis) or musculoskeletal disorders (eg, rheumatoid arthritis, fibromyalgia).

Recurrent hypersomnia: On the neurologic examination, patients with Klein-Levin syndrome may present with a number of nonspecific findings including nystagmus, dysarthria, and generalized hyperreflexia.

Mental Status Examination

• An overweight patient should be assessed for underlying endocrine problems and sleep apnea.
• If psychomotor retardation or agitation is noted, mental disorders with secondary sleep disturbance need to be ruled out before making a diagnosis of primary hypersomnia.
• Major depressive disorder commonly presents with decreased energy and tiredness and atypical depression presents with hypersomnia. Similarly, speech that is soft in quality, with a decreased rate of production, increased latency of answers might indicate excessive tiredness but also depression.
• Mood might be “down," tired,” or even “depressed,” with mood congruent, decreased range of affect. If this is the case, the meaning of the words needs to be carefully qualified. Is it that the patient has depression (ie, major depressive disorder) or is it that he feels down as a reaction to his oversleeping and decreased ability to function?
• Thought processes should be coherent and goal directed.
• While suicidal ideation is not typical for primary hypersomnia, because of the overlap between sleeping and affective disorders, standard questioning about the presence of suicidal and homicidal ideation is recommended.
• Insight and judgment are most times good.
• Mild cognitive changes in the domains of attention, concentration and short-term memory are occasionally present but most times the cognitive examination should not reveal any significant deficits.

Causes

Also see Pathophysiology.

Primary hypersomnia is an idiopathic disorder. Although head injury or viral infections can cause a disorder resembling primary hypersomnia, the true causes for most cases remain unknown. No genetic, environmental, or other predisposition has been identified.²⁰

Differential Diagnoses

Other Problems to Be Considered

Before making a diagnosis of idiopathic hypersomnia, consider the following:

• Is there a temporal relationship between the onset, exacerbation, and remission of the hypersomnia and its associated features/conditions?
• Is there a family history of hypersomnia versus associated features (a general medical condition, depression, etc)?

• Characteristic symptoms include depressed mood, anhedonia (a loss of interest and pleasure), decreased energy, psychomotor agitation or retardation, decreased or increased appetite (which may result in weight loss or gain), decreased attention and concentration, decreased libido, feelings of guilt or worthlessness, and, in severe cases, suicidal ideation, delusional thought processes, or auditory hallucinations.
• The most common sleep disturbance reported in melancholic depression is poor sleep. Sleep disturbances such as difficulty in sleep initiation and sleep maintenance and/or early awakening are common. Subsequent daytime tiredness resulting in frequent or prolonged naps may be mistaken for excessive daytime sleepiness.
• Hypersomnia, associated with increased appetite, weight gain, mood reactivity (meaning the mood brightens in response to positive events), leaden paralysis (ie, a leaden feeling in the arms or legs), as well as rejection sensitivity are symptoms characteristic of atypical depression.
• If depression is present, a careful history clarifying the chronology of symptoms (did hypersomnia precede or follow the associated depressive symptoms) is required to clarify which is the primary diagnosis.

Narcolepsy: Excessive daytime sleepiness, a history of cataplexy, and the presence of sleep-onset REM periods should allow differentiation of narcolepsy from idiopathic hypersomnia. In the absence of cataplexy, the disorder may be difficult to differentiate. A diagnosis of narcolepsy requires the presence of 2 or more sleep-onset REM periods on the Multiple Sleep Latency Test and association with the human leukocyte antigen (HLA)-DR15 and HLA-DQ6 haplotype. By contrast, patients with primary hypersomnia usually present with longer and less interrupted nocturnal sleep, have more difficulties waking up, and more sleepiness during the daytime (rather than the more discrete "sleep attacks" in narcolepsy). Primary hypersomnia patients also have longer and less refreshing daytime sleep episodes, with little or no dreaming during daytime naps (as opposed to the sleep-onset REM periods seen in narcolepsy).³

Circadian rhythm sleep disorders: Delayed sleep phase syndrome is a diagnostic consideration in some patients whose main complaints are extreme difficulty awakening at a desired time and excessive morning sleepiness. An abnormal sleep-wake schedule (with shifted or irregular hours) is often present in individuals with circadian rhythm sleep disorder.³ These patients do not have excessive daytime sleepiness in the later half of the day and are not able to fall asleep until late at night.

Other psychiatric disorders: Hypersomnia associated with dysthymia and related mood disorders is observed frequently. The presentation is usually later in life. A low-grade chronic depression and inability to cope with stressful situations are observed. The sleep disturbance in psychiatric patients with the chief complaint of hypersomnia appears to be associated with a centrally driven hyperarousal, whereas primary hypersomnia is associated with a centrally driven hypoarousal. Multiple Sleep Latency Test findings do not demonstrate short sleep latency. Persistent or relapsing fatigue that does not resolve with bedrest characterizes chronic fatigue syndrome. Polysomnographic recording shows reduced sleep efficiency and alpha intrusion into sleep on electroencephalogram (EEG).

Workup

Laboratory Studies

• Primary hypersomnia is a diagnosis of exclusion. Other causes of excessive daytime somnolence should be ruled out before a diagnosis of primary hypersomnia is made.
• Patients should receive a complete blood cell count, screening biochemistry tests, and thyroid-stimulating hormone tests to exclude common physical disorders that may present with complaints of excessive tiredness, often expressed as excessive sleepiness by patients.
• A drug screen is indicated if substance-induced sleep disorder needs to be ruled out.

Other Tests

As excessive sleepiness is essentially a self-reported subjective complaint, a number of tests have been created with the goal of increasing the data collection validity and reliability. Commonly used scales for a quantitative, systematic assessment of excessive sleepiness are the Epworth Sleepiness Scale (ESS) and Stanford Sleepiness Scale (SSS). While helpful, these scales remain essentially subjective in nature, which raises questions about the characteristics of sleepiness as assessed by subjective (eg, ESS, SSS) versus objective methods (eg, PSG, MST).^23,24

Procedures

Polysomnography (PSG) and Multiple Sleep Latency Test (MSLT)²⁵

• Complete in-laboratory PSG studies are essential to exclude other sleep disorders, particularly sleep breathing disorder, periodic limb movement disorder, and narcolepsy. Nocturnal PSG findings in primary hypersomnia include a short sleep latency, absence of arousals or awakenings, normal distribution of REM and NREM sleep, and normal to prolonged sleep duration.
• A PSG study completion is required prior to the MSLT to objectively characterize preceding sleep and uncover potential causes of sleep fragmentation. The PSG must have confirmed at least 6 hours of sleep for the MSLT results to be considered in diagnosing primary hypersomnia.
• Sleep latency on MSLT is usually short (8–10 minutes or less), and in contrast to narcolepsy, sleep-onset REM periods (the occurrence of REM sleep within 20 minutes of sleep onset) are not typically seen.
• Breathing-related sleep disturbances and frequent limb movements disrupting sleep are not present.
• The following PSG features are required for the diagnosis of primary hypersomnia:
  • A sleep period that is normal or prolonged in duration
  • A sleep latency of less than 10 minutes
  • Normal REM sleep latency
  • A sleep latency of less than 10 minutes on the Multiple Sleep Latency Test
  • Fewer than 2 sleep-onset REM periods.
• The MSLT is performed to evaluate the presence of pathological sleepiness. The subject is studied during 5 daytime naps taken 2 hours apart. According to 2 studies, the mean MSLT score in primary hypersomnia is slightly higher than the score in narcolepsy. Mean MSLT score was found to be 6.5 ± 3.2 minutes for idiopathic hypersomnolence versus 3.3 ± 3.3 minutes for narcolepsy. Narcolepsy is excluded by the absence of sleep-onset REM periods on the 5-nap MSLT.

In recurrent primary hypersomnia (ie, Kleine-Levin syndrome), routine EEG studies performed during hypersomnia, show a general slowing of the background rhythm and paroxysmal bursts of theta activity. Nocturnal polysomnography shows prolonged sleep duration and decreased sleep latency (<10 min). In addition, sleep-onset REM has been reported during symptomatic periods.³

Primary hypersomnia. Polysomnographic study demonstrates apnea (absence of carbon dioxide fluctuation indicating no flow), chest wall paradox, abrupt increase in tidal volume at the end of apnea, and oxygen desaturation. All of these features are consistent with obstructive sleep apnea.

Primary hypersomnia. In contrast to obstructive sleep apnea, mixed apnea shows absence of respiratory efforts in the first segment of the apnea.

Primary hypersomnia. Periodic limb movements show intermittent leg electromyogram activity accompanied by electroencephalogram arousals.

Treatment

Medical Care

Because the underlying cause of idiopathic hypersomnia is unknown, treatment remains symptomatic in nature. Severe idiopathic hypersomnia is a disabling problem that often leads to permanent unemployment and responds poorly to medical treatment.^9,7 The American Academy of Sleep Medicine practice parameters state that successful treatment of hypersomnia of central origin requires an accurate diagnosis, individual tailoring of therapy to produce maximum possible return of function, and regular follow-up to monitor response to therapy. Modafinil, sodium oxybate, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, and selegiline are effective treatments for excessive sleepiness associated with narcolepsy and primary hypersomnias. Scheduled naps can be beneficial to combat sleepiness in these patients.²⁶

• Behavioral approaches and sleep hygiene techniques are recommended, although they have little overall positive impact on this disease.
• Medications that have been used in the treatment of this disorder include tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), clonidine, levodopa, bromocriptine, amantadine, methysergide, pemoline (as of October 2005, this is no longer available in the United States; risk of liver toxicity outweighs benefits), and modafinil.
  • Therapy for idiopathic hypersomnolence involves maintaining the patient on a daily use of stimulants. The drug dose is titrated so that the patient stays alert during the day, but adverse effects should be avoided.
  • Methylphenidate, mazindol (withdrawn from the US market in 2001), and dextroamphetamine are the most commonly prescribed medications.
• Modafinil has proved clinically useful in the treatment of narcolepsy and other causes of excessive daytime sleepiness such as idiopathic hypersomnolence.²⁷ It is a psychostimulant that enhances wakefulness and vigilance, but its pharmacological profile is notably different from the amphetamines, methylphenidate (Ritalin), or cocaine. Modafinil is less likely to produce side effects such as jitteriness, anxiety, or excess locomotor activity or lead to a hypersomnolent rebound effect. It is long-acting, the normal elimination half-life of modafinil in humans is between 12-15 hours.^1,28
• The mechanism of action of modafinil isn't fully understood. Modafinil induces wakefulness in part by its action in the anterior hypothalmus. Its dopamine-releasing action in the nucleus accumbens is weak and dose-dependent; the likelihood of a euphoric response, and therefore the abuse potential and tolerance, is small. Modafinil has central alpha 1-adrenergic agonist effects (ie, it directly stimulates the receptors). Modafinil inhibits the reuptake of noradrenaline by the noradrenergic terminals on sleep-promoting neurons of ventrolateral preoptic nucleus (VLPO). More significant, perhaps, is its ability to increase excitatory glutaminergic transmission and reduce local GABAergic transmission, thereby diminishing GABA(A) receptor signaling on the mesolimbic dopamine terminals.^29,28

Consultations

The diagnosis of primary hypersomnia is made after excluding neurologic, pulmonary, and psychiatric disorders known to cause excessive sleepiness. Therefore, if an underlying cause is suggested, appropriate consultations with a neurologist, pulmonologist, and psychiatrist should be obtained.

Activity

Caution is recommended in activities where hypersomnolence may be hazardous.

Medication

Patients often require drug therapy to treat daytime hypersomnolence. Prior to initiating therapy with stimulants, clearly establish a diagnosis and consider potential for abuse.^7,22

Modafinil, a wake-promoting agent, is approved for treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome (OSAHS), and shift-work sleep disorder (SWSD).^29,28 The studies have shown significant benefits on various objective measures and subjective estimates of excessive sleepiness. The clinical efficacy of modafinil, combined with improved safety over CNS stimulants, has made it the most prescribed medication for the treatment of excessive sleepiness associated with narcolepsy. Unlike many other medications used for excessive sleepiness, modafinil is not known to be abused. The most common adverse event reported in clinical studies was headaches; most were transient and mild-to-moderate in severity. Modafinil also has the potential for interactions with other drugs metabolized via cytochrome P450 enzyme pathways.

For Kleine-Levin syndrome, somnolence can decrease with stimulants (mainly amphetamines), while neuroleptics and antidepressants are of poor benefit. Lithium, rather than carbamazepine or other antiepileptics, had a higher success rate for stopping relapses.³⁰ For secondary Kleine-Levin syndrome, patients tend to be older and have more frequent and longer episodes but present with clinical symptoms and treatment responses similar to those of primary cases.¹¹

Central Nervous System Stimulant

These agents have wake-promoting activities.

Modafinil (Provigil)

May exert stimulant effects by decreasing GABA-mediated neurotransmission. Has wake-promoting actions similar to sympathomimetic agents. Improves wakefulness in patients with excessive daytime hypersomnolence. Has been used in narcolepsy and primary hypersomnia. Mechanism of action is unclear.

Dosing

Adult

200 mg/d PO qam; may increase to 400 mg/d

Pediatric

<16 years: Not established
>16 years: Administer as in adults

Interactions

May decrease levels of cyclosporine or steroidal contraceptives, and to a lesser degree, theophylline; modafinil may increase drug concentration levels of diazepam, propranolol, and phenytoin

Contraindications

Documented hypersensitivity

Precautions

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

Monitor patients closely for signs of misuse or abuse, especially those with a history of drug or stimulant abuse such as methylphenidate, amphetamine, and cocaine; leukopenia has been reported in pediatric patients; may cause serious life-threatening rash (ie, Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms), hypersensitivity reactions (eg, angioedema, multiorgan reactions), and psychiatric symptoms (eg, anxiety, mania, hallucinations, suicidal ideation)

Methylphenidate (Ritalin)

Used for symptomatic management of primary hypersomnolence whenever patient needs to be alert or engages in activities where hypersomnolence may be hazardous. Blocks the reuptake mechanism of dopaminergic neurons. Stimulates cerebral cortex and subcortical structures.

Dosing

Adult

10 mg PO bid/tid, not to exceed 60 mg/d

Pediatric

50 mg PO qd

Interactions

Reduces effects of guanethidine and bretylium; toxicity of phenytoin, tricyclic antidepressants, warfarin, primidone, and phenobarbital may increase when administered concurrently with methylphenidate; MAOIs increase toxicity of methylphenidate

Contraindications

Documented hypersensitivity; glaucoma, Tourette syndrome, motor tics, patients with agitation, tension, and anxiety

Precautions

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

Caution in dementia, seizures, hypertension, structural cardiac abnormalities, or other cardiovascular disease; increased risk for sudden death associated with use in patients with serious heart conditions; sudden death, stroke, and MI have also been reported in adults receiving stimulant drugs at usual doses; may exacerbate preexisiting psychiatric disorders and increase the potential for emergence of treatment-related psychotic or manic symptoms; may increase risk of temporary growth suppression

Dextroamphetamine (DextroStat, Dexedrine Spansules)

Increases amount of circulating dopamine and norepinephrine in cerebral cortex by blocking reuptake of norepinephrine or dopamine from synapse.

Dosing

Adult

5-30 mg/d PO in divided doses 30-60 min before meals

Pediatric

<3 years: Not established
3-5 years: 2.5 mg PO qam initially; increase by 2.5 mg/d qwk to response
>5 years: 5 mg PO qd or bid; increase by 5 mg/d qwk to response; not to exceed 40 mg/d

Interactions

Coadministration with MAOIs may precipitate hypertensive crisis and with anesthetics, may precipitate arrhythmias; dextroamphetamine may increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs, phenytoin, and norepinephrine

Contraindications

Documented hypersensitivity; hypertension, MAOIs, advanced arteriosclerosis, hyperthyroidism, glaucoma

Precautions

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

Caution in angina, glaucoma, cardiovascular disease, and psychopathic personalities

Dextroamphetamine and amphetamine mixtures (Adderall)

Produce CNS and respiratory stimulation. CNS effect may occur in cerebral cortex and reticular activating system. May have direct effect on both alpha- and beta-receptor sites in peripheral system as well as release stores of norepinephrine in adrenergic nerve terminals.
Mixture contains various salts of amphetamine and dextroamphetamine.

Available as 5-, 7.5-, 10-, 12.5-, 15-, 20-, and 30-mg scored tablets.

Dosing

Adult

5-60 mg/d PO divided bid/tid

Pediatric

<3 years: Not established
3-6 years: 2.5 mg/d PO qd initially; increase by 2.5 mg qwk
>6 years: 5 mg PO qd or divided bid initially; increase by 5 mg qwk; not to exceed 40 mg/d

Interactions

Coadministration with MAOIs may precipitate hypertensive crisis; anesthetics may precipitate arrhythmias; dextroamphetamine may increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs, phenytoin, and norepinephrine

Contraindications

Documented hypersensitivity; hypertension, advanced arteriosclerosis, hyperthyroidism, glaucoma, agitated states, within 14 d of MAOIs administration

Precautions

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

Caution in nephritis, hypertension, angina, glaucoma, cardiovascular disease, psychopathic personalities, or history of drug abuse

Follow-up

Prognosis

• After a typical onset between the ages 15-30 years, untreated primary hypersomnia presents a chronic but stable course.
• Idiopathic hypersomnia is a lifelong disorder with no tendency to remit spontaneously.
• Consequences of this disease are mostly social and professional in nature.

Patient Education

• While treating patients with primary hypersomnia, the patient's close family should be involved in the overall education and decision-making process.
• Because these disorders may lead to marriage breakdown, extensive counseling for the patient's partners, educating them about the symptomatology and treatment options, must be part of a comprehensive management plan.
• Patients with primary hypersomnia often need significant support because they are at risk of being misunderstood as being incompetent or slothful. Therefore, education of relatives, friends, and colleagues helps the patient function much better with this incurable disease.
• For excellent patient education resources, visit eMedicine's Sleep Disorders Center. Also, see eMedicine's patient education articles Disorders That Disrupt Sleep (Parasomnias) and Narcolepsy.
• Medline Plus/NIH provides concise and to the point summaries of the diagnosis and recommendations for patients and families dealing with primary hypersomnia and Kleine-Levine syndrome.
• The Mayo clinic offers an additional, more comprehensive patient resource on idiopathic/primary hypersomnia.

Miscellaneous

Medicolegal Pitfalls

• Distinguish primary hypersomnia from sleep-related breathing disorders, particularly upper airway resistance syndrome.
• During automatic behavior episodes, these patients may endanger themselves through risk of injury.
• Patients develop tolerance to their medications; exercise caution in prescribing medications.
• Physicians have a legal responsibility to know which medical conditions may impede driving ability, to diagnose these conditions in their patients, and to discuss implications of these conditions.
  • The requirement to report unfit drivers varies among different jurisdictions and interpretations of the law vary among the courts.
  • Therefore, physician’s risks of liability are unclear. Physicians may face legal action by their patients if they fail to counsel the patients on the dangers of driving associated with certain medications or medical conditions.
  • Physician’s legal responsibilities to report patients with certain medical conditions, when required by law, override their ethical responsibilities to keep patient’s medical information confidential.

Special Concerns

• The ICSD describes primary hypersomnia as idiopathic hypersomnia. Recurrent hypersomnia is classified separately to describe the recurrent form of primary hypersomnia according to the DSM-IV-TR.
• Kleine-Levine syndrome (See Background.)

Multimedia

Media file 1: Primary hypersomnia. Polysomnographic study demonstrates apnea (absence of carbon dioxide fluctuation indicating no flow), chest wall paradox, abrupt increase in tidal volume at the end of apnea, and oxygen desaturation. All of these features are consistent with obstructive sleep apnea.

Media file 2: Primary hypersomnia. In contrast to obstructive sleep apnea, mixed apnea shows absence of respiratory efforts in the first segment of the apnea.

Media file 3: Primary hypersomnia. Periodic limb movements show intermittent leg electromyogram activity accompanied by electroencephalogram arousals.

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Keywords

idiopathic hypersomnia, primary hypersomnia, sleep disorder treatment, narcolepsy, sleep drunkenness, excessive daytime sleepiness, obstructive sleep apnea, sleep apnea, Kleine-Levin syndrome

Contributor Information and Disclosures

Author

Adrian Preda, MD, Health Sciences Associate Professor of Psychiatry and Human Behavior, University of California Irvine School of Medicine
Adrian Preda, MD is a member of the following medical societies: International Congress of Schizophrenia Research, Schizophrenia International Research Society, and Society of Biological Psychiatry
Disclosure: Nothing to disclose.

Medical Editor

Jennifer S Morse, MD, Assistant Clinical Professor, Department of Psychiatry, University of California at San Diego
Jennifer S Morse, MD is a member of the following medical societies: Academy of Psychosomatic Medicine, Aerospace Medical Association, and American Psychiatric Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Iqbal Ahmed, MBBS, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii
Iqbal Ahmed, MBBS is a member of the following medical societies: Academy of Psychosomatic Medicine, American Association for Geriatric Psychiatry, American Neuropsychiatric Association, and American Psychiatric Association
Disclosure: Nothing to disclose.

CME Editor

Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin
Harold H Harsch, MD is a member of the following medical societies: American Psychiatric Association
Disclosure: lilly Honoraria Speaking and teaching; Forest Labs Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; Pfizer Grant/research funds Speaking and teaching; Northstar Grant/research funds Research; Novartis Grant/research funds research; Pfizer  Speaking and teaching; Sanofi-avetis Grant/research funds research; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research

Chief Editor

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Stephen Soreff, MD is a member of the following medical societies: American College of Mental Health Administration and American Psychosomatic Society
Disclosure: Nothing to disclose.

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