The non-stimulant wake-promoting medications approved for use in narcolepsy include modafinil and armodafinil. Their pharmacology is not completely understood, but these medications "appear to influence brain chemistry that increases wakefulness." They elevate hypothalamic histamine levels, and they are known to bind to the dopamine transporter, thereby inhibiting dopamine reuptake. Modafinil can cause uncomfortable side effects, including nausea, headache, and a dry mouth for some patients, while other patients report no noticeable improvement even on relatively high dosages. They may also "interact with low-dose contraceptives, potentially reducing efficacy, although the scientific data supporting this claim is weak and rests on poorly documented anecdotes." New histamine-directed wake-promoting medications are currently under development (see Histamine-directed medications).

Atomoxetine (or reboxetine in Europe) is an adrenergic reuptake inhibitor which increases wakefulness (generally less strongly than the medications which act on dopamine) and which has been argued to have a "clear use in the therapeutic arsenal against narcolepsy and hypersomnia although undocumented by clinical trials."

Ritanserin is a serotonin antagonist that has "been shown to improve daytime alertness and subjective sleep quality in patients on their usual narcolepsy medications." It is intended as an adjunct (supplement to another main therapeutic agent), and although it is not available in the US, it is available in Europe.

Although anti-depressants, in general, have not been found to be helpful for treatment of idiopathic hypersomnia, bupropion specifically is known to have wake-promoting effects. "It is a low potency nonspecific monoamine reuptake inhibitor that also has DAT [dopamine-reuptake] inhibitory effects."

There are several stimulants approved by the FDA for treatment of excessive sleepiness due to narcolepsy. These include methylphenidate (e.g., Ritalin) and dextroamphetamine, among others. Selegiline may also be useful, as it is "primarily a metabolic precursor of amphetamine and exerts most of its therapeutic effects through amphetamine metabolism." Increased dopamine release is felt to be the main property explaining wake-promotion from these medications. Although stimulants can effectively reduce sleepiness in the short to medium term, they are rarely effective long-term, as patients frequently become resistant to their effects. In addition, there are unpleasant potential side effects, which include heart problems, aggressive behavior, and dependence. Insomnia is another common side effect and may require additional treatment.

Mazindol is a stimulant similar to amphetamines that "has been shown to be effective in treating hypersomnia in narcoleptics." However, it is not currently approved in the US.

Caffeine is one of the safer nondopaminergic wake-promoting compounds. It is widely used but "has intolerable side effects at high doses (including cardiovascular), and it is generally not efficient enough for patients with hypersomnia or narcolepsy."

Research suggests that hypnosis may be helpful in alleviating some types and manifestations of sleep disorders in some patients. "Acute and chronic insomnia often respond to relaxation and hypnotherapy approaches, along with sleep hygiene instructions." Hypnotherapy has also helped with nightmares and sleep terrors. There are several reports of successful use of hypnotherapy for parasomnias specifically for head and body rocking, bedwetting and sleepwalking.

Hypnotherapy has been studied in the treatment of sleep disorders in both adults and children.

Melatonin taken an hour or so before the usual bedtime may induce sleepiness. Taken this late, it does not, of itself, affect circadian rhythms, but a decrease in exposure to light in the evening is helpful in establishing an earlier pattern. In accordance with its phase response curve (PRC), a very small dose of melatonin can also, or instead, be taken some hours earlier as an aid to resetting the body clock; it must then be small enough not to induce excessive sleepiness.

Side effects of melatonin may include sleep disturbance, nightmares, daytime sleepiness, and depression, though the current tendency to use lower doses has decreased such complaints. Large doses of melatonin can even be counterproductive: Lewy et al. provide support to "the idea that too much melatonin may spill over onto the wrong zone of the melatonin phase-response curve." The long-term effects of melatonin administration have not been examined. In some countries, the hormone is available only by prescription or not at all. In the United States and Canada, melatonin is on the shelf of most pharmacies and herbal stores. The prescription drug Rozerem (ramelteon) is a melatonin analogue that selectively binds to the melatonin MT and MT receptors and, hence, has the possibility of being effective in the treatment of DSPD.

A review by the US Department of Health and Human Services found little difference between melatonin and placebo for most primary and secondary sleep disorders. The one exception, where melatonin is effective, is the "circadian abnormality" DSPD. Another systematic review found inconsistent evidence for the efficacy of melatonin in treating DSPD in adults, and noted that it was difficult to draw conclusions about its efficacy because many recent studies on the subject were uncontrolled.

Modafinil (Provigil) is a stimulant approved in the US for treatment of shift-work sleep disorder, which shares some characteristics with DSPD. A number of clinicians prescribe it for DSPD patients, as it may improve a sleep-deprived patient's ability to function adequately during socially desirable hours. It is generally not recommended to take modafinil after noon; modafinil is a relatively long-acting drug with a half-life of 15 hours, and taking it during the later part of the day can make it harder to fall asleep at bedtime.

Vitamin B was, in the 1990s, suggested as a remedy for DSPD, and is still recommended by some sources. Several case reports were published. However, a review for the American Academy of Sleep Medicine in 2007 concluded that no benefit was seen from this treatment.

In a test tube model, clarithromycin (an antibiotic approved by the FDA for the treatment of infections) was found to return the function of the GABA system to normal in patients with primary hypersomnias. Investigators therefore treated a few patients with off-label clarithromycin, and most felt their symptoms improved with this treatment. In order to help further determine whether clarithromycin is truly beneficial for the treatment of narcolepsy and idiopathic hypersomnia, a small, double-blind, randomized, controlled clinical trial was completed in 2012. "In this pilot study, clarithromycin improved subjective sleepiness in GABA-related hypersomnia. Larger trials of longer duration are warranted." In 2013, a retrospective review evaluating longer-term clarithromycin use showed efficacy in a large percentage of patients with GABA-related hypersomnia. “It is important to note that the positive effect of clarithromycin is secondary to a benzodiazepine antagonist-like effect, not its antibiotic effects, and treatment must be maintained.”

A review of the evidence in 2012 concluded that current research is not rigorous enough to make recommendations around the use of acupuncture for insomnia. The pooled results of two trials on acupuncture showed a moderate likelihood that there may be some improvement to sleep quality for individuals with a diagnosis insomnia. This form of treatment for sleep disorders is generally studied in adults, rather than children. Further research would be needed to study the effects of acupuncture on sleep disorders in children.

Caffeine is the most widely used alerting drug in the world and has been shown to improve alertness in simulated night work. Caffeine and naps before a night shift reduces sleepiness during the shift. Modafinil and armodafinil are non-amphetamine alerting drugs originally developed for the treatment of narcolepsy that have been approved by the FDA (the US Food and Drug Administration) for excessive sleepiness associated with SWSD.

People with narcolepsy can be substantially helped, but not cured. Treatment is tailored to the individual, based on symptoms and therapeutic response. The time required to achieve optimal control of symptoms is highly variable and may take several months or longer. Medication adjustments are frequently necessary, and complete control of symptoms is seldom possible. While oral medications are the mainstay of formal narcolepsy treatment, lifestyle changes are also important.

The main treatment of excessive daytime sleepiness in narcolepsy is central nervous system stimulants such as methylphenidate, amphetamine, dextroamphetamine, modafinil, and armodafinil. In late 2007 an alert for severe adverse skin reactions to modafinil was issued by the FDA.

Another drug that is used is atomoxetine, a non-stimulant and a norepinephrine reuptake inhibitor (NRI), which has no addiction liability or recreational effects. In many cases, planned regular short naps can reduce the need for pharmacological treatment of the EDS, but only improve symptoms for a short duration. A 120-minute nap provided benefit for 3 hours in patient alertness whereas a 15-minute nap provided no benefit. Daytime naps are not a replacement for nighttime sleep. Ongoing communication between the health care provider, patient, and the patient's family members is important for optimal management of narcolepsy.

Another FDA-approved treatment option for narcolepsy is sodium oxybate, also known as sodium gamma-hydroxybutyrate (GHB). It can be used for cataplexy associated with narcolepsy and excessive daytime sleepiness associated with narcolepsy.

Narcolepsy has sometimes been treated with selective serotonin reuptake inhibitors and tricyclic antidepressants, such as clomipramine, imipramine, or protriptyline, as well as other drugs that suppress REM sleep. Venlafaxine, an antidepressant which blocks the reuptake of serotonin and norepinephrine, has shown usefulness in managing symptoms of cataplexy, however, it has notable side-effects including sleep disruption.

A strict schedule and good sleep hygiene are essential in maintaining any good effects of treatment. With treatment, some people with mild DSPD may sleep and function well with an earlier sleep schedule. Caffeine and other stimulant drugs to keep a person awake during the day may not be necessary, and should be avoided in the afternoon and evening, in accordance with good sleep hygiene. A chief difficulty of treating DSPD is in "maintaining" an earlier schedule after it has been established. Inevitable events of normal life, such as staying up late for a celebration or deadline, or having to stay in bed with an illness, tend to reset the sleeping schedule to its intrinsic late times.

Long-term success rates of treatment have seldom been evaluated. However, experienced clinicians acknowledge that DSPD is extremely difficult to treat. One study of 61 DSPD patients, with average sleep onset at about 3 a.m. and average waking time of about 11:30 a.m., was followed with questionnaires to the subjects after a year. Good effect was seen "during" the six-week treatment with a large daily dose of melatonin. Follow-up showed that over 90% had relapsed to pre-treatment sleeping patterns within the year, 29% reporting that the relapse occurred within one week. The mild cases retained changes significantly longer than the severe cases.

Treatment of EDS relies on identifying and treating the underlying disorder which may cure the person from the EDS. Drugs like modafinil, Armodafinil, Xyrem (sodium oxybate) oral solution, have been approved as treatment for EDS symptoms in the U.S. There is declining usage of other drugs such as methylphenidate (Ritalin), dextroamphetamine (Dexedrine), amphetamine (Adderall), lisdexamfetamine (Vyvanse), methamphetamine (Desoxyn), and pemoline (Cylert), as these psychostimulants may have several adverse effects and may lead to dependency when illicitly misused.

RBD is treatable. Medications are prescribed for RBD based on symptoms. Low doses of clonazepam is most effective with a 90% success rate. How this drug works to restore REM atonia is unclear: It is thought to suppress muscle activity, rather than directly restoring atonia. Melatonin is also effective and can also be prescribed as a more natural alternative. For those with Parkinson's and RBD, Levodopa is a popular choice. Pramipexole is another drug which can be an effective treatment option. Recent evidence has shown melatonin and clonazepam to be comparably effective in treatment of RBD with patients who received melatonin treatment reporting fewer side effects. In addition, patients with neurodegenerative diseases such as Parkinson's disease reported more favorable outcomes with melatonin treatment.

In addition to medication, it is wise to secure the sleeper's environment in preparation for episodes by removing potentially dangerous objects from the bedroom and either place a cushion round the bed or moving the mattress to the floor for added protection against injuries. Some extreme sufferers sleep in a sleeping bag zipped up to their neck, and wear mittens so they can't unzip it until they awake in the morning.

Patients are advised to maintain a normal sleep schedule, avoid sleep deprivation, and keep track of any sleepiness they may have. Treatment includes regulating neurologic symptoms and treating any other sleep disorders that might interfere with sleep. Sleep deprivation, alcohol, certain medications, and other sleep disorders can all increase RBD and should be avoided if possible.

Behavioral treatment can be effective in some cases. Sedative hypnotics may also help relieve the symptoms. Additionally, education about normal patterns of the sleep-wake cycle may alleviate anxiety in some patients. For patients with severe depression resulting from the fear of having insomnia, electroconvulsive therapy appears to be a safe and effective treatment.

Melatonin is a hormone secreted by the pineal gland in darkness, normally at night. Its production is suppressed by light exposure, principally blue light around 460 to 480 nm. Light restriction, or dark therapy, in the hours before bedtime allows its production. Dark therapy does not require total darkness. Amber or orange colored goggles eliminate blue light to the eyes while allowing vision.

Melatonin is also available as an oral supplement. In the US and Canada, the hormone melatonin is not classified as a drug; it is sold as a dietary supplement. In other countries it requires a prescription or is unavailable. Although it is not licensed by the FDA as a treatment for any disorder, there have been no serious side effects or complications reported to date.

Melatonin has been shown to accelerate the adaptation of the circadian system to a nighttime work schedule. Melatonin may benefit daytime sleep in night workers by an additional direct sleep promoting mechanism. Melatonin treatment may increase sleep length during both daytime and nighttime sleep in night shift workers.

Because insomnia is a common symptom of depression, antidepressants are effective for treating sleep problems whether or not they are associated with depression. While all antidepressants help regulate sleep, some antidepressants such as amitriptyline, doxepin, mirtazapine, and trazodone can have an immediate sedative effect, and are prescribed to treat insomnia. Amitriptyline and doxepin both have antihistaminergic, anticholinergic, and antiadrenergic properties, which contribute to both their therapeutic effects and side effect profiles, while mirtazapine's side effects are primarily antihistaminergic, and trazodone's side-effects are primarily antiadrenergic. Mirtazapine is known to decrease sleep latency (i.e., the time it takes to fall asleep), promoting sleep efficiency and increasing the total amount of sleeping time in people with both depression and insomnia.

Agomelatine, a melatonergic antidepressant with sleep-improving qualities that does not cause daytime drowsiness, is licensed for marketing in the European Union and TGA Australia. After trials in the United States its development for use there was discontinued in October 2011 by Novartis, who had bought the rights to market it there from the European pharmaceutical company Servier.

As an alternative to taking prescription drugs, some evidence shows that an average person seeking short-term help may find relief by taking over-the-counter antihistamines such as diphenhydramine or doxylamine. Diphenhydramine and doxylamine are widely used in nonprescription sleep aids. They are the most effective over-the-counter sedatives currently available, at least in much of Europe, and in Canada, Australia, and the United States, and are more sedating than some prescription hypnotics. Antihistamine effectiveness for sleep may decrease over time, and anticholinergic side-effects (such as dry mouth) may also be a drawback with these particular drugs. While addiction does not seem to be an issue with this class of drugs, they can induce dependence and rebound effects upon abrupt cessation of use. However, people whose insomnia is caused by restless legs syndrome may have worsened symptoms with antihistamines.

Middle-of-the-night insomnia is often treated with medication, although currently Intermezzo (zolpidem tartrate sublingual tablets) is the only Food and Drug Administration-approved medication specifically for treating MOTN awakening. Because most medications usually require 6–8 hours of sleep to avoid lingering effects the next day, these are often used every night at bedtime to prevent awakenings. Medication may not be prescribed in some cases, especially if the cause turns out to be the patient ingesting too much fluid during the day or just before they go to sleep.

Sleep restriction therapy and stimulus control therapy as described in insomnia have shown significance in treating middle of night insomnia.

Some studies have shown that zaleplon, which has a short elimination half-life, may be suitable for middle-of-the-night administration because it does not impair next day performance.

Treatment for sexsomnia involves one or more of the following:

- prescription medications

- CPAP

- lifestyle changes

Though no large trials have taken place which focus on the treatment of sleep paralysis, several drugs have promise in case studies. Two trials of GHB for people with narcolepsy demonstrated reductions in sleep paralysis episodes.

Medical treatment starts with education about sleep stages and the inability to move muscles during REM sleep. People should be evaluated for narcolepsy if symptoms persist. The safest treatment for sleep paralysis is for people to adopt healthier sleeping habits. However, in more serious cases tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs) may be used. Despite the fact that these treatments are prescribed there is currently no drug that has been found to completely interrupt episodes of sleep paralysis a majority of the time.

The condition may worsen as a result of persistent attempts to treat the symptoms through conventional methods of dealing with insomnia. The prescription of hypnotics or stimulants may lead to drug dependency as a complication.

Nonetheless, chronic SSM may increase risk for depression, anxiety, and substance abuse. It has also been noted that patients with this condition may sometimes opt to take medications over other treatments "for the wrong reasons (e.g. because of euphoriant properties)."

Clonazepam, commonly referred to as Klonopin, has been prescribed as treatment for sexsomnia. This medication is classified as a benzodiazepine and works by acting on the GABA-A receptors present in the central nervous system (CNS). Benzodiazepines open the chloride channels to allow chloride to enter the neuron. The most common use of this medication is for the treatment of anxiety, seizures, panic disorders, and sleep disorders. Anticonvulsant therapy is used to treat sexual behaviors that result secondary to sleep related epilepsy.

In the 1980s and 1990s, several trials of melatonin administration to totally blind individuals without light perception produced improvement in sleep patterns, but it was unclear at that time if the benefits were due to entrainment from light cues. Then, using endogenous melatonin as a marker for circadian rhythms, several research groups showed that appropriately timed melatonin administration could entrain free-running rhythms in the totally blind. For example, Sack et al. found that 6 out of 7 patients treated with 10 mg melatonin at bedtime were normally entrained. When the dose was gradually reduced to 0.5 mg in three of the subjects, entrainment persisted. Subsequently, it was shown that treatment initiated with the 0.5 mg dose produced entrainment. One subject who failed to entrain at a higher dose was successfully entrained at a lower dose. A low dose produces melatonin blood levels that are similar to the concentrations naturally produced by nightly pineal secretion.

Products containing melatonin are available as dietary supplements in the United States and Canada, available over the counter. These "supplements" do not require FDA approval. As prescription drugs may be prescribed off-label, treatment recommendations for non-24 in the blind may vary.

There has been a constant growth in the field of melatonin and melatonin receptor agonists since the 1980s. In 2005 Ramelteon (Rozerem) was the first melatonin agonist to be approved in the United States (US), indicated for insomnia treatment in adults. Melatonin in the form of prolonged release (trade name Circadin) was approved in 2007 in Europe (EU) for use as a short-term treatment, in patients 55 years and older, for primary insomnia. Tasimelteon (trade name Hetlioz) received FDA-approval in January 2014 for persons diagnosed with non-24. TIK-301 (Tikvah Therapeutics, Atlanta, USA) has been in phase II clinical trial in the United States since 2002 and the FDA granted it orphan drug designation in May 2004, for use as a treatment for circadian rhythm sleep disorder in blind individuals without light perception as well as individuals with tardive dyskinesia.

Enforcing a 24-hour sleep–wake schedule using alarm clocks or family interventions is often tried but usually unsuccessful. Bright light exposure on awakening to counteract the tendency for circadian rhythms to delay, similar to the treatment for delayed sleep phase disorder, and seasonal affective disorder (SAD) has been found to be effective in some cases, as has melatonin administration in the subjective late afternoon or evening. Light therapy involves at least 20 minutes of exposure to 3000 to 10000 lux light intensity. Going outside on a bright sunny day can accomplish the same benefit as special light fixtures (light boxes). Bright light therapy combined with the use of melatonin as a chronobiotic and avoidance of light before bedtime may be the most effective treatment. Melatonin administration shifts circadian rhythms according to a phase response curve (PRC) that is essentially the inverse of the light PRC. When taken in the late afternoon or evening, it resets the clock earlier; when taken in the morning, it shifts the clock later. Therefore, successful entrainment depends on the appropriate timing of melatonin administration. The accuracy needed for successfully timing the administration of melatonin requires a period of trial and error, as does the dosage. In addition to natural fluctuations within the circadian rhythm, seasonal changes including temperature, hours of daylight, light intensity and diet are likely to affect the efficacy of melatonin and light therapies since these exogenous zeitgebers would compete for hormonal homoeostasis. Further to this there are unforeseen disruptions to contend with even when a stabilised cycle is achieved; such as travel, exercise, stress, alcohol or even the use of light emitting technology close to a subjective evening/night.

Hypnotics and/or stimulants (to promote sleep and wakefulness, respectively) have sometimes been used. Typically a sleep diary is requested to aid in evaluation of treatment, though the emergence of modern actigraphy devices can also assist in the logging of sleep data. Additionally, graphs can now be generated using mobile phone applications, utilising internal accelerometers which are present in most smartphones in use today. The graphs and basic sleep diary records can be shared with a physician. However, due to the lack of clinical accuracy they should not be used for diagnosis, but instead to monitor the cycle and general progress of any medications in use.

Treatment for irregular sleep–wake rhythm tries to enable the body clock in the brain, such that a normal long sleep period at night can be achieved. Education about sleep hygiene is important, and counseling can be helpful. Melatonin, vitamin B, sleep aids, wake aids, and other medications may also be used. Light during the daytime, and activities occurring at regular times each day, may help to restore a normal rhythm.

Because there are different systems in the body that help establish regulation, it's helpful to employ a multi-modal approach. A 2008 review states that "...each clock is differentially sensitive to zeitgebers. The suprachiasmatic nucleus (SCN) is very responsive to light, the clock in the liver is very sensitive to food, and clocks in muscle are sensitive to exercise."

The following approaches are recommended by one source:

1. Spend <7–8 hours in bed.

2. Add environmental cues such as light and social interactions, regular meal times, and regular sleep–wake times.

3. Morning and eve light at 3000 lux for 2 hours have been shown to improve nocturnal sleep in institutionalized patients and reduce agitation in demented patients.

4. Melatonin at desired sleep time.

For those whose RLS disrupts or prevents sleep or regular daily activities, medication may be useful. Evidence supports the use of dopamine agonists including: pramipexole, ropinirole, rotigotine, and cabergoline. They reduce symptoms, improve sleep quality and quality of life. Levodopa is also effective. One review found pramipexole to be better than ropinirole.

There are, however, issues with the use of dopamine agonists including augmentation. This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also cause rebound when symptoms increase as the drug wears off. In many cases, the longer dopamine agonists have been used the higher the risk of augmentation and rebound as well as the severity of the symptoms. Also, a recent study indicated that dopamine agonists used in restless leg syndrome can lead to an increase in compulsive gambling.

- Gabapentin or pregabalin, a non-dopaminergic treatment for moderate to severe primary RLS

- Opioids are only indicated in severe cases that do not respond to other measures due to their high rate of side effects.

Benzodiazepines, such as diazepam or clonazepam, are not generally recommended, and their effectiveness is unknown. They however are sometimes still used as a second line, as add on agents. Quinine is not recommended due to its risk of serious side effects involving the blood.