Sign Up It's Free! If you log out, you will be required to enter your username and password the next time you visit. Brand and Other Names: Share Email Print Feedback Close. Essential Tremor Off-label 0. Burning Mouth Syndrome Off-label 0. Dosage Modifications Renal impairment: Supplemental dose in hemodialysis not necessary. Dosing Considerations Discontinuation of treatment: Significant - Monitor Closely. All Interactions Sort By: Frequency Not Defined Increased salivation Worsening tonic-clonic seizures.
Warnings Black Box Warnings Concomitant use of benzodiazepines and opioids may result in profound respiratory depression, coma, and death; administer concomitantly when there are no alternative options; limit dosages and durations to minimum required; monitor for signs and symptoms of respiratory depression and sedation.
Contraindications Significant hepatic impairment Documented hypersensitivity Acute narrow angle glaucoma. Lactation Effects on breastfed infant and on milk production are unknown; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition. Pharmacology Mechanism of Action Long-acting benzodiazepine that increases the presynaptic GABA inhibition and reduces the monosynaptic and polysynaptic reflexes.
Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters Suppresses the spike-and-wave discharge in absence seizures by depressing nerve transmission in motor cortex. Print without Office Info. Print with Office Info. Formulary Formulary Patient Discounts. Create Your List of Plans. View explanations for tiers and restrictions. Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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Non-benzodiazepines appear to have lower abuse potential at recommended dosages, but may still have a significant risk at higher doses. The longer acting agents eszopiclone and zolpidem CR are effective for the treatment of sleep maintenance problems as well as sleep initiation. These are the only agents other than benzodiazepines that are currently FDA approved for the treatment of both sleep onset and sleep maintenance problems. Melatonin is an endogenous hormone produced by the pineal gland that is intimately involved in circadian rhythms.
Two melatonin agonists are currently available in the U. Unlike benzodiazepines and non-benzodiazepines, the sleep enhancing effects of melatonin agonists have not been found to vary with dose. Ramelteon is melatonin receptor agonist MT1 and MT2 that was introduced in It has a strong affinity for the MT1 receptor which is believed to regulate drowsiness by dampening wake promoting signals from the SCN. Drug Enforcement Administration DEA as having a significant potential for abuse the other being doxepin.
Exogenous melatonin is available as a supplement that is not regulated by the FDA and is therefore available in a wide range of doses. Controlled studies have not found it to have substantive therapeutic effects in insomnia patients. Most studies have evaluated a dose of 8 mg administered 30 minutes prior to lights out. The effects have been limited to improvements in sleep onset latency with larger effects shown by polysomnography than by subjective measures of sleep. The most commonly reported side effects were headache, somnolence and sore throat, but these were not significantly elevated relative to placebo.
Ramelteon and melatonin have favorable profiles of adverse effects and no significant potential for abuse although they have not been studied in populations at high risk for substance abuse. The most common adverse-effects of melatonin are headache, sedation and slowed reaction times. Ramelteon has also been associated with somnolence, dizziness, nausea and fatigue, but no effects on fertility have been reported.
It has also been found to be safe for use in patients with mild to moderate sleep apnea 51 and moderate to severe obstructive pulmonary disease. H1 antagonists are believed to exert therapeutic effects on sleep by blocking the wake promoting effects of histamine. Both medications have similar properties and the usual dose for each is 2550 mg. Both have significant muscarinic cholinergic antagonist effects that are believed to contribute to their effects on sleep and be the primary source of side effects.
There have been no placebo-controlled trials in insomnia patients to evaluate the safety or efficacy of doxylamine, but a few exist for diphenhydramine. Doxylamine has only been evaluated for the treatment of insomnia in one large double-blind trial of postoperative patients. Results indicated a significant benefit on subjective measures of sleep. The only selective H1 antagonist that has been studied for the treatment of insomnia is Doxepin, a tricyclic antidepressant which has FDA approval for the treatment of depression in dosages from 75 mg and for the treatment of insomnia in dosages from 36 mg.
As with diphenhydramine, low-dose doxepin has stronger effects on sleep maintenance than it has on sleep onset. The therapeutic effect on sleep maintenance has been demonstrated for both younger and older adults and it is FDA approved for treating sleep maintenance but not sleep onset problems. The most common adverse-effects associated with antihistamines are anticholinergic effects such as dry mouth, blurred vision, constipation, urinary retention, and delirium, and should therefore be avoided in patients at risk for complications due to anticholinergic effects, such as those with dementia, urinary retention and narrow-angle glaucoma.
Other adverse effects include sedation, dizziness and weight gain. Less frequent side-effects of diphenhydramine include agitation and insomnia. Case reports have suggested that doxylamine may be associated with coma and rhabdomyolysis. The benefits for allergies make antihistamines particularly well-suited to insomnia occurring with allergies or nasal congestion. Antidepressants are often used in the treatment of insomnia, but relatively little data exist on their efficacy and safety when used for this purpose.
Because of the paucity of placebo-controlled trials with these agents, their use cannot be recommended except in those individuals who fail or for some reason are precluded from the usual treatments. Antidepressants are typically prescribed at lower doses for the treatment of insomnia than for the treatment of major depression. These agents enhance sleep through antagonism of wake promoting systems including serotonin, norepinephrine, acetylcholine and histamine, though the relative degree of these effects differs among the antidepressants.
We will review the pharmacology and limited evidence base for those agents including doxepin dosages above 6 mg , amitriptyline, and trimipramine tricyclic antidepressants as well as, trazodone and mirtazapine. These agents promote sleep by antagonism of norepinephrine, histamine, and acetylcholine, all of which are involved in maintaining wakefulness and arousal. Most of data on the sleep effects of these agents come from trials of patients with major depression. Trimipramine dosed at 50 mg has been found to improve sleep quality and sleep efficiency, but not sleep onset latency.
Findings from these studies support its efficacy for improving sleep quality, sleep onset and sleep maintenance. These are all dose-dependent side-effects derived from anti-histaminergic, anti-cholinergic, anti-serotinergic, and anti-adrenergic effects. The abuse potential for tricyclic antidepressants is negligible so these agents may be useful in the treatment of insomnia among patients at high-risk for substance abuse.
In addition, they may be useful in treating insomnia in the context of comorbid conditions such as anxiety disorders or chronic pain. The safety and efficacy of combining these agents with non-sedating antidepressants is also unknown, so better established combined treatments are generally preferred. Finally, these agents must be prescribed with great caution in those at risk for suicide as they can be lethal in overdose.
Despite a relative lack of controlled trials demonstrating efficacy for insomnia, trazodone has been among the most frequently administered treatments for insomnia over the last 20 years. Trazodone is metabolized into a wake-promoting molecule methyl-chlorophenylpiperazine or mCPP to a highly variable degree due to a genetic polymorphism that is not rare in the population. It is helpful to inform patients about this possibility prior to prescribing the medication. Genetic polymorphisms that affect the metabolism of trazodone into an active, sedating, metabolite and the elimination of that metabolite also exist.
As a result, some individuals experience prohibitive daytime sedation with this agent. Given its frequency of use, it is perhaps surprising that there has been only one placebo-controlled study of trazodone for insomnia. The group receiving active medication reported better sleep than placebo treated subjects for the first week, but there were no differences between groups in the second week of treatment. Two smaller placebo-controlled studies, one in abstinent alcoholics and another in patients with major depression, 78 , 79 reported sleep-promoting effects of trazodone, but did not evaluate in the treatment of insomnia per se.
The most common adverse effects associated with trazodone are sedation, dizziness, headache, dry mouth, blurred vision and orthostatic hypotension. The small placebo-controlled trial in abstinent alcoholics did not show any problems with abuse of the medication. Preliminary evidence suggests that it can be safely used to treat insomnia in conjunction with fluoxetine and buproprion but its use with other antidepressants has not been evaluated. While the range for antidepressant dosing is 7.
There have been no placebo-controlled trials of mirtazapine for the treatment of insomnia. The evidence that mirtazapine may benefit sleep comes from a double-blind evaluation of mirtazapine vs. Based on trials treating major depression, the most common side effects associated with mirtazapine are sedation, increased appetite, weight gain, dry mouth, and constipation. Because of the overlap in dosages used to treat insomnia and depression, mirtazapine can be considered for single-agent therapy for those with insomnia and co-morbid depression.
Future studies will be needed to evaluate this agent's effectiveness relative to combining a non-sedating antidepressant with an established insomnia therapy. The antipsychotics most commonly used to treat insomnia are quetiapine dosed at 25 mg and olanzapine dosed at 2. Quetiapine on the other hand has a tmax of 12 hours and a half-life of 7 hours 3 making it well suited for both sleep onset problems and sleep maintenance problems.
No placebo-controlled trials have been completed with these agents for the treatment of insomnia specifically, therefore the risk-benefit profile is difficult to assess. Evidence for a sleep enhancing effect of quetiapine 2575 mg was reported from open-label studies with primary insomnia patients and with healthy volunteers 87 while olanzapine has been noted to enhance sleep in an open-label study of healthy volunteers only.
The most common side-effects associated with antipsychotic agents in the treatment of insomnia are sedation, dizziness, anticholinergic side-effects dry mouth, blurred vision, constipation, urinary retention , and increased appetite, 86 with some agents having better side effect profiles than others. Other potential side-effects associated with dopamine antagonism can result as well, including parkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia.
Olanzapine has been found to increase risk of insulin resistance, impaired cognition and mortality in dementia patients. All of these agents should be used with caution in older adults due to increased risk of cardiac-related mortality. Antipsychotic agents are not generally used in patients with insomnia who do not have a co-occurring psychotic or mood disorder, but may be particularly useful in this population. In addition to the effects mentioned above, many of these agents have mood stabilizing properties useful in the treatment of mania.
Quetiapine is also FDA approved for the treatment of depression. Antipsychotic agents can also be considered for use in abuse-prone patients with insomnia due to their low abuse potential. Anticonvulsants such as gabapentin, pregabalin and tiagabine, are sometimes used in the treatment of insomnia. Gabapentin and pregabalin bind to the alphadelta subunit of N-type voltage-gated calcium channels, which decreases the activity of wake promoting glutamate and norepinephrine systems.
Tiagabine enhances sleep by inhibiting the reuptake of GABA. Gabapentin and pregabalin have been demonstrated to have sleep enhancing effects in a variety of populations including healthy volunteers, patients with restless legs syndrome, chronic pain patients and patients with partial seizures. The most common side effects associated with gabapentin are ataxia and diplopia, while pregabalin is associated with dry mouth, cognitive impairment, peripheral edema and increased appetite.
Tiagabine is most commonly associated with nausea. Of these medications, only pregabalin is associated with abuse potential and should be used with caution in patients who are prone to substance abuse. For insomnia that is comorbid with pain, gabapentin and pregabalin may be particularly useful. Pregabalin should be considered in the treatment of insomnia in fibromyalgia patients because available evidence suggests it is effective for both conditions.
Preliminary evidence also suggests that gabapentin may be indicated for patients with restless legs syndrome and periodic movements of sleep. Prazosin is an antihypertensive medication with relatively recently discovered benefits for sleep, primarily in those who experience frequent nightmares and sleep disturbance associated with post-traumatic stress disorder PTSD. The recommended starting dose is 1 mg to prevent hypotension, then the dose is slowly titrated upward until a therapeutic effect is achieved.
Placebo-controlled trials have reported benefits of prazosin in the treatment of sleep disturbance and trauma-related nightmares in military veterans and civilians with PTSD. Improvements in self-reported symptoms associated with prazosin include nightmare frequency, insomnia severity, and PTSD symptom severity; home-PSG-measured symptom improvement has also been found for total sleep time, REM sleep time, and REM duration.
Prazosin has been found to be well tolerated in all trials to date. Although studies to date have not been powered to detect adverse-effects in prazosin relative to placebo, the following symptoms have been reported in the trials listed above: Prazosin is the only sleep-enhancing agent shown to reduce sleep impairment due to nightmares and is therefore particularly useful in sleep disturbances associated with PTSD.
As reviewed in the previous section, the medications used to treat insomnia differ as to the time of night during which they have been established to have therapeutic effects. Some have been found only to improve problems with sleep onset, some have reliable therapeutic effects on sleep maintenance without onset effects, and some have reliable effects on both onset and sleep maintenance.
Among those with sleep maintenance effects some agents have these effects to the end of the night while others do not. The time of night during which sleep problems occur differs among insomnia sufferers. Treatment optimization therefore depends on selecting a medication that has therapeutic effects at the time of night during which an individual's sleep problem occurs. In the following discussion we review how to match the choice of medication to the patient's specific type of sleep problem.
For those who have difficulties falling asleep without difficulties staying asleep, the optimal strategy is to choose a medication which has been demonstrated to have therapeutic effects on sleep onset with the least associated adverse effects. This includes those agents which have been demonstrated to have therapeutic effects on sleep onset without having effects on sleep maintenance. Any of these might be appropriate for treating a patient with sleep onset difficulties.
However, optimizing the choice among these agents requires considering the patient's past history with medications have they failed to improve with one or more of these agents in the past? Did they have problems with side-effects with one or more of these agents in the past? Although not a factor related to optimizing the matching of medication to the patient's sleep problem, cost may affect what medication can practically be obtained or which is tried first.
If any of the above factors precludes the use of all 3 of the medications best-suited for treating those with sleep onset problems listed above, the following agents which have been demonstrated to have therapeutic effects on both sleep onset and sleep maintenance could be considered for second line use with the understanding that they are likely to have a greater risk of adverse effects. For those who have difficulties staying asleep without difficulties falling asleep, the optimal strategy is to choose a medication which has been demonstrated to have therapeutic effects on sleep maintenance with the least associated adverse effects.
This includes the agents which have been demonstrated to have therapeutic effects on sleep maintenance without having effects on sleep onset. For those individuals who have difficulties in the last 2 hours of the night, the only option is doxepin 3,6 mg as described above. If factors such as prior experience with the medications, temporal pattern of the sleep problem, co-morbidities or cost factors precludes the use of all 3 of the medications listed above, the following agents which have therapeutic effects on both sleep onset and sleep maintenance could be considered for second line use with the understanding that they are likely to have a greater risk of adverse effects.
A final consideration is that doxepin is the only agent demonstrated to have therapeutic effects in the last 2 hours of the night without substantively increasing the risks of daytime impairment. A subset of the agents used in the treatment of insomnia have been demonstrated to have therapeutic effects in patients with both sleep onset and sleep maintenance problems.
In those with difficulties in the last 2 hours of the night, the only option is to use doxepin to address this end of the night problem and combine it with an agent with therapeutic effects only for sleep onset problems such as:. The need to administer two medications in this circumstance due to the absence of a single medication that improves sleep at the end of the night and also improves sleep onset suggests an unmet need in the field of insomnia.
Another factor that is necessary to consider in the optimization of the medication management of insomnia is the patient's temporal pattern of sleep difficulties over nights. Some individuals have their problems nightly, whereas others have their problems intermittently. Among those with intermittent insomnia, their problem can occur anywhere from rarely to nearly every night.
The temporal pattern has important implications for determining the optimal strategy for medication management. For patients with nightly difficulties falling asleep, nightly administration of an agent targeting sleep onset is generally indicated See 3. However, a challenge that arises is that nightly use of an effective sleep medication may make it difficult to determine if the insomnia ceases at some point such that the medication is no longer needed.
This situation can make both patients and prescribers uncomfortable because it raises the possibility that once treatment with a sleep medication begins, it continues indefinitely. Further contributing to this problem is the concern that rebound insomnia occurring with discontinuation after a period of nightly use may falsely reinforce a sense of an ongoing need for nightly medication. Notably, a substantial number of relatively recent studies have indicated that significant rebound insomnia did not occur with nightly treatment for: Without systematic data collection, such experiences can create the perception among clinicians that rebound insomnia is nearly universal.
This can lead practitioners to avoid treating patients with nightly insomnia with medications or to require that their patients use the medications non-nightly. In our experience, the most effective means for addressing this challenge is to have an a priori strategy for stopping medications in those with nightly sleep problems. The most effective strategy has been to agree, prior to starting medications, that after a fixed period of time, typically 3 months, a trial medication taper will be instituted.
This taper is nearly always effective in allowing patients to discontinue medications if they are warned to expect a transitory worsening of sleep following medication discontinueation and and if the taper is carried out slowly enough. Once the patient has discontinued use of the medication, an assessment can be made about whether the patient was better off using the medication or not using the medication.
If the former is the case, the medication is re-started with a plan to institute another trial taper in 3 months. If the latter turns out to be true, the medication is discontinued. This type of exit strategy tends to make both patients and prescribers less anxious about the nightly use of medications for insomnia in those with nightly sleep problems and ensures that medication use will persist for roughly the period that it is needed.
All three of the medications which have been reported to have therapeutic effects on sleep onset without effects on sleep maintenance, ramelteon, zaleplon, and zolpidem, have all been demonstrated to be safe and effective for at least 6 months of nightly treatment and could all be used in individuals with nightly difficulties falling asleep. There are two options for treating patients with problems staying asleep. One is to administer a medication at bedtime in an attempt to prevent the awakening from occurring.
The other is to have the patient take a medication if they wake up in the middle of the night in order to speed the return to sleep. When the problem with middle of the night awakenings occurs on a nightly basis, however, the best strategy is to take medication nightly at bedtime to prevent the awakening from occurring, rather than having to suffer from awakening nightly and then having to wait for the medication to take effect.
If nightly sleep maintenance problems occur in the absence of problems falling asleep, doxepin, which has been demonstrated to be efficacious and safe in 3 months of nightly use could be used. If both problems falling asleep and staying asleep are present, then the best choice from the point of view of long-term safety and efficacy is eszopiclone. As with nightly onset problems, when prescribing these medications nightly it is necessary to have a plan for stopping the medication such as instituting periodic trial medication tapers.
When trouble falling asleep occurs intermittently, the optimal treatment strategy depends on whether the affected individual is able to tell prior to going to bed whether they are likely to have a bad night. In those able to predict difficulties falling asleep, medication therapy can be administered on nights when problems are anticipated. Where prediction isn't possible, one option is to have patients try to sleep and then take a medication if they fail to do so.
However, for patients prone to developing a worsening of insomnia if they if they have nights wherein they try to sleep and fail, then this strategy is best avoided and implementation of cognitive behavioral insomnia therapy should be considered. For those with difficulty staying asleep occurring nightly or nearly nightly, nightly treatment at bedtime in an attempt to prevent the awakening is generally the best strategy.
However, for those with relatively infrequent difficulties waking up in the middle of the night, optimal treatment would involve providing an intervention to take in the middle of the night only on those nights when the awakening occurs. If it were possible to predict the nights where the middle of the night awakenings were most likely to occur, then a strategy of using a medication prior to bedtime to prevent those awakenings would be optimal.
However, these awakenings are generally not predictable at bedtime. As a result, the strategy of taking a medication in the middle of the night has the substantial advantage over nightly bedtime dosing in that it only requires medication use on nights when the sleep problem occurs, thereby reducing the number of nights medication is used.
This strategy decreases the cost and associated risks of the medication used. Data demonstrating that this strategy can be employed effectively and safely have been reported for sublingual zolpidem Intermezzo and zaleplon when these are taken up to 4 hours before getting out of bed in the morning. There are no studies demonstrating the safe and effective use of a medication for a middle of the night awakening that occurs less than 4 hours before getting out of bed. As a result, this sort of practice cannot be recommended.
This consideration is highly important since patients with co-morbid medical and psychiatric conditions constitute the majority of patients with insomnia. As a result, failure to consider the presence of such co-morbidities can result in suboptimal or adverse treatment outcomes. The following discussion provides guidance for optimizing treatment for those co-morbid conditions for which the most data are available and which are most commonly associated with insomnia.
These include major depression, generalized anxiety disorder, post-traumatic stress disorder, chronic pain, and alcoholism. The long-standing view of insomnia occurring in those with major depression has been that insomnia is a secondary symptom of the depression that does not merit specific treatment. It was assumed that effective antidepressant therapy would eliminate insomnia just as it improves other symptoms of depression.
However the available data clearly indicate that this view is incorrect and speak to the need to provide insomnia-targeted treatment along with administering antidepressant therapy. As described above, five studies have been carried out in which patients with insomnia co-morbid with major depression were treated with an antidepressant medication along with an agent used in the treatment of insomnia or placebo.
These studies provide some support for the utility of adding clonazepam to selective serotonin reuptake inhibitor therapy in patients with depression and insomnia. Sleep was improved in 3 of the studies conducted and in two it was associated with greater improvement in depression symptoms. In all three studies carried out with clonazepam, this agent improved sleep and in two it was associated with greater improvement in depression symptoms, though it appears that with longer duration of treatment the improvement in depression symptoms with clonazepam may not be sustained.
A study of patients with insomnia and rheumatoid arthritis reported a benefit of triazolam relative to placebo for both sleep and morning. As described above, a study in which patients with insomnia and co-morbid depression were randomized to receive eszopiclone or placebo along with fluoxetine indicated that eszopiclone improved not only sleep but also was associated with more rapid and greater improvement in depression symptoms sleep items were removed from the depression rating scale.
In terms of single agent therapy, a few placebo-controlled studies have assessed the therapeutic sleep effects of antidepressants a small study of tricyclic antiderpessants and one study of mirtazapine in therapeutic antidepressant dosages in patients with co-morbid insomnia and depression. Overall, the available data most strongly suggest the use of eszopiclone along with a non-sedating antidepressant for initial therapy of those with insomnia co-morbid with major depression.
Although it should be noted that data exist only for combining eszopiclone with fluoxetine, and it remains unknown whether similar effects would be seen with other antidepressants. Clonazepam could be considered for use in these patients but the relatively higher risk of daytime sedation and possibility of loss of antidepressant benefit over time suggests that it should be reserved for second tier use. Zolpidem CR could also be considered, though eszopiclone would be preferred due to the relatively greater benefit on depression symptoms.
Lastly, employing single-agent therapy with mirtazapine is also a supported option. Data are needed to evaluate the utility of single-agent therapy with mirtazapine vs. Another consideration relevant to those with depression and co-morbid insomnia is the choice of treatment when an individual is treated with an antidepressant and improves but has sustained insomnia which has not been treated. Studies have been carried out trazodone and zolpidem for this circumstance.
On the basis of these studies, zolpidem and perhaps trazodone could be considered for patients with insomnia who have remitted to non-sedating antidepressant therapy. As with major depression, it has long been assumed that it was not necessary to administer insomnia-specific treatment in those with generalized anxiety disorder GAD. However, relatively recent guidelines recommend administering insomnia targeted therapy along with anxiolytic therapy in those with GAD.
However, based on available data, eszopiclone would be the treatment of choice when adding a sleep targeted therapy to treatment with a selective serotonin reuptake inhibitor. Zolpidem CR could also be considered for improving sleep but should be considered as a second choice based on the lesser improvement in anxiety symptoms.
Few studies have been carried out on the pharmacologic treatment of sleep problems occurring in the setting of post-traumatic stress disorder PTSD. As reviewed in section 2, the only agents that have been evaluated in placebo-controlled trials are eszopiclone and prazosin. Eszopiclone improved both sleep disturbance and PTSD symptoms in a cross-over study conducted with 24 patients. Eszopiclone should also be considered for use in in these patients based on the small cross-over study carried out.
The available evidence suggests that individuals with insomnia occurring co-morbid with chronic pain are best treated by administering both pain-targeted and insomnia-targeted therapies. Triazolam was found to improve sleep and morning stiffness in those with rheumatoid arthritis 7 and eszopiclone led to improvement in sleep and some pain ratings in this same population. However, they indicate that eszopiclone has potential as a sleep-targeted therapy in this setting and triazolam could also be considered.
Studies with other insomnia medications are needed to establish whether the therapeutic effects seen in pain patients are specific to eszopiclone and triazolam or would be seen with other medications. The pharmacologic treatment of sleep problems occurring in patients with alcoholism have been the subject of little research. As reviewed above, only one small placebo-controlled trial with trazodone has been found to have therapeutic effects on sleep in patients with alcoholism recently abstinent.
Trazodone which appears to have minimal abuse potential should be considered in this population but more studies are needed with agents without significant abuse potential to help guide the management of insomnia in patients with alcoholism. As should be evident from the review above, there is a need for more studies aimed at identifying how to optimally manage patients with insomnia, particularly among patients with co-morbid conditions.
Additional studies are also needed to define how to best manage patients with nightly sleep onset problems. Although agents with established therapeutic effects on sleep onset and sleep maintenance are available for use in clinical practice, a need remains for the development of new agents that have therapeutic effects at the end of the night without increasing the risks of daytime sedation and that have this effect along with a therapeutic effect on sleep onset. Two agents in development are worthy of note in this regard.
One is the S-isomer of the antidepressant mirtazapine discussed above. This agent has a comparable pharmacologic profile as the racemate with predominant, highly potent, and selective H1 antagonist effects. Based on its pharmacology, this agent administered in relatively low dosages as have been evaluated would be expected to have similar properties to the selective H1 antagonist doxepin. Preliminary data from 4 placebo controlled studies have been presented with S-mirtazapine and they suggest that this is essentially the case, though effects on sleep onset may be more evident.
These studies suggest that S-mirtazapine has consistent therapeutic effects on sleep maintenance, and tends to have therapeutic effects on sleep onset, though these effects are not as large or consistent and are dose-dependent. Preliminary data from several trials suggest that this agent has therapeutic effects on sleep onset and maintenance including in the last third of the night and has sustained therapeutic effects with long-term nightly use without significant withdrawal or rebound insomnia upon discontinuation and overall appears to have a favorable adverse effects profile.
These agents have the potential to add to the options that are available for providing individualized insomnia pharmacotherapy that best meets the needs of insomnia patients. The clinical availability of agents such as these and the completion of more studies to help define how to best tailor the choice of treatment for each patient promise to continue the steady evolution of the field towards greater capacity to select insomnia medications which optimize outcomes and thereby improve the treatment of the many who suffer from insomnia.
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National Center for Biotechnology Information , U. Author manuscript; available in PMC Sep 1. Jared Minkel , Ph. Krystal , MD, MS. Copyright notice and Disclaimer. See other articles in PMC that cite the published article. Abstract A number of medications are available for treating patients with insomnia. Introduction A number of different types of medications are currently available for the treatment of insomnia.
Type of Pharmacologic Treatment for Insomnia Available 2. Prescription agents approved by U. FDA for treatment of insomnia 2. Evidence base A number of controlled trials have established the efficacy of benzodiazapines for the treatment of insomnia. Non-Benzodiazapines Pharmacology The non-benzodiazepines include some of the most commonly prescribed sleep-promoting medications, including zolpidem, zaleplon, and eszopiclone.