Gabapentin, sold under the brand name “Neurontin,” is a drug that was first approved by the United States FDA in 1993 as an adjunct treatment for partial seizures in adults. Thereafter, gabapentin’s indication as a treatment for partial seizures would be extended in 2000 to pediatrics, and subsequently, it would receive FDA approval for the management of postherpetic neuralgia in 2002. Although solely approved for partial seizures and postherpetic neuralgia, it is frequently utilized as an off-label intervention for a host of medical conditions, including: anxiety disorders, bipolar disorder, chronic pain, hot flashes, migraine, neuropathic pain, and restless leg syndrome.
Though not commonly prescribed for the treatment of sleep-related medical conditions, numerous anecdotes from gabapentin users assert that the drug is highly effective as a sleep aid. Because a subset of persons with severe sleep disturbances find currently-available FDA-approved sleep medications (i.e. Z-drugs) intolerable and/or ineffective, it’s reasonable to question whether gabapentin could be useful as an alternative sleep aid. Preliminary evidence indicates that gabapentin can attenuate insomnia, bolster sleep quality, and increase total sleep duration.
Moreover, gabapentin has been shown to increase slow-wave sleep (SWS), promote sleep maintenance, and decrease unwanted awakenings throughout the night. Although preliminary evidence supports the idea that gabapentin can favorably modulate aspects of sleep, [and it makes logical sense that this would occur given its inhibitory effect upon physiology], further research is needed before off-label usage of gabapentin for sleep-related conditions is justified. Nonetheless, if you’re already using gabapentin for sleep and/or insomnia, it may be helpful to understand how it works and all potential benefits/risks associated with its administration.
Gabapentin for Sleep & Insomnia: Ways It May Help (Possibilities)
There are many ways in which gabapentin administration may enhance sleep and/or treat insomnia. That said, the specific way(s) in which gabapentin improves sleep and/or treats insomnia may be somewhat subject to individual variation. For example, someone with severe neuropathic pain may have developed sleep disturbances and/or insomnia as a result of the pain, yet after administering gabapentin, the neuropathic pain decreases and the sleep disturbances subside. Another example might be someone with anxiety who experiences insomnia due to uncontrollable worry prior to bed, yet after administration of gabapentin, the uncontrollable worry abates – as does the corresponding insomnia. Included below is a comprehensive list of ways in which people may perceive gabapentin as working to improve sleep.
- Agitation reduction: Certain individuals may experience insomnia and/or sleep disturbances due to uncontrollable bouts of agitation characterized by internal sensations of nervousness, excitement, and/or restlessness. If you feel agitated before bed, this may be due to excessive production of excitatory neurotransmitters and hormones, as well as corresponding activation of the sympathetic nervous system. As a result, persons with agitation may find it difficult to fall asleep and/or stay asleep throughout the night [due to excessive tossing and turning]. Because gabapentin facilitates an inhibitory effect upon neurotransmission and attenuates excessive sympathetic tone, it’s often helpful for reducing agitation. Assuming gabapentin mitigates agitation, any sleep disturbances stemming from that agitation should subside while under its influence.
- Anxiolytic effect: A major cause of sleep disturbances and insomnia is unmanaged anxiety. When unmanaged, anxiety alters neurotransmitter production and hormone secretion to maintain activation of the sympathetic nervous system. This can lead to physical symptoms of anxiety such as headache, heart palpitations, restlessness, skin tingling, and sweating – which generally exacerbates psychological symptoms of anxiety such as accelerated thinking, rumination, and uncontrollable negative thoughts. Because gabapentin inhibits excessive CNS activation, this can decrease physical sensations and psychological patterns implicated in anxiety enough to mitigate anxiety-induced insomnia and/or sleep problems. For more information regarding gabapentin’s anxiolytic effect, read: “Gabapentin for Anxiety Disorders.”
- Excitement mitigation: It’s possible to struggle with insomnia and/or sleep disturbances due to constantly feeling excited. The underlying physiologic activation associated with excitement is relatively similar to that of anxiety. Although excitement is generally considered a positive emotion and anxiety a negative one, each involve upregulation of the sympathetic nervous system and secretion of excitatory neurotransmitters plus hormones. The ongoing administration of gabapentin should help mitigate excitement through its central inhibitory action, thereby ameliorating excitement-induced sleep disturbances.
- Headache or Migraine reduction: A subset of the population may experience sleep problems stemming from uncontrollable headache or migraine. Headache or migraine-induced sleep problems are problematic in that they create a vicious circle in which the sleep disturbances they induce end up increasing future likelihood of headache or migraine, which in turn, deleteriously affect sleep. While gabapentin is not approved for the treatment of headaches and/or migraines, some claim that it reduces the occurrence and/or severity of headache or migraine, which could significantly improve sleep.
- Mood stabilization: Another possible cause of insomnia and/or sleep disturbances is an unstable mood. Unexpected mood swings (such as occurs in bipolar disorder) or emotional fluctuations may interfere with both sleep onset and maintenance. Persons experiencing mania and/or hypomania may exhibit such marked excitatory physiologic activity, that it becomes seemingly impossible to get a good night’s sleep. At the opposite end of the mood spectrum, some individuals dealing with major depression often struggle with sleep issues. Gabapentin may serve as an effective mood stabilizer for a subset of individuals, and because of the mood stabilization, it becomes easier to get a good night’s sleep.
- Muscle relaxant: When muscles are tense and/or rigid, it is typically challenging to fall asleep and get quality sleep. Muscle tension is often associated with excess activation of the sympathetic nervous system and unmanaged anxiety, however, it is also a result of various degenerative conditions such as multiple sclerosis. Many persons with muscle tension know that if there were a way to relax their muscles, they’d have no problem getting a good night’s sleep. Despite the fact that gabapentin is not technically classified as a muscle relaxant, it is sometimes used to treat muscle spasticity (tightness and/or stiffness), suggestive of the fact that it could relax the muscles to improve sleep among persons with muscle tension-induced sleep disturbances.
- Pain reduction: Gabapentin is approved for the treatment of neuropathic pain, a condition in which nerve fibers are damaged, dysfunctional, and/or injured – and end up transmitting improper signals to pain centers. Anyone with neuropathic pain may struggle to fall asleep at night and/or stay asleep due to the severity of the pain sensations. Managing preexisting neuropathic pain with gabapentin should help reduce sleep disturbances associated with unmanaged neuropathic pain. Moreover, among some persons with chronic pain conditions who struggle to sleep from the incessant pain sensations, gabapentin may reduce the pain enough to get a good night’s sleep.
- Restless leg syndrome (RLS): There’s evidence to suggest that gabapentin can treat moderate-to-severe idiopathic restless leg syndrome. Restless leg syndrome is a condition in which sufferers experience sensations throughout the legs that induce urges and/or compulsions to move the legs. Persons with RLS often report that their symptoms are worst in the evening and/or before bed which leads to sleep disturbances. In the event that an RLS sufferer derives benefit from gabapentin, it’s reasonable to think that the reduction of restless leg would improve sleep.
- Sedative effect: Among the most common side effects reported by gabapentin users is sedation. Sedation occurs largely due to the fact that gabapentin exerts an inhibitory effect upon physiology whereby excitatory transmission and sympathetic nervous system activity decrease. This sedation allows for a smoother transition from wakefulness to sleep and is thought to augment sleep maintenance. Even among persons who don’t usually experience agitation, anxiety, and/or hyperexcitability – the sedative effect induced by gabapentin may be perceived as conducive to the enhancement of sleep.
- Serenic effect: It’s common knowledge that pent up aggression, irritability, and/or anger can cause insomnia and disturb sleep. Persons with a history of unmanaged aggression and/or irritability may find that gabapentin effectively treats aggression and promotes a sense of internal peace or calm. In the event that gabapentin quells a person’s aggressive impulses through its inhibitory effect, most would suspect that their sleep might improve.
- Treating withdrawal symptoms: Another reason many individuals experience insomnia and irregular sleep is due to discontinuation of a psychoactive drug. Withdrawal from any psychoactive substance generally leaves aspects of a person’s CNS imbalanced – including neurotransmission, hormone signaling, and autonomic activation – each of which can interfere with sleep. Moreover, specific symptoms of withdrawal such as heart palpitations may trigger such extreme anxiety, that it becomes impossible to sleep. Because gabapentin can attenuate symptoms of withdrawal from many psychoactive drugs, its usage among persons subject to withdrawal may improve their sleep. (For further information, read: “Gabapentin for Opiate Withdrawal”).
Note: The above ways in which individuals may attribute the administration of gabapentin as leading to sleep improvement may be incomplete. If you know of another way in which gabapentin may lead to better sleep, share it in the comments section below. Moreover, it should be mentioned that some individuals may derive sleep enhancement from gabapentin through multiple of the aforestated ways. For example, someone diagnosed with anxiety and RLS may find that gabapentin treats both conditions simultaneously to enhance sleep.
Benefits of Using Gabapentin for Sleep (Possibilities)
There are many potential benefits to be attained from the usage of gabapentin for sleep. Perhaps the most substantial benefit is that gabapentin may prove effective as a sleep aid for individuals with refractory sleep disturbances who don’t respond to first-line hypnotics. Other benefits associated with the usage of gabapentin for sleep include its: ability to treat comorbid medical conditions, favorable effect on sleep architecture, low cost, preliminary scientific support as a sleep aid, and tolerability.
- Adjunct option: It is common for individuals with sleep disturbances to have other medical conditions requiring regular pharmacological treatment. Emerging evidence suggests that gabapentin can be administered along with certain medications as an adjunct sleep aid. For example, a randomized controlled trial discovered that adjunct gabapentin (100 mg to 600 mg) attenuates unremitting insomnia among persons taking SSRIs for major depression. A case report revealed that adjunct gabapentin treated refractory insomnia among a person with bipolar disorder who had been taking 2 other medications. Moreover, there are numerous other medications with which adjunct gabapentin may facilitate sleep enhancement.
- Alternative sleep aid: Certain individuals derive insufficient benefit from first-line hypnotics for the treatment of sleep disturbances. Others may find that they cannot tolerate the side effects of first-line hypnotics or that the side effects interfere with occupational performance (e.g. drowsiness). For persons who are unable to benefit from and/or tolerate conventional hypnotics, gabapentin may serve as a more effective and/or tolerable alternative. Most preliminary evidence suggests that, when the dosage is properly calibrated, gabapentin is effective and very tolerable as a sleep aid.
- As-needed administration: Another benefit of using gabapentin as a sleep aid is that it appears effective when administered on an “as-needed” basis. While individuals who use gabapentin for the treatment of chronic conditions (e.g. postherpetic neuralgia) typically require regular administration (e.g. 3 times per day) for sustained symptomatic relief, persons using gabapentin as a sleep aid respond well to once nightly (q.h.s.) administration. Moreover, the hypnotic efficacy of gabapentin doesn’t appear to diminish if the user fails to take the drug every day. Perhaps the most substantial benefit with once-nightly and/or as-needed administration of gabapentin is that it may: reduce and/or prolong tolerance onset, minimize odds of deleterious long-term effects, and decrease likelihood of severe withdrawal symptoms following cessation.
- Comorbid medical conditions: In addition to treating a sleep disorder, gabapentin may address comorbid medical conditions. As many individuals are aware, gabapentin is FDA approved for the treatment of postherpetic neuralgia and partial onset seizures (as an adjunct). Persons with either of the aforestated conditions plus comorbid sleep disturbances may find that gabapentin treats both simultaneously. Other medical comorbidities that gabapentin may treat while simultaneously attenuating sleep disturbances include: anxiety, bipolar disorder, depression, fibromyalgia, neuropathic pain, RLS, and substance dependence. Many may like the idea of using standalone gabapentin to manage sleep plus another medical condition due to the fact that it’s simpler than using a different pill for each.
- Evidence-based: Not only are there numerous anecdotes from gabapentin users claiming that the drug improves sleep, there’s also evidence from a multitude of trials and case studies supporting its efficacy as a sleep aid. In fact, data from all available trials and case studies are unanimous in suggesting that gabapentin treats sleep disturbances and/or enhances sleep quality. Because gabapentin’s usage for the management of sleep disturbances is based in evidence, there’s a greater chance that it’ll prove effective than non-evidence based interventions. Moreover, having some evidence that supports its hypnotic efficacy increases likelihood that a medical professional would prescribe gabapentin off-label for sleep.
- Low cost: Another benefit associated with using gabapentin as a sleep aid is that, as a generic drug, it’s relatively affordable. Most pharmacies retail 90 capsules of gabapentin at the 300 mg dose for $12 to $25. Comparatively, a 30-day supply of a patented brand name sleeping medication (e.g. Belsomra) costs between $295 and $330. Without an elite health insurance plan, most cannot afford the out-of-pocket expense to attain sleeping medications under patent, making gabapentin the more cost-effective intervention. Additionally, even when compared to a subset of generic sleeping medications (e.g. eszopiclone), gabapentin remains slightly cheaper.
- Monotherapy: Though adjunct gabapentin may be an efficacious intervention for sleep disturbances, most research supports its efficacy as a monotherapy. As a monotherapy, gabapentin administered at dosages between 600 mg and 1800 mg once per night yielded sleep improvements in a variety of populations. Using gabapentin monotherapy may be favorable in terms of side effects and/or long-term efficacy compared to administering multiple agents to help with sleep.
- Refractory sleep disturbances: Certain individuals have tried nearly every conventional nonpharmacological and pharmacological intervention for the treatment of sleep disturbances, yet they continue to occur. For example, someone with refractory insomnia may have tried adhering to a sleep schedule, avoiding electronics in the evening, blocking blue light, ceasing usage of all psychoactive substances, and testing multiple first-line hypnotics – yet he/she may still find it nearly impossible to fall asleep and/or stay asleep. Although it’s rare for someone to derive zero benefit from a combination of nonpharmacologic and first-line hypnotic interventions, it could happen. In this case, the individual may benefit from administration of a less conventional, yet evidence-supported medication with a unique mechanism of action like gabapentin.
- Scheduling: Many first-line hypnotics are classified as “Schedule IV” controlled-substances due to exhibiting potential for abuse, addiction, and/or dependence. Individuals who use hypnotics that are classified as controlled-substances generally require in-person non-electronic signatures from a medical professional to attain refills. Getting hand-written signatures for each refill can become costly for patients in that they end up paying for monthly follow-up appointments for a limited supply of their sleeping medication. Comparatively, gabapentin is not classified as a controlled-substance and is available as a normative prescription. This means it should be easier for patients to acquire refills without having to constantly visit the doctor for an in-person non-electronic signature.
- Sleep enhancement: Polysomnography data reveals that gabapentin improves a myriad of sleep parameters including: architecture, duration, efficiency, and quality.
- Architecture: Gabapentin appears to improve sleep architecture by increasing slow-wave sleep and decreasing fast-wave sleep. Specifically, EEG readings indicate that gabapentin increases delta-2 waves and theta waves in Stage 1 of sleep and decreases sigma waves Stages N2 and N3.
- Duration: Those who experience insomnia and/or frequent nighttime awakenings often struggle to maintain a healthy sleep duration. Among persons with preexisting sleep duration deficits, gabapentin appears to extend total sleep time by over 1-hour (on average).
- Efficiency: Sleep efficiency is the ratio of total time spent asleep (total sleep time) to the total time spent in bed. Individuals with sleep disturbances tend to exhibit low sleep efficiency, whereas persons with sleep disturbances exhibit high sleep efficiency (e.g. 85% to 90%+). Gabapentin has been shown to significantly increase sleep efficiency, possibly by attenuating insomnia and/or nighttime awakenings.
- Quality: Research suggests that gabapentin facilitates objective and subjective improvements in sleep quality. Objective improvements in sleep quality are evidenced by polysomnography recording and physiologic assay data collected from gabapentin users. It appears as though gabapentin: increases slow-wave sleep, decreases fast-wave sleep, favorably modulates transitioning between sleep cycles, reduces spontaneous arousal index, and increases heart-rate variability. Subjective improvements in sleep quality have been reported by gabapentin users in trials.
- Superiority: It’s reasonable to hypothesize that, when compared to conventional hypnotics for the treatment of sleep disturbances, gabapentin might be superior in terms of: abuse/addiction/dependence potential, tolerability, rate of tolerance onset, long-term effects, and/or [potentially] efficacy. Unlike gabapentin, many conventional hypnotics (e.g. non-benzodiazepines) exhibit high potential for abuse, addiction, and dependence (hence their formal scheduling as “controlled substances”) – making them more dangerous psychiatric drugs by comparison. Additionally, while users of first-line hypnotics frequently report deleterious side effects such as cognitive dysfunction, coordination deficits, and drowsiness upon waking – these may be less prevalent and/or severe among gabapentin users. Also worth mentioning is the fact that, when utilized over a long-term, benzodiazepines (and related compounds) have been linked to dementia whereas no such link has been established with gabapentin, possibly making it a safer drug for the long-term. Lastly, research suggests that gabapentin may be more effective than the drug trazodone for the treatment of sleep disturbances. Moreover, many patients who don’t respond well to first-line and second-line interventions for sleep often derive benefit from gabapentin.
- Tolerability: When administered specifically for the management of sleep disturbances, gabapentin seems to be a well-tolerated medication for most. Although a subset of users will experience unwanted side effects such as mild drowsiness upon waking and/or cognitive deficits, these typically emerge in early weeks of administration and subside over a longer-term as the physiology adapts to the drug. Furthermore, other users have reported experiencing zero noticeable side effects from the administration of gabapentin once per night. Even among those who experience a few side effects while using gabapentin for sleep, most find them to be of modest severity and relatively manageable.
- Unique mechanism of action: For those who’ve tried several conventional sleep medications yet found them ineffective and/or intolerable – it’s likely that the mechanism of action is to blame. Most conventional sleep medications are classified as nonbenzodiazepines in that they act via modulation of the GABA (gamma aminobutyric acid) system, typically via agonism of GABAA receptor subunits (e.g. 1A). Gabapentin is thought to act by modulating: voltage gated calcium channels, GABA synthesis, and NMDA receptor activation. Perhaps this atypical mechanism of action is more efficacious and/or tolerable for certain individuals than conventional hypnotics for the management of sleep disturbances.
Drawbacks of Using Gabapentin for Sleep (Possibilities)
While there are clearly potential benefits associated with using gabapentin for the treatment of sleep disturbances, there are many potential drawbacks that warrant discussion. Perhaps the most significant drawback is that gabapentin may provoke severe adverse reactions and/or induce [permanent] unwanted long-term effects in a subset of users. Other possible drawbacks to consider when using gabapentin for sleep include its: abuse potential, ineffectiveness, inferiority (to other medications), off-label status, side effect profile, withdrawal symptoms that emerge upon cessation.
- Abuse, addiction, dependence potential: Although gabapentin isn’t formally classified as a “controlled substance,” it’s fair to argue that it should be. When considering that pregabalin – the chemically-analogous successor to gabapentin – is a controlled-substance, and that gabapentin has emerged as a recreational intoxicant, it’s reasonable to suspect that gabapentin exhibits greater potential for abuse or misuse, addiction, and dependence than most uncontrolled prescription drugs. Moreover, research supports the idea that gabapentin is abused and/or leads to addiction and dependence in a subset of users. While the nightly administration of gabapentin for sleep may yield lower rates of abuse/misuse, addiction, and/or dependence than multiple-times-per-day administration and/or compared to conventional sleep aids (some of which are controlled substances), the potential drawback of abuse, addiction, and/or dependence necessitate recognition.
- Adverse reactions: Though extremely uncommon, a small percentage of individuals who administer gabapentin for sleep will experience severe adverse reactions. Various adverse reactions that can occur among gabapentin users include: allergic reactions (itching, hives, swelling, tingling, shortness of breath), fever, mood disturbances (e.g. major depression), nausea, skin rashes or skin blistering, and vomiting. Anyone who experiences an adverse reaction from gabapentin may regret utilizing the drug off-label to improve sleep.
- Cognitive deficits: It is known that a subset of individuals who take gabapentin will experience cognitive deficits and/or “brain fog” as side effects. Any cognitive deficits from gabapentin may impair academic and/or occupational performance, potentially jeopardizing the user’s future. Aspects of executive function may seem suboptimal while under the influence of gabapentin, such as: attention, cognitive flexibility, memory, planning, reasoning, self-regulation, etc. If your cognition is impaired from gabapentin, you may come to dislike the drug even if it effectively manages your sleep disturbances.
- Contraindications: No pharmaceutical medication is devoid of contraindications. If you have a medical condition with which gabapentin is contraindicated, this may be perceived as a drawback in that you may be unable to safely use the drug. Various contraindications associated with gabapentin include: hypersensitivity to gabapentin (or related compounds), neuropsychiatric disorders (e.g. major depression), and renal dysfunction.
- Coordination deficits: A side effect that many experience from sleep medications is impaired coordination upon waking [in the morning]. Certain individuals who administer gabapentin once nightly for sleep enhancement may also experience this side effect. Impaired coordination is a byproduct of CNS depression and is commonly accompanied by morning drowsiness and/or unclear thinking. What’s problematic is that many users won’t recognize that their coordination is impaired nor the potential consequences of this impairment such as increased risk of accidents (injury/death) while operating motor vehicles, heavy machinery, and or engaging in physical exercise.
- Ineffective: Though many have reported significant therapeutic benefit from the administration of gabapentin for the treatment of sleep disturbances, not everyone will find it effective. In fact, gabapentin may turn out to be relatively useless as a sleep aid for a subset of the populace due to factors such as: brain morphology, gene expression, and/or preexisting medical conditions. Those who find gabapentin to be ineffective for sleep may be disappointed with the fact that they gave it a test, especially if it also induced unwanted side effects.
- Inferiority: While there’s one study suggesting that gabapentin may be superior to trazodone for the treatment of alcohol dependence-related insomnia, it’s possible that gabapentin is an inferior intervention as compared to first-line hypnotics for the management of sleep disorders. We know that first-line hypnotics (e.g. zopiclone) have proven safe, tolerable, and effective in large-scale randomized controlled trials whereas gabapentin has not. Clearly the currently-available evidence supporting gabapentin as an intervention for sleep disorders is of markedly inferior quality compared to the evidence supporting FDA-approved first-line hypnotics. Moreover, even if gabapentin effectively mitigates sleep disturbances, a subset of individuals may find subjectively inferior to conventional hypnotics in terms of efficacy and/or tolerability.
- Interactions: Another drawback associated with gabapentin is that it may interact with other substances to provoke serious interaction-related effects such as fainting, respiratory depression, and/or death. Examples of substances that interact with gabapentin include: alcohol, barbiturates, benzodiazepines, hypnotics, opioids, and SSRIs. Due to potential interaction effects, users of certain substances (e.g. dietary supplements, pharmaceutical drugs, and/or illicit drugs) may be unable to safely administer gabapentin for the enhancement of sleep and/or treatment of sleep disturbances.
- Intoxication: As was mentioned, the abuse/misuse potential of gabapentin may be overlooked and/or underrated. Though impossible to gather perfect data regarding abuse/misuse, trends suggest that the recreational use of gabapentin has become increasingly popular in recent years. Many are administering high doses of gabapentin with the intent of experiencing relaxation and/or mood enhancement. Additionally, some individuals have reported intoxication despite taking gabapentin as directed by a medical professional. It’s possible that a subset of individuals who use gabapentin for sleep will experience intoxication. The intoxication may be unwanted [especially if it lingers upon waking] and/or so pleasurable that it leads to abuse, addiction, and/or dependence.
- Long-term effects: Research suggests that long-term users of gabapentin may experience dizziness, memory problems, and sedation. It is unclear as to whether these are general side effects sustained throughout treatment or long-term effects. Obviously it’s possible that they are long-term effects. Moreover, it’s possible that regular long-term administration of gabapentin modulates the user’s physiology to provoke adverse long-term effects – some of which could be permanent. A histological study by Olayemi, Olaibi, and Opeyemi (2014) indicates that a combination of carbamazepine plus gabapentin can lead to hippocampal degeneration in animals. While this study involved animals and a combination treatment (carbamazepine plus gabapentin), it’s possible that standalone gabapentin could accelerate and/or induce degeneration within structures of the human brain among long-term users.
- Low quality evidence: As of current, high-quality evidence supporting the efficacy of gabapentin for the treatment of sleep disorders is lacking. Although all preliminary data are consistent in suggesting that gabapentin effectively attenuates sleep disturbances, the quality of these data are low. For this reason, even if you find gabapentin to be effective as a sleep enhancer, it’ll probably be difficult to attain a prescription for this indication. Only after testing an array of evidence-based first-line and second-line hypnotics without benefit and/or tolerability might a medical professional consider prescribing gabapentin for sleep.
- Off-label: Because gabapentin is solely approved by the FDA for the treatment of postherpetic neuralgia and partial onset seizures (as an adjunct), its prescription for any other medical condition, including sleep disorders, would be considered off-label. Off-label medications like gabapentin are typically reserved for patients with refractory cases of sleep disturbances who don’t respond to first-line (FDA-approved) treatments. In other words, it will be more difficult to attain a gabapentin prescription specifically for the treatment of sleep disorders. Moreover, even if a gabapentin prescription is attained for sleep, it may be difficult to maintain this prescription if you ever end up with a new doctor (such as in the event of relocation); the new doctor may disagree with the previous doctor’s decision to prescribe gabapentin.
- Side effects: Even if gabapentin works well for the treatment of your sleep disorder, it may induce unwanted side effects. Common side effects reported among gabapentin users include: dizziness, somnolence, gait disturbance, and peripheral edema – respectively. Two of the most unwanted side effects that occur among gabapentin users are cognitive dysfunction and weight gain. (Read: “Does Gabapentin Cause Weight Gain?”). In the event that side effects become severe, they may significantly impair a person’s quality of life to the extent that gabapentin is deemed intolerable and/or warrants discontinuation.
- Tolerance onset: Long-term studies among patients who take gabapentin for the treatment of postherpetic neuralgia or partial onset seizures report that tolerance to gabapentin does not occur. In other words, patients who use the drug for FDA-approved conditions are thought to derive therapeutic benefit from a fixed-dose without any need for a dosage increase over a period of years. That said, commonsense and numerous anecdotal accounts suggest that tolerance is inevitable such that dosage increases are required. Although rate of tolerance onset may be slower among persons administering gabapentin once per night (q.h.s.) for sleep, eventually the efficacy of gabapentin may diminish. When tolerance occurs, a dosage increase will be needed to attain the same therapeutic effect, however, dosage increases can yield increasingly severe side effects. Eventually a person may develop tolerance to a maximal nightly dosage of gabapentin whereby sleep is no longer enhanced and side effects are intolerable.
- Unknown long-term efficacy: The long-term efficacy of gabapentin when administered specifically for the treatment of sleep disturbances remains unknown. It’s possible that gabapentin may prove efficacious over a span of months or years for the enhancement of sleep, yet eventually cease to facilitate a therapeutic effect. Most suspect that, even if administered once nightly for sleep, gabapentin users will develop tolerance to their current dose such that it’s no longer useful for sleep enhancement. While increasing the dosage may help temporarily, certain individuals may go on to develop tolerance to the maximum safe daily dosage. Moreover, in some cases, even if the dosage is increased to combat tolerance, the increase may not necessarily restore its therapeutic efficacy.
- Withdrawal symptoms: Though some may reap significant benefit from gabapentin for the treatment of sleep disorders, if the drug stops working and/or side effects become unbearable, discontinuation is usually warranted. Upon discontinuation, especially after a long-term of high-dose administration, many users report debilitating gabapentin withdrawal symptoms. Examples of these symptoms include: rebound sleep disturbances (e.g. frequent awakenings, insomnia, nightmares, etc.), anxiety, agitation, depression, dizziness, headaches, joint pain, nausea, cravings, and fatigue. The aforestated withdrawal symptoms may persist for weeks and/or months after discontinuation and significantly impair overall functionality and quality of life. Many claim that if they were properly informed of the withdrawal from gabapentin, they would’ve never used it – regardless of initial benefit.
Gabapentin’s Mechanism of Action for Sleep & Insomnia
Assuming you derive therapeutic hypnotic benefit from gabapentin, you may be curious to know the mechanism of action by which it modulates physiology to enhance sleep. Though the totality of its pharmacodynamic effect is unknown, researchers have successfully identified a host of neurobiological systems upon which gabapentin exerts an effect. The predominant mechanism by which gabapentin acts is through inhibition of alpha(2)delta (α2δ) subunits of voltage-gated calcium channels.
It is also understood that gabapentin modulates activation of glutamic acid decarboxylase (GAD) and branched-chain aminotransferase (BCAT) enzymes to increase synthesis of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter. Gabapentin also appears to modulate: NMDA receptors, protein kinase C, proinflammatory cytokines – and potentially GABA(B) receptors. Discussed below are specific mechanisms of gabapentin’s action in regards to how each may facilitate a therapeutic hypnotic effect to improve sleep.
Voltage-gated calcium (Ca+) channel inhibition: In the human brain, voltage-gated calcium channels modulate membrane depolarization-induced intraneuronal calcium (Ca+) influx. Pharmacodynamic investigations involving gabapentin indicate that it functions primarily by inhibiting α2δ subunits of voltage-gated calcium channels. Specifically, it appears as though gabapentin binds with highest affinity to α2δ-1 subunits and to a lesser extent, α2δ-2 subunits; there are no data indicating interactions with α2δ-3 and α2δ-4 subunits.
The aforestated α2δ subunits (α2δ-1 and α2δ-2) upon which gabapentin binds are associated with various types of voltage-gated calcium channels, including: N-type, L-type, P-type, and Q-type. (Though it has been hypothesized that gabapentin may interact with R-type voltage-gated calcium channels, further research is needed for verification). That said, each voltage-gated calcium channel influenced by gabapentin may play a role in the attenuation of sleep disturbances.
- N-type channels: N-type voltage-gated calcium channels regulate presynaptic neuron activation, neuronal signaling, and synaptogenesis. Gabapentin is a potent inhibitor of α2δ subunits on N-type channels. The inhibition of α2δ subunits of N-type channels is known to decrease both neuropathic and intractable pain. In the event that a person experiences insomnia and/or sleep disturbances from ongoing pain sensations, inhibiting activation of the N-type channel should attenuate the pain, which in turn should yield sleep improvement. Moreover, preliminary evidence suggests that N-type channel inhibition may prevent alcohol-induced intoxication. This considered, one might suspect that this is a mechanism by which gabapentin attenuates sleep abnormalities among persons with a history of alcohol dependence. There’s also evidence suggesting that N-type channel activity influences cholinergic transmission. Because cholinergic transmission is associated with wakefulness and rapid-eye-movement (REM) sleep, it’s possible that the N-type channel modulation alters choline to improve sleep.
- L-type channels: L-type voltage-gated calcium channels regulate cardiac and skeletal muscle excitation / contraction and aldosterone production within the adrenal cortex. In animals, gabapentin interacts with L-type channels to a lesser extent than N-type channels, but to a greater extent than other voltage-gated calcium channel types. Research indicates that inhibition of L-type channels may decrease blood pressure, induce muscle relaxation, and increase pain threshold. It’s reasonable to suspect that L-type channel inhibition could attenuate sleep disturbances through a myorelaxant and/or analgesic effect – each of which may be especially relevant among persons with anxiety and/or pain.
- P-type channels: P-type voltage-gated calcium channels regulate presynaptic neurotransmitter release analogous to N-type channels. Additionally, P-type channels modulate presynaptic release of neurohormone and vesicular activity. Research suggests that inhibition of P-type channels treats seizures and may modulate blood pressure, heart rate, and pain sensitivity. Among persons with sleep disturbances as a result of seizures, heart rate irregularities, and/or pain, the inhibition of P-type channels by gabapentin may prove therapeutic. Moreover, like N-type channels, P-type channels may influence cholinergic activity implicated in rapid-eye-movement (REM) sleep and wakefulness.
- Q-type channels: Q-type voltage-gated calcium channels are localized within cerebellar granule cells and have a high threshold for activation. Because Q-type channels are under-researched, it is unclear as to how their gabapentin-induced inhibition might prove therapeutic among persons experiencing sleep disturbances. Considering that cerebellar granule cell calcium influx affects things like membrane potential, synaptic plasticity, apoptosis, and gene transcription – it’s possible that inhibition of Q-type influences the aforestated processes in such a way as to enhance sleep.
- R-type channels: R-type voltage-gated calcium channels are present within a multitude of brain regions including the: amygdala, cortex, hippocampus, and striatum. Although it is unknown as to whether gabapentin interacts with R-type channels, some have hypothesized that it does. Inhibitors of R-type channels are known to facilitate anticonvulsant, antinociceptive, and mood stabilizing effects. Assuming that gabapentin inhibits R-type channels, this may attenuate sleep disturbances resulting from seizures, pain sensations, and/or mood swings.
When considering that a subset of individuals likely experience sleep disturbances as a direct result of voltage-gated calcium channel dysregulation, it’s logical to suspect that modulation of dysregulated channels by gabapentin could ameliorate the preexisting dysregulation to improve sleep. Even among persons without preexisting voltage-gated calcium channel dysregulation [as an underlying cause of sleep disturbances], it’s known that modulation of voltage-gated calcium channels can treat specific symptoms of medical conditions implicated in disturbed sleep. Examples of such symptoms might include: neuralgia, seizures, neuropathic pain, intractable pain, anxiety, restlessness, headache, and mood swings.
Furthermore, in addition to ameliorating dysregulated voltage-gated calcium channels and/or treating specific symptoms of medical conditions implicated in disturbed sleep, it’s likely that gabapentin-mediated voltage-gated calcium channel modulation alters physiology in ways that are conducive to sleep such as by decreasing excitatory neurotransmission, downregulating sympathetic tone, and modifying neuroelectrical activity (brain waves). This helps explain why individuals devoid of preexisting neurochemical imbalances and/or medical conditions report sleep enhancement from gabapentin. In sum, because inhibition of voltage-gated calcium channels is the chief mechanism of gabapentin’s action, it’s fair to suspect that this is the most relevant mechanism by which the drug enhances sleep.
GABA synthesis: Gabapentin was originally engineered as a synthetic analogue of the neurotransmitter GABA (gamma-aminobutyric acid) and thought to exert similar effects within the CNS as endogenous GABA. While the primary mode of gabapentin’s action is not GABAergic, neuroimaging research supports the idea that it increases GABA synthesis via interactions with glutamic acid decarboxylase (GAD) and branched-chain aminotransferase (BCAT) enzymes. Because GABA is the predominant inhibitory transmitter within the CNS, increasing its production likely enhances GABAergic signaling to offset insomnia and/or sleep disturbances caused by excessive excitatory transmission.
Glutamic acid decarboxylase (GAD): The enzyme glutamic acid decarboxylase is responsible for catalyzing the decarboxylation of glutamate to GABA [and CO2]. Gabapentin appears to upregulate activation of the glutamic acid decarboxylase enzyme, which in turn, increases production of GABA. Researchers Fitzgerald and Carter (2011) have outlined many correlations between glutamic acid decarboxylase activity and symptoms of medical conditions associated with sleep disruption. For example, reduced glutamic acid decarboxylase activity is reportedly associated with: fibromyalgia, increased pain sensitivity, muscle tension, anxiety, and depression – each of which can interfere with sleep. What’s more, decreased glutamic decarboxylase activity is directly linked with abnormal NREM (non-rapid eye movement) and corresponding poor sleep. For some individuals, gabapentin-induced glutamic acid decarboxylase activation may attenuate medical symptoms that were disturbing sleep. Additionally, increasing glutamic acid decarboxylase activation may also enhance sleep quality via normalization of NREM.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/21684692
- Source: https://www.ncbi.nlm.nih.gov/pubmed/10515993
Branched-chain aminotransferase (BCAT): There are multiple formats of the enzyme branched-chain aminotransferase within the brain, namely: BCATm (peripheral and associated with mitochondria) and BCATc (cystolic and associated with cerebral tissue). Research indicates that gabapentin competitively inhibits BCATc due to the fact that it’s structurally similar to leucine. The competitive inhibition of BCATc by gabapentin is thought to inhibit glutamate secretion while simultaneously enhancing GABA secretion. Although no research has investigated the relationship between branched-chain aminotransferase activation and sleep, it’s possible that modulation of BCAT via gabapentin yields sleep enhancement.
Although gabapentin may increase GABA via interactions with both glutamic acid decarboxylase (GAD) and branched-chain aminotransferase (BCAT), it remains unclear as to whether more significant GABA increases are attained from interaction with one enzyme or the other. It’s necessary to consider that gabapentin-induced activation of each enzyme might be weighted in terms of GABA production and/or therapeutic benefit (e.g. 75% from GAD, 25% from BCAT) or relatively equal. However, based on evidence suggesting that glutamic acid decarboxylase activation influences sleep quality, it’s reasonable to suspect that interaction with glutamic acid decarboxylase yields greater sleep enhancement than interaction with branched-chain aminotransferase.
In any regard, it is known that deficits in GABAergic signaling can directly cause insomnia and/or sleep disturbances as well as many medical symptoms that interfere with sleep such as agitation, anger, anxiety, and restlessness. For example, a study by Winkelman, Orfeu, Buxton, et al. (2008) discovered that average brain concentrations of GABA were approximately 30% lower in persons with primary insomnia compared to persons without insomnia. Other research has linked deficits in GABAergic signaling to HPA axis hyperactivity and CNS hyperarousal.
Predictably, evidence suggests that increasing GABAergic signaling can improve sleep and/or treat sleep disorders. Additionally, most first-line hypnotics act through modulation of the GABA system, particularly by activating the GABA(A) receptor. Because gabapentin upregulates GABA production through interactions with glutamic acid decarboxylase and branched-chain aminotransferase, most would suspect that this yields greater activation of GABA receptors and suppresses CNS activity.
For certain persons, this CNS suppression may reverse deficient inhibitory transmission and/or attenuate excessive excitatory transmission – each of which could be causally implicated in a sleep disorder. Furthermore, the upregulation of GABAergic signaling may be enough to induce a combination of anxiolytic, hypnotic, and myorelaxant effects whereby it becomes easier to fall asleep and/or maintain deeper sleep – especially if GABA(A) receptors are activated – regardless of homeostatic neurochemistry. That said, the extent to which gabapentin-mediated GABAergic signaling is relevant as a mechanism of hypnotic action may be contingent upon dosing and/or duration of administration.
Research by Kejia, Cai, Ravi, et al. (2012) indicates a single dose of gabapentin at 900 mg increases cortical GABA by approximately 5.6%, whereas ongoing administration of gabapentin at 900 mg increases cortical GABA by approximately 55%. This suggests that ongoing administration increases likelihood of a GABAergic mechanism playing a significant role in the management of sleep disorders. Moreover, even if increased GABA signaling isn’t therapeutic as a standalone mechanism of hypnotic action, it may complement voltage-gated calcium channel blockade, gabapentin’s primary mode of action, in the generation of a hypnotic effect.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/19014069
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499716/
Other mechanisms of Gabapentin that may enhance sleep
In addition to gabapentin’s primary action as an inhibitor of voltage-gated calcium channels and [hypothesized] secondary action as an upregulator of GABA production, it also interacts with: NMDA receptors, monoaminergic transmission, nitric oxide synthase, and inflammatory cytokines. It is unclear as to whether these interactions are downstream signaling byproducts of its primary action or whether these interactions are distinct. Nonetheless, while these actions may be of marginal physiologic magnitude, they warrant mentions insofar as they may contribute to gabapentin’s hypnotic effect.
- Cytokine regulation: It is known that, for a subset of persons, proinflammatory cytokines are causally implicated in sleep disturbances. What’s more, preexisting sleep disturbances can increase proinflammatory cytokines, which in turn, can deleteriously modulate neurochemistry and exacerbate and/or inhibit recovery from sleep disturbances. There’s some evidence from animal studies suggesting that gabapentin administration increases expression of anti-inflammatory cytokines such as interleukin-10 and decreases expression of proinflammatory cytokines such as interleukin-1B and TNF-alpha. If gabapentin favorably regulates cytokine expression in humans, it’s reasonable to suspect that this would ameliorate the severity of sleep disturbances.
- Monoamine modulation: Gabapentin appears to modulate concentrations of monoamines throughout the brain. Specifically, gabapentin is thought to: slightly increase norepinephrine secretion in the locus coeruleus and spinal cord; inhibit dopamine secretion in the caudate nucleus; and upregulate peripheral serotonin concentrations without affecting melatonin. There’s also research indicating that gabapentin reduces total catecholamine (norepinephrine, epinephrine, dopamine) secretion implicated in the stress response. Any reduction in catecholamine signaling during the stress response may prevent stress-induced sleep disturbances. Moreover, the modulation of norepinephrine by gabapentin [in particular] is thought to reduce certain types of pain (e.g. neuropathic), which may yield sleep improvement among persons with pain-related sleep disturbances. Finally, because monoamine signaling influences arousal and mood, any sleep disturbances attributable to hyperarousal and/or preexisting mood disorders may improve directly from gabapentin-mediated monoaminergic modulation.
- Nitric oxide synthase (NOS): In-vivo research suggests that gabapentin increases neuronal nitric oxide synthase (nNOS) in central and peripheral locations. Neuronal nitric oxide synthase is an enzyme involved in the generation of nitric oxide by neurons plus neuronal communication. The increase in nitric oxide synthase may be conducive to sleep. Evidence to support the idea that nitric oxide synthase influences sleep comes from research by Kalinchuk, Stenberg, Rosenberg, and Porkka-Heiskanen (2006). The aforementioned researchers discovered that, in animal models, the inhibition of nitric oxide synthase prevents NREM sleep and recovery sleep after prolonged wakefulness. Though the significance of gabapentin’s effect on neuronal nitric oxide synthase (nNOS) is unclear, it’s possible that increasing neuronal nitric oxide synthase facilitates promotes NREM sleep and bolsters recovery sleep after an extended duration of disturbed sleep. (Source: https://www.ncbi.nlm.nih.gov/pubmed/16987226).
- NMDA receptor inhibition: There’s evidence suggesting that gabapentin non-competitively inhibits NMDA receptors in a concentration-dependent manner. Because NMDA receptor inhibition is associated with the generation of an antinociceptive effect, it’s reasonable to assume that this mechanism of gabapentin’s action could attenuate pain among persons with chronic pain conditions, thereby aiding in mitigation of pain-related sleep disturbances. What’s more, research suggests that degree of NMDA receptor activation [in certain regions of the brain] influences sleep/wakefulness. In fact, some studies have discovered that NMDA receptor agonists can increase gamma brain waves and wakefulness, whereas NMDA receptor antagonists can increase delta brain waves and NREM sleep. Perhaps gabapentin-mediated inhibition of NMDA receptors plays a more significant role in the enhancement of sleep than many suspect.
- Sodium (Na+) channel inhibitor: There’s some data from electrophysiological assays suggesting that gabapentin modestly inhibits voltage-gated sodium channels (Nav1.7) within the dorsal root ganglion (DRG) of animals. Assuming the gabapentin-mediated inhibition of voltage-gated sodium channels in the dorsal root ganglion also occurs in humans, there’s reason to suspect that this would augment the hypnotic effect of other gabapentin mechanisms (e.g. voltage-gated calcium channel inhibition, upregulation of GABA, etc.). Augmentation of a preexisting hypnotic effect via voltage-gated sodium channel inhibition [in the dorsal root ganglion] may occur from a reduction in excitatory transmission, perhaps most notably of orexin, a wakefulness transmitter that can cause insomnia and sleep disturbances. Moreover, the blockade of sodium channels has been shown to facilitate an analgesic effect, which may prove useful in mitigating pain-related sleep disturbances. Overall, even modest inhibition of sodium channels by gabapentin may play a complementary mechanistic role in the normalization or enhancement of sleep.
- Substance P reduction: Gabapentin has been shown to inhibit release of substance P, a neuropeptide that influences anxiety, inflammation, mood, and pain. The secretion of substance P is associated with increased anxiety, neurogenic inflammation, depressed mood, and amplification of physical pain. Research by Lieb, Ahlvers, Dancker, et al. (2002) indicates that elevated substance P deleteriously affects sleep. Specifically, substance P infusions increase wakefulness, REM latency, and Stage 1 sleep. Knowing that gabapentin may reduce substance P, it’s rational to suspect that this mechanism would enhance sleep. A study by Field, Diego, Cullen, et al. (2002) supports the idea that lower substance P is associated with increased sleep duration and fewer sleep movements. (Source: https://www.ncbi.nlm.nih.gov/pubmed/12464461, Source: https://www.ncbi.nlm.nih.gov/pubmed/17041326).
The exact degree to which each of the aforestated [hypothesized] mechanisms of gabapentin’s action facilitate a therapeutically-relevant hypnotic effect is unknown. It’s possible that a specific mechanism or a combination of mechanisms are responsible for facilitating the totality of gabapentin’s hypnotic effect. For example, maybe voltage-gated calcium channel inhibition may be the only relevant hypnotic mechanism.
Another possibility is that multiple mechanisms contribute in varying amounts to the generation of a hypnotic effect. For example, voltage-gated calcium channel inhibition may account for 70% of the hypnotic effect, increased GABA synthesis for 15% of the effect, NMDA receptor inhibition for 10% of the effect, and cytokine modulation for 5% of the effect. Moreover, it must be considered that the hypnotic efficacy of each mechanism may be subject to individual variation.
In other words, a person with sleep disturbances stemming from deficits in cortical GABA may benefit most from enhancement of GABA synthesis, whereas someone with overactive NMDA receptors may benefit more from the NMDA receptor inhibition. These individual differences may be related to brain morphology, genetic expression, medication and/or supplement regimen, and lifestyle.
Gabapentin for Sleep & Insomnia: Review of Research
To determine whether gabapentin is efficacious for the enhancement of sleep and/or treatment of insomnia, it is necessary to examine results from relevant studies [in which gabapentin was formally assessed as a sleep aid]. Included below is compilation of all relevant studies along with a brief summary of each. As of current, results from all available studies are consistent in suggesting that gabapentin is likely useful as a sleep enhancer and/or insomnia attenuator – across a variety of populations.
2016: The Effect of a Novel form of Extended-Release Gabapentin on Pain and Sleep in Fibromyalgia Subjects: An Open-Label Pilot Study.
In 2016, results from an open-label pilot study conducted by North, Hong, and Rauck were published in which extended-release gabapentin was administered to individuals with fibromyalgia. The primary aim of the study was to determine whether gabapentin could alleviate pain, but a secondary aim was to determine whether gabapentin could enhance sleep. For the study, researchers assigned 34 fibromyalgia-diagnosed individuals to receive gabapentin ER (extended-release) starter packs for a duration of 12 weeks.
Prior to commencement of the study, all participants were evaluated with the following tests: Numeric Pain Rating System (NPRS), Fibromyalgia Impact Questionnaire (FIQ), Patient’s Global Impression of Change (PGIC), and Medical Outcome Sleep (MOS) survey. At 4-week intervals, participants were reevaluated with the same tests and changes were documented. Of the 34 enrolled participants, 29 managed to complete their gabapentin ER starter packs.
Results indicated that patients experienced significant pain relief within 4 weeks as evidenced by reductions in NPRS scores. What’s more, the MOS survey indicated that participants exhibited increases in average sleep duration per night (~1.2 hours) and significantly enhanced sleep quality. Overall, the results of this study highlight the fact that gabapentin ER can alleviate symptoms of fibromyalgia-related pain plus improve sleep quantity and quality.
Researchers involved in the trial acknowledged various potential limitations including: small sample, geographical bias, short-term treatment, and lack of randomization/controlling. Furthermore, because gabapentin appeared to significantly reduce fibromyalgia-related pain, it’s possible that the reported sleep enhancement was a byproduct of pain reduction rather than the pharmacodynamics of gabapentin. After all, most would suspect that it would be easier to fall asleep and stay asleep with effective treatment of preexisting pain.
Because this study solely recruited persons with fibromyalgia, it’s possible that the reported sleep enhancing effect would not occur among those without fibromyalgia. All that said, the findings of the study support the idea that an extended-release (ER) format of gabapentin could significantly enhance sleep by increasing sleep time (to reverse a deficit) and by improving subjective sleep quality.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/26059271
2015: Comparing Gabapentin with Clonazepam for Residual Sleeping Problems following Antidepressant Therapy in Patients with Major Depressive Disorder: A Randomized Clinical Trial.
Mowla, Ahmadzadeh, Razeghian Jahromi, and Dastgheib (2015) discussed the fact that a subset of patients who receive treatment for major depression experience residual sleep disturbances. The researchers suggest that residual sleep disturbances among these patients may induce functional impairments, increase risk of depressive relapse, and/or lead to the development of treatment-resistant depression. For this reason, they organized a double-blind, randomized controlled trial (RCT) in which the drugs gabapentin and clonazepam were evaluated for the treatment of residual sleep disturbances.
A total of 63 individuals that met DSM-IV diagnostic criteria for major depression were recruited for participation. It was noted that all participants had received treatment with selective-serotonin reuptake inhibitors (SSRIs). After treatment with the SSRIs, patients’ depressive symptoms were significantly reduced [as evidenced by significant reductions in Hamilton Depression Rating Scale (HDRS) scores], however, sleep disturbances were apparent [as evidenced by scores on the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)].
Patients were assigned at random to receive either gabapentin (100-600 mg/day) OR clonazepam (0.5-2 mg/day) as an adjunct to their SSRI – for a 4-week duration. The efficacy of gabapentin and clonazepam for the treatment of lingering sleep disturbances was determined based on change in PSQI, ISI, and CGI scores from baseline to endpoint. Results of the study indicated that sleep disturbances had significantly decreased among recipients of gabapentin and clonazepam by the end of the trial [as evidenced by changes in PSQI and ISI scores].
Neither drug appeared more effective or tolerable than the other. It was concluded that gabapentin and clonazepam appear efficacious for the treatment of residual sleep disturbances among persons treated for major depression. Overall, this provides evidence to support the idea that gabapentin is a useful sleep aid.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/26123629
2013: Administration of four different doses of gabapentin reduces awakening from breakthrough pain and adverse effects in outpatients with neuropathic pain during the initial titration.
A randomized 24-month study conducted by Yang, Lee, Shin, et al. (2013) sought to determine the most therapeutically-effective titration regimen of gabapentin for the treatment of neuropathic pain and pain-related sleep disturbances. All participants in the study were outpatients that had been formally diagnosed with neuropathic pain, as well as exhibited at least 2 additional nonspecific symptoms such as: allodynia, burning pain, hyperalgesia, or shooting pain. In the study, researchers assigned participants to receive gabapentin either: three times per day (t.i.d.) in equal doses OR four times per day (q.i.d.) in divided doses – during an initial titration phase.
To gauge the efficacy and tolerability of each gabapentin dosing regimen during an initial titration, researchers recorded participants’ daily pain scores, breakthrough pain frequency, pain severity, pain duration, sleep disturbances, and adverse reactions to the drug. Results indicated that recipients of gabapentin four times per day (q.i.d.) in divided doses exhibited the greatest reductions in daily pain scores and pain-related sleep disturbances plus the fewest side effects during an initial titration phase – as compared to recipients of gabapentin three times per day (t.i.d.).
That said, there were no differences in breakthrough pain frequency, pain severity, and pain duration based on the titration regimen. Considering the results, researchers concluded that administration of gabapentin four times per day during an initial titration phase among persons with neuropathic pain yields the most significant reduction in pain-related sleep disturbances and minimizes gabapentin side effects. From a macro-perspective, this study provides further support for the idea that the administration of gabapentin improves sleep.
In this particular study most would suspect that the sleep improvement derived from gabapentin was principally attributable to its treatment of neuropathic pain such that, when the pain is sufficiently treated, participants’ sleep improves. Nevertheless, it’s possible that, in addition to treating neuropathic pain for improved sleep, gabapentin induces an effect upon physiology that enhances sleep irrespective of the neuropathic pain reduction. In other words, not only might sleep improve because neuropathic pain is reduced, but it might improve because gabapentin is modulating other aspects of physiology that are conducive to enhancement of sleep.
Moreover, while this study focused specifically on responses to gabapentin during an initial titration, we could hypothesize that the administration frequency during maintenance dosing also matters. For example, the administration of gabapentin four times per day (q.i.d.) during maintenance dosing may be more efficacious for the treatment of sleep disturbances than the administration of gabapentin three times per day (t.i.d.). Additionally, it may be worth comparing the efficacy and tolerability of several dosing intervals (e.g. b.i.d.; t.i.d.; q.i.d.) and/or equal vs. unequal dosing regimens. Lastly, while the findings of this study may only be relevant to persons with neuropathic pain, we should not discount the possibility that all gabapentin users may derive greater sleep enhancement from four-times-per-day (q.i.d.) dosing during an initial titration than from three-times-per day (t.i.d.).
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726847/
2012: Nighttime awakenings responding to gabapentin therapy in late premenopausal women: a case series.
As of 2012, a series of case reports were documented and published by Thomas Guttuso (M.D.) in which several women successfully treated sleep disturbances with gabapentin. In all 3 of the cases, women had been experiencing unwanted recurrent nighttime awakenings over a span of years. The recurrent nighttime awakenings were interfering with sleep quality and quantity, which induced symptoms associated with sleep deprivation such as: cognitive deficits, fatigue, excessive daytime sleepiness, and irritability.
It would eventually be discovered that each of the women experienced recurrent nighttime awakenings as a result of premenopausal-related hormone fluctuations. In menopause, frequent nighttime awakenings are thought to occur due to fluctuations in serum hormones such as decreased estradiol and increased adrenocorticotropic hormone (ACTH). While asleep, the aforestated hormonal fluctuations stimulate the sympathetic nervous system to provoke hot flashes, night sweats, and disconcerting nighttime awakenings. Interestingly, gabapentin appeared highly efficacious for the treatment of menopause-related hormone fluctuation-induced sleep disturbances.
Case #1: The first case discussed by Guttuso involved a 48-year-old woman who had reported frequent nighttime awakenings spanning over a 3-year duration. She described the awakenings as akin to being “shocked awake” from a deep sleep and noted that they occurred an average of 2 to 3 times per night, at least 3 nights per week. Because of these regular awakenings that disturbed her sleep, the woman experienced cognitive impairment, excessive daytime sleepiness, and emotional instability.
In attempt to treat these nighttime awakenings, a medical professional prescribed trazodone, and subsequently, amitriptyline – neither of which reduced the awakenings. The woman would eventually report that, after some of her awakenings, she felt hot and sweaty. The hot flashes and sweats led her doctor to suspect that menopause-related hormone imbalances may have been culpable for her ongoing sleep disturbances.
Although her follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were within normative ranges, her doctor recommended that she increase the dosage of her oral contraception. For a 2-month duration, she administered the increased dose of oral contraception with no improvement in sleep. Because the woman was disinterested in hormone replacement therapies, her doctor opted to prescribe gabapentin at a dosage of 300 mg at bedtime [with the thought that gabapentin may mitigate hot flashes and night sweats to prevent awakenings].
Initially, the patient derived significant benefit from 300 mg of gabapentin administered once per night such that she was able to get a full night’s sleep without awakenings or sweats. However, after a 2-week duration, the awakenings reemerged along with the sweats. Due to the reemergence of awakenings, the doctor increased her gabapentin dosage to 600 mg per night, and at this dosage, her nighttime awakenings and sweats subsided.
Although the woman experienced some morning dizziness as a side effect of gabapentin, it was manageable. Whenever the woman attempted to discontinue gabapentin, she experienced a relapse of awakenings and night sweats. Further FSH and LH testing would confirm that the woman had been premenopausal, indicating that nighttime awakenings were likely associated with drops in estradiol concentrations. This first case clearly supports the efficacy of gabapentin administered nightly (q.h.s.) for the treatment of menopause-related awakenings.
Case #2: The second case documented by Guttuso involved a 42-year-old woman with a history of nighttime awakenings that disturbed her sleep for over 2 years. In this case, the nighttime awakenings were reported to have occurred between 2 and 5 times per night, every night, and at relatively predictable times. Not only did the nighttime awakenings impair the woman’s sleep quality, but they caused excessive daytime sleepiness and irritability.
Upon seeking medical help for her nighttime awakenings, the patient denied experiencing hot flashes or night sweats – each of which would’ve indicated that hormonal fluctuations may be the cause. That said, of interest to her doctor was the fact that nighttime awakenings were more frequent and severe within 2 days prior to her menses, as well as throughout the first 5 days of her menses each month. After accounting for the patient’s age and symptomatic aggravation circa the onset of her monthly menses, low serum estradiol was suspected as causally implicated in the sleep disturbances.
Based on the similar symptoms to the woman discussed in “Case #1” and her favorable response to gabapentin, this woman also received a prescription for gabapentin for the management of her sleep disturbances. Within 2 days of gabapentin commencement at the 300 mg dose, the nighttime awakenings significantly decreased. However, like the woman in Case #1, this patient experienced a relapse of nighttime awakenings within several weeks of gabapentin initiation.
For this reason, her gabapentin dosage was increased to 600 mg per night. Although the nightly dose of 600 mg controlled nighttime awakenings for an additional 6-week period, its efficacy diminished, requiring a further dosage increase to 900 mg per night. The patient derived sustained therapeutic benefit from the 900 mg nightly dose and stabilized, noticing improvements in daytime alertness and mood. This is yet another case in which gabapentin was shown to effectively treat a sleep disturbance.
Case #3: The third case highlighted by Guttuso involved a 46-year-old woman with a 6-year history of nighttime awakenings with predictable corresponding symptoms such as poor concentration, daytimes sleepiness, and fatigue. In fact, the combination of poor concentration, daytime sleepiness, and fatigue became so severe – that the woman needed caffeine throughout the day just to maintain wakefulness and productivity at work. Upon seeking professional medical help, it was reported that the woman’s awakenings occurred at the same approximate time each night (~2:30 AM) and left her struggling to fall back asleep.
Neither hot flashes nor sweats had initially occurred during the nighttime awakenings, however, as the nighttime awakenings became increasingly severe, the woman noticed mild hot flashes. The occurrence of hot flashes led her doctor to suspect that the awakenings may be hormone related – particularly attributable to low serum estradiol. Because gabapentin is thought to prevent hot flashes and enhance sleep, the woman received a prescription for gabapentin to be administered at 300 mg per night for 3 nights, followed by 600 mg per night thereafter.
Within 4 days of gabapentin treatment, nighttime awakenings completely abated, and within 2 weeks of gabapentin treatment, the patient exhibited improvements in daytime concentration, vigilance, and energy. Favorably, the patient reported zero unwanted side effects from gabapentin. Like the first 2 cases, this third case provides additional evidence to support the usefulness of gabapentin for the treatment of sleep disturbances.
Everything considered, the series of case reports presented by Thomas Guttuso indicate that gabapentin may be an effective intervention for the treatment of nighttime awakenings among premenopausal and menopausal women. It seems as though nightly administration of either 600 mg or 900 mg effectively attenuates premenopausal nighttime awakenings plus associated symptoms such as hot flashes and night sweats – with few side effects. That said, because this is merely a series of 3 case reports [and not a large-scale randomized controlled trial], it’s possible that the therapeutic benefit derived from gabapentin is explained by a placebo effect.
Moreover, it’s worth noting that Thomas Guttuso (the author of this report) is listed as the inventor on a patent associated with the usage of gabapentin for the treatment of hot flashes and night sweats – highlighting a potential conflict of interest. If approved for the treatment of hot flashes by the FDA, Thomas Guttuso would receive financial compensation for its sales. Regardless of potential conflicts of interest, these cases showcase the therapeutic potential of using gabapentin for sleep.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/22505864
2011: Adjunctive gabapentin for treatment-resistant insomnia of bipolar disorder: a case report.
Egashira, Inoue, Shirai, et al. (2011) documented a case report in which adjunct gabapentin effectively treated refractory insomnia in a patient with bipolar disorder (type 2). Medical professionals noted that this particular patient exhibited a combination of severe symptoms including: mixed depression, mood fluctuations, impulsivity (as evidenced by buying sprees), impaired cognition, and refractory insomnia. In fact, the aforestated symptoms were so debilitating, that the patient was unable to work.
Transitioning the patient to a combination of carbamazepine and risperidone led to mood stabilization and impulsivity reduction, however, unwanted insomnia-related symptoms still lingered such as: nighttime awakenings and sleep-related anxiety. The patient underwent trials with adjunctive benzodiazepines, followed by antipsychotics – neither of which effectively treated the patient’s insomnia. Next, gabapentin was prescribed as an adjunct to carbamazepine and risperidone with the intent of attenuating insomnia-related symptoms.
Not only did the gabapentin attenuate the patient’s refractory insomnia, it facilitated additional mood enhancement. Furthermore, after stabilizing on the combination of carbamazepine, risperidone, and gabapentin, symptoms were adequately controlled such that the patient was able to reinstate work. The results of this case report suggest that adjunctive gabapentin can treat refractory insomnia among patients with bipolar disorder.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/21586919
2010: Treatment effects of gabapentin for primary insomnia.
Lo, Yang, Lo, et al. (2010) noted that while there are plenty of effective pharmacological interventions for insomnia, many first-line hypnotics deleteriously modify sleep architecture and provoke adverse reactions. An alternative pharmacological intervention to first-line hypnotics is gabapentin, an agent that has been shown to enhance slow-wave sleep in healthy persons with few side effects. Because gabapentin may be as effective as first-line hypnotics, but superior in terms of its modulation of sleep architecture and tolerability, researchers sought to test its therapeutic potential among patients diagnosed with primary insomnia.
A study was organized in which 18 patients diagnosed with primary insomnia were assigned to receive gabapentin for a minimal duration of 4 weeks. Prior to receiving gabapentin (baseline) and after receiving gabapentin (endpoint), patients underwent various assessments including: polysomnography, biochemical blood tests, and neuropsychological tests. Polysomnography readings revealed: increased in sleep efficiency and slow-wave sleep; reduced wake after sleep onset; and lower spontaneous arousal index – after gabapentin treatment.
Biochemical blood assays showed reductions in concentrations of prolactin in the morning after gabapentin administration. Electroencephalography (EEG) readings indicated that gabapentin altered brain waves during sleep, particularly by increasing delta-2 and theta amplitude in Stage 1 of sleep and by reducing sigma activity in Stages N2 and N3 of sleep. Moreover, gabapentin appeared to increase heart rate-variability (HRV) during Stages N2 and N3 of sleep – plus increased visual motor processing speed in neuropsychological tests.
Researchers concluded that the administration of gabapentin increases slow-wave sleep and sleep efficiency while decreases spontaneous arousal. Although this study was relatively small-scale (with just 18 participants) and short-term, its findings support the hypothesis that gabapentin can effectively treat primary insomnia while favorably modulating sleep architecture. That said, a larger randomized controlled trial is needed to rule out placebo responses and strengthen the quality of data.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/20124884
2009: Effects of gabapentin on sleep in menopausal women with hot flashes as measured by a Pittsburgh Sleep Quality Index factor scoring model.
It is known that menopausal women are prone to sleep disturbances as a result of hormone fluctuations such as low serum estradiol. Hormone fluctuations tend to trigger a sympathetic response to induce sleep disturbances such as insomnia and/or frequent awakenings throughout the night – each of which are often accompanied by hot flashes. A potentially-useful intervention for the treatment menopause-related sleep disturbances is gabapentin, an agent that appears helpful in the management of menopause-related hot flashes.
To determine whether gabapentin might enhance sleep among menopausal women, researchers Yurcheshen, Guttuso, McDermott, et al. (2009) conducted a secondary analysis of data from a double-blind, randomized, placebo-controlled trial involving menopausal women. In the trial, menopausal women were assigned to receive either: a placebo OR gabapentin three times per day (t.i.d.) in equal doses of 300 mg per dose – for a 12-week duration.
The efficacy of gabapentin for the treatment of sleep disturbances determined based upon changes in Pittsburgh Sleep Quality Index (PSQI) scores from pre-treatment (baseline) through the endpoint. Results indicated that the recipients of gabapentin exhibited significant improvements in: sleep quality factor scores, global PSQI scores, and sleep efficiency throughout the trial – as compared to recipients of the placebo. That said, the daily disturbance factor scores did not differ between the placebo and gabapentin recipients.
It was concluded that gabapentin might enhance sleep quality in menopausal women with hot flashes. Based on the fact that a host of significant improvements were observed in measures of sleep quality, sleep efficiency, and global sleep scores – this study supports the idea that gabapentin can enhance sleep.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/19708803
2005: Gabapentin improves sleep in the presence of alcohol.
Bazil, Battista, and Basner (2005) conducted a trial to assess whether a standalone dose of gabapentin could ameliorate sleep disturbances associated with alcohol intake. The trial implemented a double-blind, randomized, single-dose, crossover design and recruited 13 participants between the ages of 21 and 45. It was noted that all participants were devoid of preexisting sleep disorders and medical conditions that could negatively affect sleep.
To establish a baseline, all participants entered a sleep lab for one night, underwent a polysomnographic assessment, and completed subjective scales of drowsiness and function upon waking. Approximately 1 to 2 weeks later, participants reentered the sleep lab for one night and consumed 4 ounces of 40% alcohol 1-hour before bedtime. Along with the alcohol, participants received either: gabapentin (300 mg or 600 mg) OR a placebo.
Similar to baseline, participants underwent a polysomnographic assessment and completed subjective scales of drowsiness and functioning upon waking. Between 1 and 2 weeks later, participants reentered the sleep lab and received either: gabapentin (if they received the placebo initially) or the placebo (if they received gabapentin initially) – along with the same 4 ounces of 40% alcohol 1-hour before bedtime. Polysomnographic assessments and subjective scales of drowsiness and functioning were completed.
Of the 13 enrolled participants, 12 were able to complete the study. Results indicated that there were no differences in total sleep time based on whether a person received gabapentin versus the placebo. That said, gabapentin administration was associated with significant reductions in Stage 1 sleep, fewer awakenings, and increased sleep efficiency.
Moreover, recipients of the 600 mg dose exhibited enhanced slow-wave sleep (SWS), less rapid-eye movement (REM) sleep, and fewer arousals. Although the polysomnographic assessments clearly indicated improved sleep following gabapentin administration, no differences were discovered on subjective scales of drowsiness and functioning. Nonetheless, researchers concluded that single-dose gabapentin appears to enhance many aspects of sleep [after alcohol consumption].
Researchers also suggested that gabapentin may effectively treat sleep disturbances associated with frequent awakenings and/or poor sleep efficiency. However, because this study is limited by its small sample size, a larger-scale follow-up trial may be warranted to solidify findings. In any regard, this is yet another trial in which gabapentin improves sleep.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/17566190
2003: Open pilot study of gabapentin versus trazodone to treat insomnia in alcoholic outpatients.
Karam-Hage and Brower (2003) sought to compare the effectiveness of gabapentin versus trazodone for the management of alcohol-related insomnia. The researchers organized a trial in which 55 outpatients diagnosed with alcohol dependence [in accordance with DSM-IV criteria] were assigned to receive either: gabapentin OR trazodone – for the treatment of unremitting insomnia. It was noted that the unremitting insomnia was not attributable to substance intoxication nor alcohol withdrawal, and mentioned that all participants had remained abstinent from alcohol for a minimum of 4 weeks prior to the study – as was confirmed by breath tests and urinalyses.
Gabapentin was initiated at a dosage of 300 mg nightly and titrated upwards “as-needed” to a maximum dosage of 1800 mg nightly. Trazodone was initiated at 25 mg nightly and titrated upwards “as-needed” to a maximum dosage of 300 mg nightly. All patients received instruction to administer their medication 30 to 60 minutes before bed.
To assess the efficacy of gabapentin and trazodone, patients completed the Sleep Problems Questionnaire (SPQ) at baseline and after 4 to 6 weeks of treatment. By the trial endpoint, 3 (8%) of the 37 gabapentin users and 2 (11%) of 18 trazodone users discontinued after the first dose due to unwanted side effects. Results indicated that SPQ scores of trazodone and gabapentin users did not differ at baseline, and that users of each drug exhibited significant SPQ score improvements at follow-up versus baseline.
That said, total change of SPQ scores from baseline to follow-up was more significant among gabapentin users compared to trazodone users. The greater SPQ score improvements among gabapentin users remained even after controlling for confounds such as: age, baseline SPQ scores, and sex. Researchers discussed the fact that both gabapentin and trazodone effectively treated insomnia among alcohol-dependent patients who refrained from alcohol usage for at least 4 weeks.
Nonetheless, it was mentioned that gabapentin users exhibited greater symptomatic improvement when compared directly with trazodone users. Specifically, gabapentin users experienced less initial insomnia and were less likely to report “feeling tired and worn out” upon waking. Neither agent was regarded as more tolerable than the other – as evidenced by similar dropout rates.
Various limitations associated with the trial were acknowledged by researchers including: lack of randomization, lack of a placebo control, lack of blinding, the small sample size, short-term trial duration, failure to collect polysomnography readings, and possible inequalities in medication dosing [with respect to hypnotic potency]. Additionally, not only was the trazodone group substantially smaller than the gabapentin group, there were [proportionally] significantly fewer males in the trazodone group. Also worth contemplating is the fact that gabapentin may be more useful for treating among persons with alcohol dependence due to the fact that its physiologic effect is more similar to alcohol than trazodone. Still, based on the preliminary results of this trial, it appears as though gabapentin is useful for the treatment of insomnia.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/12950711
2002: Gabapentin increases slow-wave sleep in normal adults.
Foldvary-Schaefer, Sanchez, Mascha, et al. (2002) discussed the fact that older antiepileptic drugs (AEDs) modulate numerous aspects of sleep. Specifically, older antiepileptic agents seemed to: increase light sleep, decrease slow-wave sleep (SWS), decrease REM sleep, and decrease sleep latency. Knowing that older antiepileptic drugs deleteriously affected sleep, the aforestated group of researchers sought to investigate the effect of gabapentin, a newer antiepileptic, on sleep.
For this reason, they organized a study and recruited 19 healthy adults – 9 of whom served as controls. All participants were assessed at baseline and endpoint with polysomnographic assessments and sleep scale questionnaires. After baseline measures were collected, 10 individuals were assigned to receive gabapentin and were titrated upwards to a maximum dosage of 1800 mg per day.
It was noted that 9 of 10 gabapentin recipients achieved maximum dosage of 1800 mg per day and the remaining individual administered 1500 mg per day due to experiencing unwanted dizziness at the 1800 mg dose. Results indicated that slow-wave sleep (SWS) significantly increased under gabapentin treatment as compared to baseline. Although there were no changes in other measures (e.g. sleep scale scores) under gabapentin treatment compared to baseline – there were modest decreases in arousals, awakenings, and sleep stage transitions.
Based on the results, researchers concluded that gabapentin may not disturb sleep as much as older antiepileptic drugs. While this study was limited by its extremely small sample size, it was clear that gabapentin improved sleep architecture based on polysomnographic data. Overall, this study supports the idea that gabapentin can enhance sleep in healthy adults.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/12460250
Limitations of research associated with Gabapentin for sleep & insomnia
There are numerous limitations associated with the research of gabapentin as an intervention for sleep disturbances and/or insomnia. Perhaps the most substantial limitation is that that there are zero randomized controlled trials (RCTs) with large numbers of participants that evaluated gabapentin for the treatment of sleep disturbances and/or insomnia over a reasonable duration. While smaller-scale and/or uncontrolled trials suggest that gabapentin improves sleep, the quality of the data is, in most cases, too low for clinical relevance. Other limitations associated with the research include: lack of adjunct evaluation, conflicts of interest, dosing protocols, and inconsistent participant demographics.
- Adjunct: Gabapentin may prove useful as an adjunct intervention for persons with a medical condition plus comorbid insomnia and/or sleep disturbances. That said, presently there is only 1 randomized controlled trial that evaluated gabapentin’s efficacy as an adjunct for insomnia and 1 case report that documented its adjunctive benefit. In the standalone randomized controlled trial, gabapentin was considered more effective than a placebo for the management of refractory insomnia among patients using SSRIs for major depression. In the case report, gabapentin was effective for the treatment of refractory insomnia associated with bipolar 2 disorder. While it appears as though gabapentin may be safe and efficacious for the treatment of insomnia as an adjunct, more research is necessary to strengthen preliminary findings and to investigate whether: dosage, co-administered agents, and/or specific diagnoses – influence its adjunct efficacy.
- Administration protocols: The research is also limited by the fact that it hasn’t directly compared various administration protocols of gabapentin. While it is most common for individuals to administer gabapentin at a frequency of 3-times per day for the treatment of a medical condition such as postherpetic neuralgia, some individuals may administer gabapentin 4-times per day, 2-times per day, or even 1-time per day. It should also be noted that while certain protocols may implement even dosing (e.g. 300 mg, 3 times per day), others may implement uneven dosing (e.g. 300 mg in the morning, 600 mg in the evening). Additional research is needed to know whether certain gabapentin administration protocols are more conducive to sleep enhancement than others.
- Dosage comparison: Another limitation associated with the research of gabapentin for the treatment of sleep disturbances and/or insomnia is that various dosages haven’t been directly compared for efficacy or tolerability. As of current, research suggests that certain individuals may derive therapeutic benefit from 300 mg gabapentin per night, 600 mg gabapentin per night, 900 mg gabapentin per night, and 1800 mg gabapentin per night. That said, it is unclear as to whether specific dosages of gabapentin may be more effective and/or tolerable than others for the treatment of sleep conditions.
- Format comparison: Although most research has evaluated standard immediate-release gabapentin for the treatment of sleep disturbances, one trial tested gabapentin ER (extended-release). Both the standard immediate-release and extended-release formats appear to effectively attenuate sleep disturbances, however, it’s possible that one format is superior to the other in terms of its effect on sleep architecture, tolerability, and/or overall efficacy. For this reason, it may be worth directly comparing each of the gabapentin formats to determine whether one might yield greater therapeutic benefit than the other.
- Incentive: Because gabapentin is available as a generic medication, there’s little incentive to prove its efficacy for the treatment of sleep disturbances and/or insomnia. Pharmaceutical companies are disinterested in funding research demonstrating that gabapentin effectively treats insomnia because they wouldn’t stand to see any return on an investment. Similarly, most researchers would prefer to allocate research funds towards developing and/or testing novel sleep-enhancing compounds on the basis that they may prove more effective and safer than gabapentin, as well as yield profits via patents or pharmaceutical company financing. While it would be nice to conduct a large-scale trial of gabapentin for the treatment of insomnia, there’s negligible incentive to do so.
- Participant demographics: Perhaps another limitation associated with the research is that participant demographics are inconsistent from trial to trial. Though there are numerous standalone trials demonstrating that gabapentin ameliorates sleep disturbances among persons with conditions such as: alcohol dependence, depression, fibromyalgia, neuropathic pain, primary insomnia – follow-up trials are lacking. The lack of follow-up trials makes it difficult to know whether gabapentin legitimately treats sleep disturbances in persons with any specific medical condition and/or establish relevant dosing protocols. Keeping participant demographics consistent [in regards to medical diagnoses] for multiple trials should prove helpful.
- Potential conflicts of interest: Although most papers highlighting the efficacy of gabapentin for the treatment of insomnia and/or sleep disturbances were devoid of conflicts of interest, a series of case reports was authored by an individual who stands to profit if gabapentin is approved and sold for the treatment of hot flashes. Because hot flashes are associated with menopause-related insomnia, it’s necessary to consider that the series of case reports documenting the efficacy of gabapentin for the treatment of insomnia may have been presented in such a way as to encourage future prescriptions and/or promote the drug’s prescription for premenopausal/menopausal hot flashes. That said, just because there’s a conflict of interest does NOT automatically indicate bias or hidden agendas.
- Sample sizes: Another limitation associated with the research of gabapentin for the treatment of sleep disturbances is that most trials had small numbers of participants. Whenever small samples are utilized in trials, the trial is considered “under powered” and there’s increased likelihood that the corresponding results (e.g. gabapentin enhances sleep) were a product of random chance. What’s more, when sample sizes are small plus study designs are poor (e.g. non-randomized, uncontrolled, etc.), odds that results were a product of random chance further increases. Additional trials with large numbers of participants (e.g. 100+) would suggest that the sleep enhancement effect of gabapentin is less attributable to random chance.
- Study designs: Most trials investigating the effect of gabapentin on sleep implemented poor designs. Of 7 trials published between 2002 and 2016 in which gabapentin was investigated for the treatment of sleep disturbances, only a few were randomized, controlled, and double-blinded. Failure to implement randomization, controlling, and/or blinding increases likelihood that the outcomes were subject to inaccuracies due to placebo effects and/or researcher-influence. As was already mentioned, many of these poorly designed studies were small-scale (with few participants), which further decreased the quality of data.
- Trial duration: Most trials investigating gabapentin’s efficacy for the treatment of sleep disturbances were conducted over a short duration. While some individuals may only need short-term relief from sleep disturbances, others may require longer-term treatment. The longest randomized controlled trial in which gabapentin was investigated for sleep disturbances was 12 weeks (~3 months). It’s necessary to acknowledge that the sleep enhancing effect of gabapentin might diminish and/or abate over a longer-term. For this reason, it may be worth conducting longer-term trials in which its effect on sleep is assessed.
Verdict: Gabapentin likely helps manage sleep disturbances for some indivdiuals
Upon analysis of the currently-available literature, it is apparent that all data are consistent in suggesting that gabapentin is safe, tolerable, and effective for the treatment of sleep disturbances and/or the enhancement of sleep. However, as was mentioned, there are numerous limitations associated with the research such as poor trial designs, small sample sizes, and/or limited trial duration. These limitations reduce the quality of data produced by trials such that it is not clinically relevant.
That said, not all trials of gabapentin for the treatment of sleep disturbances were conducted over a short-term with poor designs and small sample sizes. A few trials implemented randomized controlled designs, recruited a moderate-sized sample (e.g. 50+ participants), and were conducted over a longer duration (e.g. 4 to 12 weeks). In each of these well-designed, larger-scale, longer-term trials, significant sleep improvements were observed among gabapentin users – providing higher-quality evidence to suggest that gabapentin is an efficacious sleep aid.
Moreover, it is worth noting that polysomnography data were collected from participants in multiple trials, all of which revealed a favorable effect of gabapentin on sleep. Specifically, gabapentin enhanced slow-wave sleep plus sleep efficiency, and reduced spontaneous arousal index. Based on the fact that polysomnography data were consistent across trials (RCTs and non-RCTs), it’s likely that the favorable effect of gabapentin on sleep architecture was not attributable to a placebo response nor random chance.
Additionally, there are multiple case reports in which gabapentin was documented as effective in clinical settings for the treatment of frequent awakenings and refractory insomnia. Considering the unanimous efficacy of gabapentin in all trials and case reports for the treatment of sleep disturbances; the observable effect of gabapentin on sleep architecture via polysomnography; its inhibitory mechanism of action; and countless anecdotes suggesting that gabapentin improves sleep – it’s not farfetched to assume that gabapentin is useful for the treatment of sleep disturbances and/or sleep enhancement in a subset of the population.
Who may benefit from gabapentin for sleep?
It is unknown as to whether certain individuals are likely to derive greater therapeutic benefit than others from gabapentin for sleep enhancement. Considering the fact that gabapentin is FDA-approved for the treatment of postherpetic neuralgia and partial onset seizures, persons with either of the aforestated conditions who experience sleep disturbances may derive greatest benefit. That said, preliminary research suggests that gabapentin may significantly improve sleep among populations with medical conditions such as: anxiety disorder, bipolar disorder, fibromyalgia, major depression, and neuropathic pain. Moreover, it appears as though gabapentin can enhance sleep in healthy adults and menopausal women.
- Partial onset seizures: Gabapentin is approved as an adjunct for the treatment of partial onset seizures in adults and pediatrics. Anyone who experiences sleep disturbances associated with partial onset seizures may find that gabapentin prevents partial onset seizures whereby sleep disturbances are reduced. It’s also possible that gabapentin may prevent partial onset seizures while simultaneously enhancing sleep. Perhaps the sleep enhancement facilitated by gabapentin is a mechanism by which it prevents partial onset seizures.
- Postherpetic neuralgia: Individuals diagnosed with postherpetic neuralgia or shingles induced by the herpes zoster virus tend to experience burning pain throughout nerve fibers. This pain can be severe enough to cause insomnia and/or interfere with sleep maintenance. Treating the postherpetic neuralgia with gabapentin should simultaneously attenuate neuralgia-induced sleep disturbances.
- Neuropathic pain: It is common for individuals with neuropathic pain to experience insomnia and/or sleep disturbances. When the condition is untreated, nerve fibers transmit incorrect signals to pain centers whereby the individual experiences debilitating pain. The neuropathic pain can be severe enough to interfere with sleep onset and maintenance. Because gabapentin can treat neuropathic pain, research suggests that it inhibits neuropathic pain-related sleep disturbances.
- Insomnia: Persons diagnosed with insomnia may also derive sleep enhancing benefit from gabapentin. A proof-of-concept trial showed that gabapentin effectively treated primary insomnia in a group of 18 individuals over a 4-week duration. Other research has shown that gabapentin ameliorates comorbid insomnia among individuals with major depression and bipolar disorder. Because gabapentin exerts an inhibitory effect upon physiology, it should help persons with insomnia transition from wakefulness to sleep. Moreover, some suspect that gabapentin may be favorable over first-line sleeping medications in terms of tolerability.
- Anxiety disorder: Anxiety disorders are associated with sympathetic tone and excess excitatory and/or suboptimal inhibitory transmission – which often cause insomnia and sleep disturbances. The problem with anxiety-induced insomnia and/or sleep disturbances is that, if the anxiety is left unmanaged, it can exacerbate the sleep disturbances which creates a vicious circle. Because many benefit from gabapentin for anxiety, any reduction in anxiety should enhance sleep. Moreover, because gabapentin can improve sleep, this may help attenuate anxiety.
- Major depression: It is known that major depression can cause sleep disturbances, as well as that sleep disturbances and/or abnormal sleep architecture can induce major depression. Early research suggests that adjunct gabapentin may help treat insomnia among SSRI-medicated patients with major depression. Moreover, some individuals experience mood enhancement while under the influence of gabapentin, possibly another means by which it ameliorates depression-related insomnia.
- Premenopausal or menopausal: Many women experience sleep disturbances such as insomnia and/or frequent awakenings while premenopausal or menopausal. Case studies suggest that gabapentin taken once per night can attenuate insomnia and frequent awakenings among these women. Although the exact mechanism by which it improves sleep for premenopausal or menopausal women isn’t known, it might be due to the prevention of hormone fluctuation-induced sympathetic nervous system activation.
- Fibromyalgia: Individuals diagnosed with fibromyalgia typically experience widespread muscle pain and/or tenderness accompanied by a host of additional symptoms including fatigue, memory deficits, mood problems, and sleep disturbances. Evidence from a pilot study published in 2016 suggests that extended-release gabapentin may increase sleep duration and enhance sleep quality among persons with fibromyalgia. In this pilot study, gabapentin (ER) increased sleep duration by ~1.2 hours per night and improved subjective sleep quality over a 12-week duration. Not only might gabapentin directly improve sleep among patients with fibromyalgia, it may help manage other symptoms of the condition such as muscle pain and mood problems – which in itself, could lead to improved sleep.
- Bipolar disorder: It is thought that a subset of persons diagnosed with bipolar disorder may derive benefit from the administration of [adjunct] gabapentin for the treatment of sleep disturbances. A case report was documented in which a patient with bipolar 2 disorder experienced refractory insomnia despite attaining mood stabilization with a combination of carbamazepine and risperidone. Psychiatric professionals initially tested antipsychotics and benzodiazepines as adjuncts to combat the insomnia, neither of which proved useful. When gabapentin was added as the adjunct, it attenuated the insomnia plus provided mood enhancement. While this was nothing more than a standalone case report, it provides evidence to suggest that adjunct gabapentin may provide benefit to certain individuals with sleep disturbances associated with bipolar disorder.
- Substance withdrawal: Discontinuation of any psychoactive substance after an extended duration of usage can lead to sleep disturbances. Any sleep disturbances that emerge following discontinuation of psychoactive substances are usually a result of: sympathetic overactivation, circadian dysregulation, neurotransmitter / hormone imbalances, and/or specific withdrawal symptoms (e.g. anxiety). Due to gabapentin’s inhibitory action, it often combats sympathetic overactivation and excessive excitatory transmission, thereby reducing disturbing withdrawal symptoms and improving one’s sleep. Moreover, the sleep improvements derived from gabapentin during psychoactive substance discontinuation may expedite a person’s recovery or transition back to physiologic homeostasis. Research suggests that gabapentin may be especially effective for the preservation of sleep during alcohol withdrawal and opiate withdrawal. (For more information, read about the usage of Gabapentin for Opiate Withdrawal).
- Restless leg syndrome (RLS): A popular off-label use of gabapentin is for the treatment of restless leg syndrome, a condition characterized by a nearly-irresistible urge to move the legs. Because urges to move the legs typically emerge at night among RLS patients, the condition commonly causes insomnia and other sleep disturbances such as broken sleep and/or premature waking in the morning. Anecdotally, a subset of RLS patients claim that gabapentin completely mitigates the restless leg and/or reduces restlessness enough so that they can get a good night’s sleep. Interestingly, those who experience RLS-induced insomnia have been shown to release more glutamate in the thalamus than others. Knowing that gabapentin inhibits cortical glutamate release in animals, it’s possible that similar effects in humans mitigate RLS-induced insomnia.
- Healthy adults: Healthy adults who are devoid of any medical conditions may also benefit from taking gabapentin for sleep. Research in healthy adults discovered that gabapentin significantly increased slow-wave sleep, yet decreased nighttime awakenings, arousal, and sleep stage transitions. That said, if you’re healthy, it should never be encouraged to use a drug for sleep enhancement as it may lead to deleterious long-term outcomes. Moreover, even if there are no drawbacks, it’s debatable as to whether drug-induced sleep enhancement among healthy adults is ethical.
What dosage of gabapentin should you take for sleep?
Due to the fact that no large-scale randomized controlled trials have been conducted evaluating the effect of gabapentin on sleep, it’s unclear as to what the optimal dosage is for the treatment of sleep disturbances and/or sleep enhancement. If you’re using gabapentin off-label as a sleep aid, it’s recommended to work with a medical professional to optimize your dosing. A medical professional will be able to help you determine a safe dosage in accordance with your current medical diagnoses, medication and/or supplement regimen, and genetics.
To reduce likelihood of side effects, adverse reactions, and/or serious long-term effects, it’s generally smart to utilize the “minimal effective dose” or lowest quantity of gabapentin that provides therapeutic benefit. Finding the minimal effective dosage of gabapentin for sleep may involve initiating treatment at an extremely small (subtherapeutic) dose, and gradually titrating the dosage up [over a duration of days and/or weeks] to a level that attenuates sleep disturbances and/or facilitates sleep enhancement. Until further research is completed, guidelines cannot be formed for the administration of gabapentin for sleep. That said, we can analyze the available literature and discuss the dosages that appeared efficacious in preliminary trials.
- Adjunct: When administered as an adjunct to another neuropsychiatric medication (SSRIs), gabapentin effectively treated insomnia within the dosage range of 100 mg to 600 mg. As one might expect, adjunct dosages of gabapentin for sleep are relatively small due to potential synergism and/or interaction with other medications.
- Monotherapy: When administered as a standalone agent for the treatment of sleep disturbances and/or the enhancement of sleep, research suggests that gabapentin provides benefit within the dosage range of 300 mg to 1800 mg. While 300 mg may benefit some during an initial titration, most individuals respond better to dosages between 600 mg and 1800 mg for sleep.
Note: It is important to emphasize that the dosages facilitating therapeutic benefit in preliminary trials are not yet considered clinically relevant. Always work closely with a doctor to determine the safest dosage of gabapentin based on your medical history, medication and/or supplement regimen, and genetics.
Have you used Gabapentin for sleep or insomnia?
If you’ve used gabapentin to treat a sleep disorder such as insomnia or to enhance sleep, be sure to share your experience in the comments section below. In the event that you had to rate gabapentin’s hypnotic efficacy on a scale of 1 to 10 (with 1 being “least effective” and 10 being “highly effective”), which numeric rating would you assign it? If you believe that gabapentin significantly improves your sleep, in what specific ways do you find it most hypnotically efficacious?
Hypothetical answers may include: improves symptoms of a medical condition (e.g. neuropathic pain) that would normally disturb sleep; induces drowsiness at nighttime; reduces hyperarousal or anxiety in the evening; and/or a combination of all of the aforementioned answers (e.g. symptomatic reduction plus CNS downregulation). To help others get a better understanding of your situation, provide additional details such as: the dosage of gabapentin you regularly administer (e.g. 900 mg), the specific medical condition for which gabapentin was prescribed, the dosing regimen (e.g. once per night, twice daily, etc.), preexisting medical diagnoses (e.g. refractory insomnia), and other substances regularly used in addition to gabapentin (e.g. alcohol, dietary supplements, pharmaceutical medications, etc.). For persons who received gabapentin off-label for the management of a sleep disorder, were other hypnotics (i.e. sleep aids) first tested?
If other hypnotics were trialed prior to gabapentin, mention the number that were tested and how gabapentin [subjectively] compared in terms of hypnotic efficacy and tolerability. Also document the cumulative duration over which you’ve been using gabapentin and note whether you’ve experienced any unwanted side effects and/or long-term effects. If you’re a long-term gabapentin user, have you noticed onset of tolerance whereby you had to increase your dosage due to diminishing efficacy of a previous dosage?
In summary, not only do objective polysomnography recordings support the idea that gabapentin enhances sleep parameters, many users report substantial improvements in their sleep quality following gabapentin administration. While higher-quality data are needed to substantiate gabapentin’s hypnotic efficacy before it can be recommended as a sleep aid in clinical settings, it may be worth off-label consideration among persons: who don’t respond to conventional hypnotics; who cannot tolerate conventional hypnotics; who present medical conditions for which gabapentin is indicated – along with comorbid sleep disturbances; and/or who exhibit atypical presentations of sleep disorders.