Alprazolam (Xanax) is a fast-acting, medium-duration benzodiazepine that was patented in 1971 and approved for medical use in the U.S. in 1981.
As of 2019, alprazolam was the 41st most-prescribed medication in the U.S. with over 17M annual prescriptions.
It is commonly used for the short-term treatment of anxiety disorders, panic disorder, and generalized anxiety disorder – but occasionally used as an adjunct in the management of chemotherapy-related nausea.
Some alprazolam users have discovered that it seems to treat insomnia and/or enhance sleep quality.
Others have observed that it functions similarly to nonbenzodiazepine sleep meds (Z-drugs) like zolpidem and wonder why it’s not formally approved for insomnia.
How does alprazolam help sleep & treat insomnia? (Mechanisms)
GABA-A receptor PAM
Alprazolam functions as a positive allosteric modulator of GABA-A receptors. From binding to GABA-A receptors, alprazolam enhances the effect of “GABA” (gamma-amino-butyric-acid) – the most potent inhibitory neurotransmitter in the brain.
Specifically, when alprazolam binds to GABA-A receptors (ligand-gated chloride ion channels) – chloride ion channels open more frequently or for longer durations.
This allows for an influx of chloride ions within neurons which causes “hyperpolarization” (neurons become inhibited/less likely to fire).
The effects resulting from neuronal hyperpolarization (i.e. inhibition via GABA) include: amnesic, anxiolytic, anticonvulsant, hypnotic, myorelaxant, and sedative effects. Predictably, this helps reduce anxiety/stress and may cause sleepiness.
HPA axis suppression
Alprazolam suppresses the HPA (hypothalamic-pituitary-adrenal) axis.
As a secondary effect of its GABA-A receptor PAM, alprazolam activates the mesolimbic dopamine system – as evidenced by increasing cerebral blood flow (CBF) in the nucleus accumbens after a single dose. (R)
A study involving rats demonstrated that alprazolam increases both D1 and D2 dopamine receptors in the striatum. (R)
Note: I’d guess that downstream/secondary effects (e.g. dopaminergic effects) are not involved in the sleep inducing effect of alprazolam – but it’s possible that they play some role.
Alprazolam for Sleep & Insomnia (Research)
Asghar et al. (2020): “Melatonin use has shown better sleep quality and less insomnia severity as compared to alprazolam use in our study.” (R)
- 117 hemodialysis-dependent patients with end-stage renal disease (ESRD) received alprazolam 0.5 mg nightly (N=79) or melatonin 3 mg nightly (N=38).
- Sleep assessments included: PSQI, ESS, ISI, SSS.
- Both groups of patients had similar lab markers except: higher hemoglobin in melatonin users & high parathyroid hormone in the alprazolam group.
- Results: PSQI scores were 8.76 (alprazolam) and 7.32 (melatonin). In sub-scores there were no differences in sleep latency or daytime dysfunction. Differences in sleep efficiency and subjective sleep quality were not statistically significant. ESS scores found no significant differences between groups.
- Significant differences: Lower sleep duration and sleep disturbances in melatonin users. Higher ISI and SSS scores occurred for the alprazolam users.
- 89 participants reported “poor sleep quality”: 81% used alprazolam & 65% used melatonin.
- 50 participants reported excessive daytime sleepiness: 45% used alprazolam & 36% used melatonin.
- 54% of alprazolam users had moderate insomnia vs. 50% of melatonin patients had sub-threshold insomnia.
What does this study suggest? Melatonin may be a better intervention for sleep disturbances among hemodialysis patients with ESRD than alprazolam.
Canham & Rubinstein (2015): Experiences of Sleep & Benzodiazepine Use among Older Women (R)
- Semi-structured interviews were conducted with 12 women (65-92) who used a benzodiazepine for 3+ months to treat a sleep disturbance.
- 7 of the 12 women used alprazolam (0.25 mg to 0.5 mg) between 9 months and 40+ years.
- 12 years
- 15 years
- 4-5 years
- 5 years
- 10-20 years
- 9-10 months
- 40+ years
- When questioned about alprazolam, a few responded:
- “Let’s me sleep.”
- “Every once in a while, when it [alprazolam] doesn’t work fast enough for me to get to sleep, I turn on the radio.”
- One woman described how alprazolam improves sleep which enables her to cope with caregiving responsibilities.
What can we learn here?
Either alprazolam continues to offer some degree of sleep enhancement with chronic/long-term use among old women – or these women have developed full-blown tolerance to its effect such that they now need it to fall asleep. The good thing is that most seem to be on relatively low doses and only use it at night.
Barbanoj et al. (2005): Compared the effects of alprazolam, paroxetine, alprazolam-paroxetine (combination), and placebo on sleep in healthy volunteers. (R)
- 22 healthy young volunteers with no history of sleep problems participated in a double-dummy, placebo-controlled, repeated-dose, 4-period, crossover study.
- All participants received all 4 treatment sequences: paroxetine-alprazolam placebo (PAP); paroxetine placebo-alprazolam (PPA); paroxetine-alprazolam (PA); paroxetine placebo-alprazolam placebo (PLA) – in randomized order.
- Each treatment was administered for 15 consecutive days with a treatment-free interval of 7 days prior to the subsequent study period.
- One PSG sleep study was performed on the first night (single-dose effects) and another was performed on the 15th night (repeated-dose effects).
- Subjective ratings for sleep quality, awakening quality, and early morning behavior were collected.
- Results: Our focus here is on PPA (standalone alprazolam).
- Decreases in latency to Stage 1 and Stage 2 of sleep were observed.
- Stage 2 sleep increased significantly on the first and last night.
- Slow-wave sleep (minutes & % total sleep time) decreased.
- On the first night, increased total sleep time (TST), total sleep period (TSP), and sleep efficiency index (SEI) – were observed.
- Self-assessment of awakening quality was impaired.
- Significant increases in subjective sleep latency were observed after stopping alprazolam.
Hindmarch et al. (2005): Double-Blind Study to Assess Effects of Alprazolam vs. Pregabalin vs. Placebo on Sleep (R)
- 12 healthy adults received: pregabalin (150 mg, t.i.d.); alprazolam (1 mg, t.i.d.); placebo (t.i.d.) for 3 days.
- Measures: Objective sleep (polysomnography) & subjective sleep (questionnaire).
- Results: Alprazolam significantly reduced slow-wave sleep (SWS), modestly reduced sleep onset latency, and reduced REM as a proportion of total sleep time.
Saletu-Zyhlarz et al. (2000): Insomnia in Panic Disorder: Placebo-Controlled Trials with Alprazolam (R)
- An acute, placebo-controlled, crossover design study involved administration of alprazolam (0.5 mg) vs. placebo – in patients with insomnia associated with panic disorder.
- Measures: Polysomnography & psychometry.
- Results: Alprazolam increased sleep efficiency, total sleep time (TST), snoring, and Stage 2 sleep; decreased wakefulness during the total sleep period; reduced Stage 3 & 4 sleep; reduced oxygen desaturation and periodic leg movements; improved subjective sleep quality; reduced somatic complaints, drive, affectivity, and drowsiness in the morning.
- No changes were observed in REM variables.
- Conclusion: Alprazolam significantly improves aspects of sleep in patients with insomnia associated with panic disorder. Whether the improvements can be maintained with regular treatment remain unclear (due to possible tolerance onset).
Zarcone Jr. et al. (1994): Alprazolam decreased slow wave sleep (SWS), increased REM latency, decreased REM in: minutes, percent (%), and REM sleep “eye movements.” (R)
- Alprazolam was administered for 43 days in doses of 6-10 mg per day to 9 patients with depression.
- In 4 of the 9 patients, alprazolam generated a significant antidepressant effect.
- A general trend was observed toward “increased total sleep time” (but this was not statistically significant).
- Nonsignificant changes in concentrations of 3-methyl-4-hydroxyphenylglycol and homovanillic acid in the cerebrospinal fluid (CSF) were similar to those observed following treatment with tricyclic antidepressants.
- Baseline sleep and CSF metabolites did NOT predict the therapeutic effects of alprazolam.
Note: Because I do not have access to the full-text of this paper, it’s unclear as to whether alprazolam improved sleep quality OR merely improved depression in a subset of patients which resulted in changes in sleep architecture.
Jurado et al. (1989): “Effects of 1-week Administration of 2 Benzos on Sleep & Early Daytime Performance” (R)
- Subjects: 6 healthy male volunteers
- Analyzed the effect of 1-week of alprazolam (0.25 mg/day), lorazepam (1 mg/day), and placebo – on sleep and residual effects upon awakening.
- Design: Crossed, double-blind.
- Results: There were no significant objective (polysomnography) differences on sleep parameters from benzodiazepines relative to placebo. Benzodiazepines could have residual effects on attention, but in this study attentional deficits were only noted from lorazepam not alprazolam.
What can we learn here? Healthy subjects do not benefit from benzodiazepines for sleep enhancement – and may experience residual attentional deficits.
Kales et al. (1987): “The clinical utility of alprazolam when administered to insomniac patients appears to be limited because of a relatively rapid development of tolerance and possible disinhibitory reactions during drug use and the occurrence of rebound insomnia following withdrawal.” (R)
- 6 individuals with chronic insomnia (23-62 years old) participated in a 16-night sleep study which included: (A) 4 placebo-baseline nights followed by (B) 7 nights of alprazolam (1 mg) and (C) 5 placebo-withdrawal nights.
- On the first 3 drug nights, alprazolam was highly effective for: (1) inducing sleep and (2) maintaining sleep – as determined by objective data (EEG, EMG, EOG) and subjective reports.
- Alprazolam suppressed slow wave sleep (Stage 3 and deeper) and produced a compensatory increase in Stage 2 sleep – with slight suppression of REM (rapid-eye movement) sleep.
- Subjective reports revealed improvement in sleep latency and total sleep time (which aligned with objective analyses).
- After 1-week of administration, alprazolam had lost ~40% of its efficacy.
- During alprazolam usage, one participant reported difficulty controlling expression of inappropriate emotions when interacting with others (indicative of disinhibition).
- On the third night after cessation, there was a significant increase in sleep difficulty above baseline levels (i.e. rebound insomnia).
Subhan et al. (1986): Alprazolam and lorazepam increased subjective reports of sedation, reduced sleep onset latency, and improved sleep quality. (R)
- Alprazolam (0.5 mg), lorazepam (2 mg), and placebo – were evaluated in 12 healthy volunteers in a randomized, double-blind, crossover study.
- Non-sleep measures: Alprazolam reduced critical flicker fusion threshold (CFFT) relative to baseline – a psychomotor evaluation – whereas lorazepam caused greater overall impairment in CRT, tracking accuracy, and CFFT.
Seidel et al. (1985): Effect of Alprazolam & Diazepam on Daytime Sleepiness in Non-Anxious Subjects. (R)
- Alprazolam was far more sedating than diazepam on Day 1, but not more on Day 7.
- Significant tolerance to daytime sedation developed during the first treatment week with alprazolam (0.5 mg, b.i.d.) – whereas level of sedation in diazepam treatment remained unchanged.
- Results suggest that tolerance to alprazolam’s sedative effect (which develop during the first week) may be distinct from tolerance to its anxiolytic effects (which develop after at least 4 weeks).
What can we learn here? Alprazolam’s sedating effect seems to diminish within 7 days of twice daily administration. It remains unclear as to whether it would diminish with just once daily administration (e.g. bedtime usage).
Bonnet et al. (1981): “Alprazolam showed significant effects on REM sleep parameters and might be evaluated for possible antidepressant effect.” (R)
- 8 healthy young males received 3 doses of alprazolam (0.25 mg, 0.5 mg, 1 mg) and placebo – while a second group of 8 healthy young males received 3 doses of diazepam (2 mg, 5 mg, 10 mg) and placebo in the same design.
- All subjects slept in the laboratory for 10 nights (2 consecutive nights each week for 5 consecutive weeks).
- The first 2 nights served as “adaptation” and during the subsequent 4 weeks – subjects received a random dose of alprazolam (or placebo) or diazepam (or placebo) each week.
- Similar dose-related benzodiazepine effects were observed with both drugs.
- Alprazolam: reduced Stage 4 sleep (%) & REM sleep (%) and increased Stage 2 sleep (%).
- Diazepam: Decreased Stage 1 sleep (%) and increased Stage 2 sleep (%).
What can we learn here? Alprazolam appears to affect sleep in different ways than diazepam, but this study is limited by its small sample size. Potential antidepressant effects were suggested due to alprazolam’s effect on REM (akin to antidepressant medications).
Itoh et al. (1980): An open-label study with 115 neurotic patients reported that alprazolam 0.4-3.2 mg (~1.4 mg) for 4 weeks produced a “slight-to-remarkable” improvement in sleep quality without serious side effects. Improvements were most significant among patients with severe initial sleep disturbances. (R)
Wang et al. (2019): “Alprazolam and bailemian capsule improves the sleep quality in patients with post-stroke insomnia.” (R)
- 231 stroke patients
- Retrospective study (3 weeks)
- Alprazolam vs. Bailemian vs. Alprazolam + Bailemian (combo)
- Measures: PSQI & polysomnography
- Results: Alprazolam significantly improved sleep efficiency & decreased arousal times, REM sleep, and sleep latency. Bailemian improved sleep efficiency, total sleep time, and duration of N3. (ALP + BC combination improved sleep to a greater extent than either as a standalone).
Other studies (not entirely on topic)…
Khare et al. (2018): Oral melatonin (6 mg) when used as a premedication (before surgery) is an effective alternative to alprazolam in providing anxiolysis with less sedation – along with maintenance of cognitive and psychomotor function. (R)
- 90 adult patients received either: melatonin (6 mg); alprazolam (0.5 mg); or placebo (multivitamin).
- Measures: Anxiety, sedation, orientation, cognitive function.
- Results: Both melatonin (6 mg) and alprazolam (0.5 mg) significantly reduce anxiety compared to a placebo. Sedation was higher with alprazolam than melatonin. Cognitive function was better with melatonin than alprazolam and placebo. (Cognitive difference likely explained by: alprazolam-related sedation & placebo’s failure to reduce anxiety – which is detrimental to cognition.)
What can we learn here? Melatonin is capable of reducing pre-surgery anxiety just as well as alprazolam but produces significantly less sedation and doesn’t impair cognition (alprazolam does). However, based on results here – one might argue that alprazolam would be superior for sleep induction/maintenance than melatonin given its ability to increase sedation.
Pokharel et al. (2014): “While melatonin alprazolam combination reduced anxiety better than either drug alone, it produced sedation and amnesia to a similar degree as alprazolam alone.” (R)
- Evaluated if the addition of melatonin to alprazolam has superior premedication effects vs. each agent as a standalone in 80 adult patients with anxiety.
- Doses were as follows: alprazolam (0.5 mg) + melatonin (3 mg); alprazolam (0.5 mg); melatonin (3 mg); placebo.
- Measures: Change in anxiety and sedation score at 15, 30, 60 minutes post-medication and changes in memory function (memory loss).
- Results: Alprazolam (0.5 mg) + melatonin (3 mg) generated superior anxiety reduction than either agent as a standalone (indicative of synergistic anxiolysis). Adding melatonin to alprazolam did NOT worsen sedation score or amnesic effects.
- Adverse reactions were similar in all groups – suggesting that combining melatonin and alprazolam (at the dosages used in this study) do not increase side effects.
What can we learn here?
That combining low-dose alprazolam with reasonably-dosed melatonin appears effective and tolerable for anxiety reduction in adults as premedication (before surgery). That said, this study did NOT evaluate effects of these agents on sleep.
We know that the combination did NOT increase sedation more than either used in isolation. This means that adding melatonin to alprazolam (at the dosages in this study) doesn’t appear to increase sleepiness.
However, one might infer that if anxiety is interfering with sleep – then concomitant administration of alprazolam + melatonin might improve sleep more substantially than each as standalone agents due to the greater anxiolysis derived from combination.
Schenck & Mahowald (1996): “Long-term nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep resulted in sustained efficacy in most cases, with low risk of dosage tolerance, adverse effects, or abuse.” (R)
- A total of 170 adult referrals over a 12-year period with longstanding sleep disorders (sleepwalking, sleep terrors, REM sleep behavior disorder, chronic/severe insomnia, and RLS/PLM disorders) who had been taking benzodiazepines for 6+ months were evaluated.
- Data from this study on the treatment of chronic severe insomnia (small % of insomnia patients) is not generalizable to the typical insomnia patient.
- A total of 136 patients (of the 170) received clonazepam nightly and no change in dose was needed in 6 months to maintain effectiveness – similar outcomes were documented with alprazolam and other benzodiazepines.
Singh & Kumar (2008): “Alprazolam might produce protective effect by involving GABAergic system against sleep deprivation-induced behavior alterations and related oxidative damage.” (R)
- Evaluated the effect of alprazolam on 72-hour sleep deprivation-related behavioral alterations and oxidative damage in mice.
- Sleep deprivation caused anxiety-like behavior, weight loss, impaired ambulatory movements, and oxidative damage as evidenced by increases in lipid peroxidation, nitrite level, and depletion of reduced glutathione & catalase activity in the brains of mice.
- Alprazolam administration (0.25 & 0.5 mg/kg, I.P.) significantly improved behavioral alterations.
- Alprazolam treatment restored depleted reduced glutathione & catalase activity AND reversed elevated lipid peroxidation & nitrite levels.
What can we learn here? Unclear if similar effect in humans (this was a mouse study). If effect is similar, then alprazolam may be useful in the treatment of abnormalities associated with sleep deprivation.
Does the research suggest that alprazolam treats insomnia & improves sleep?
Yes – but only if administered infrequently or for short durations (e.g. 3 days or less) such as to avoid physiological tolerance.
Research by Kales et al. (1987) indicates that alprazolam works extremely well for about 3 consecutive nights in patients with insomnia, but loses its efficacy by ~40% within 1 week of administration.
Furthermore, repeated usage of alprazolam is associated with tolerance onset and withdrawal symptoms, including rebound insomnia (i.e. worse sleep than before alprazolam), can be severe.
For this reason, alprazolam (and other benzodiazepines) are NOT formally approved for the ongoing treatment of insomnia.
That said, it remains unknown as to whether long-term usage of alprazolam for sleep results in complete tolerance or partial tolerance. If it only loses ~40% of its efficacy with continuous dosing – but doesn’t exceed this degree of loss, it might remain useful to some extent.
Furthermore, there are some cases of patients with chronic anxiety disorders (e.g. panic disorder) and/or severe insomnia wherein tolerance does not seem to occur (as evidenced by long-term usage and subjective reports of sustained efficacy at the same low doses as when first prescribed).
In healthy individuals without anxiety or insomnia – there is no significant “sleep enhancing” effect of alprazolam relative to placebo.
Benefits of alprazolam for sleep & insomnia (Possibilities)
- Higher quality sleep: Subjective sleep quality may improve significantly when using alprazolam due to the combination of anxiety reduction and sedation. Objectively sleep may also improve significantly among individuals with certain anxiety disorders and sleep disorders.
- Effective when used infrequently: Select studies indicate that alprazolam effectively improves aspects of sleep when used on an infrequent basis (e.g. a few times a week or less).
- Useful for maintenance insomnia: Individuals who wake up in the middle of the night and struggle to fall back asleep may find alprazolam highly effective due to its rapid onset of action and limited duration of action.
- Anxiety-related insomnia (?): Multiple studies have suggested that alprazolam may be beneficial in patients with anxiety disorders. It seems as though alprazolam offsets deleterious changes in sleep architecture associated resulting from anxiety – essentially normalizing sleep patterns.
- Neurosis-related insomnia (?): A study with 115 neurotic patients found that alprazolam (0.4-3.2 mg) for 4 weeks significantly improved sleep among patients with initially severe sleep disturbances. (R)
- Increased sleep time & efficiency: Select studies have found alprazolam useful for increasing total sleep time and sleep efficiency.
- Fewer nighttime awakenings: Alprazolam may decrease the total number of nighttime awakenings due to a combination of its anxiolytic and sedative effects.
- Refractory sleep disorders (?): One study found that benzodiazepines (including alprazolam) were effective for the treatment of refractory sleep disorders such that they could be used long-term in a subset of patients with severe insomnia without tolerance onset (and dosage increases).
- No tolerance in severe sleep disorders (?): Some research indicates that a subset of patients with severe sleep disorders may not develop tolerance to alprazolam – even when administered chronically (i.e. nightly) for a long-term. It’s possible that similar “lack of tolerance onset” might also be observed in patients with severe anxiety disorders.
- RLS-related sleep disturbances (?): Some research suggests that alprazolam may be useful in treating disturbed sleep associated with RLS, primarily by treating the RLS. (R)
- Offset sleep deprivation: In an animal model, alprazolam significantly attenuated: (1) increased oxidative stress; (2) behavioral changes; (3) anxiety increases – as a result of 72-hour sleep deprivation. It’s possible something similar might occur in sleep deprived humans.
Drawbacks & risks of alprazolam for insomnia (Possibilities)
- Adverse reactions: Adverse reactions associated with alprazolam include drowsiness, dizziness, memory problems, balance problems, slurred speech, difficulty concentrating, diarrhea, constipation, headache, nausea, upset stomach, vomiting, low libido, etc. (R)
- Addiction & dependence (?): Alprazolam can increase dopamine release in the mesolimbic reward pathway, which can induce a sense of “pleasure” – and in some cases this causes addiction. Regular use of alprazolam may induce psychological/physiological dependence such that some users end up “needing” the drug just to maintain normal sleep and function.
- Better alternatives: Evidence suggests that there are far better alternatives to alprazolam for the management of insomnia in terms of: proven efficacy and safety. Even other benzodiazepines like temazepam are considered better options.
- Brain fog & cognitive impairment: Some alprazolam users will experience a combination of “brain fog” (unclear thinking, disorganized thoughts, spaced out) and cognitive impairment (attentional deficits, memory problems, poorer decision making, slowed thinking, etc.) – as a result of using it for sleep.
- Duration of effect: Too short for sustained sleep of 7+ hours in some cases (particularly with immediate-release formats). The extended-release (XR) version of alprazolam provides a longer duration of effect but for many who only need alprazolam for sleep – the XR version is “too long acting” and will interfere with daytime functioning/performance.
- Rapid tolerance onset: Since the 1980s researchers have known that alprazolam causes rapid tolerance onset – particularly when administered every night for the treatment of insomnia. After one week of nightly administration, alprazolam loses ~40% of its effect. (R)
- Interactions & contraindications: Alprazolam is metabolized by CYP3A4 meaning it can interact with many other drugs such as erythromycin, fluvoxamine, ketoconazole, ritonavir, etc. Combining alprazolam with other CNS depressants (e.g. alcohol) could cause coma, respiratory depression, and possibly death. Certain medical conditions (e.g. pulmonary disease) are contraindicated with alprazolam.
- Long-term effects: Long-term administration of benzos like alprazolam may increase risk of dementia and early cognitive decline in adults. There’s some evidence that benzos like alprazolam may increase the risk of hip fracture in older adults by ~50%.
- Memory problems: In healthy male volunteers, chronic alprazolam intake impairs memory. (R) Many types of memory including working memory, short-term memory, long-term memory – formation and retrieval/recall may be interfered with.
- Nightmares, weird dreams, vivid dreams: Due to the effect of alprazolam on neurochemistry, brain waves, brain region activation, and sleep architecture – it may trigger nightmares, weird dreams, and/or vivid dreams – which some individuals may find upsetting.
- Neuropsychiatric reactions: Alprazolam might cause adverse neuropsychiatric reactions such as: anger, agitation, depression, attentional deficits, memory problems, etc. – in susceptible individuals.
- Not medically approved for sleep: Alprazolam is not FDA approved for the treatment of insomnia because there’s a lack of strong evidence showing that it’s safe and effective for this condition.
- Not for regular use: To get the most out of alprazolam for sleep – it should not be used regularly. Evidence suggests that tolerance onset may be rapid for all but a rare subset of individuals.
- Paradoxical reactions: Aggression, mania, agitation, hyperactivity, restlessness, rage, hostility, twitches, and tremor – may occur among individuals with paradoxical reactions (or responses that are opposite of what is expected).
- Psychomotor impairment: Use of alprazolam may increase risk of next-day motor vehicle accidents (MVAs). This is because the drugs tend to impair fine motor skills – and these impairments can persist the morning or entire day after administration.
- Rebound insomnia: If administered every night for the management of insomnia, alprazolam not only loses its effect rapidly – but stopping the medication can cause significant rebound insomnia (i.e. worse insomnia than before alprazolam was used).
- Residual (next-day) effects: Fatigue/lethargy, psychomotor impairment, and brain fog/cognitive impairment – are all common residual “next-day” effects that may result from alprazolam. Users of alprazolam should not drive motor vehicles or operate heavy machinery under its influence if residual effects occur.
- Unnatural sleep architecture: Polysomnography reveals that alprazolam can: (1) reduce slow-wave sleep (Stage 3 & 4); (2) increase REM latency; (3) decrease REM (minutes, %, # of REMs); (4) increase Stage 2 sleep; and (5) decrease latency to Stage 1 & 2 sleep.
- Withdrawal symptoms/syndrome: Because of its shorter half-life (~11 hours) than other benzos, alprazolam tends to pack a serious punch for withdrawal symptoms. Withdrawal symptoms include: anxiety, malaise, weakness, insomnia, tachycardia, dizziness, etc. – even after a careful 4-week taper.
- Worse sleep: Alprazolam may worsen sleep both subjectively and objectively. Sleep architecture changes might be disadvantageous in certain ways.
How I discovered alprazolam for insomnia…
I was prescribed alprazolam to be administered on an “as needed” basis years ago for anxiety. I almost never actually used it so it sat around and I honestly forgot that I even had the bottle.
This past year I’ve been dealing with sleep maintenance insomnia after COVID (and I’m not implying COVID is the cause – I actually think it was more of a coincidence). I do NOT consume any caffeine or use any psychostimulants throughout the day.
Occasionally I’ll wake up in the middle of the night, use the bathroom, return to bed – and be unable to fall back asleep… not even sure why (I feel tired and braindead/zombified but body doesn’t shut back down).
Sometimes meditation gets me back to sleep: 10 deep slow breaths, full body scan, breath counting, light visualization exercise, paced breathing, etc.
One night I decided to try using low-dose alprazolam instead of other things like diphenhydramine, valerian, kava, 5-HTP, chamomile/apigenin, clonidine, etc. – and surprisingly it worked incredibly well (so much so that it felt like I was “suddenly out” from anesthesia).
I do NOT consume alcohol ever so I think this improves its effect. If I’m not asleep within ~30 minutes I do NOT hesitate to administer alprazolam (0.25 mg) and this overrides my insomnia and has me asleep before I know it (my guess is within 15 minutes).
Note: Yes, I’ve tried “CBD” and its sedative/hypnotic effect is almost nonexistent. Its anxiolytic effect is extremely modest as well (I’m skeptical that it would beat a placebo in trials).
How I use alprazolam for sleep & insomnia…
I only use alprazolam for the management of occasional/intermittent “sleep-maintenance insomnia” (also called “middle insomnia”).
For this condition it seems to work flawlessly and better than any substance I’ve tried (including: diphenhydramine, clonidine, GABA, chamomile/apigenin, melatonin, valerian, 5-HTP, hops, lavender, magnesium glycinate/threonate/citrate, etc.).
Low dose: I use an extremely low dose or the “lowest effective dose” for a variety of reasons: (1) less significant side effects; (2) no significant grogginess upon waking; (3) less significant neurochemical modulation (lower tolerance, etc.). My dose is 0.25 mg – seems to work well.
Infrequently: I never use alprazolam 2 nights in a row – even if I have the urge to do so. Why? Because I don’t want to become tolerant to its effect. I did use it once 2 nights in a row and it was noticeably less effective on the second night. I take a minimum of several days between uses.
Standalone: These days I only use alprazolam as a standalone agent – nothing with it (including before its administration – I’m not using any other substances). Why? To minimize interaction risk and to allow alprazolam to work properly (some meds may disrupt or override its effect).
Maintenance insomnia (early awakening): I only take alprazolam if I wake up in the middle of the night (such as after 5 hours) and need more sleep but cannot fall back asleep after 30 minutes of meditation in bed. Sometimes the meditation works well – but other times I need a boost (and the alprazolam works like a charm).
Note: I’ve tried “rigid sleep hygiene” schedules for insomnia treatment and they do NOT work well for me. I never have difficulty falling asleep either.
Should you use alprazolam for sleep & insomnia?
Probably not. It’s not approved for the enhancement of sleep or treatment of insomnia.
Ask a medical doctor whether it would be safe and/or effective in your particular case.
I spoke with a doctor about using benzodiazepines intermittently for my maintenance insomnia and he stated that other benzodiazepines – particularly clonazepam (what he recommended) would be a better choice.
The half-life of alprazolam (~11 hours) is significantly less than clonazepam (30-40 hours) – so perhaps this is why – fewer withdrawal symptoms.
However, I personally prefer medications with shorter half-lives when I don’t use them daily and my goal is to eke out just 2-3 hours of extra sleep.
Formats of alprazolam for sleep & insomnia…
- Extended-release (XR): For primary and maintenance insomnia – maintains constant levels 5-11 hours after dosing.
- Immediate-release: For primary OR maintenance insomnia (such as administering during the middle of the night after wakeup). This is what I use… I don’t want to be under the influence of alprazolam for any longer than necessary.
What’s the best dosage of alprazolam for insomnia?
I think the minimum necessary amount.
This will differ for everyone depending upon severity of insomnia and cross-tolerance with other GABAergic medications or alcohol.
In someone who drinks alcohol regularly, lower doses of alprazolam may be less effective or ineffective due to cross-tolerance.
Will you become tolerant to alprazolam for insomnia?
It depends how often you use it. Most people won’t develop tolerance to alprazolam if they use it infrequently (once or twice a week) for occasional insomnia. However, if you use it frequently (e.g. daily or even every-other-day) you may become tolerant to its effect.
Note: If you use any other GABAergic substances you may also become tolerant to its effect via cross-tolerance.
How does alprazolam compare to alcohol (ethanol) & Z-Drugs (nonbenzodiazepines)?
Alcohol works through ligand-gated ion channels and primarily functions as a positive allosteric modulator of GABA-A receptors like benzodiazepines.
(Other less significant actions of alcohol occur at: ionotropic glutamate AMPA kainate receptors, NMDA receptors, glycine receptors, nicotinic acetylcholine receptors, 5-HT3 receptors, voltage-gated calcium channels, BK channels, etc.).
Nonbenzodiazepines (Z-drugs) like zolpidem function as positive allosteric modulators of GABA-A receptors – and are relatively indistinguishable from benzodiazepines in terms of neurochemical actions.
That said, nonbenzodiazepines have more research supporting safety and efficacy for the enhancement of sleep and treatment of insomnia than both alcohol and benzodiazepines – and thus are preferred.
Have you used alprazolam for insomnia?
If you’re like me and have used alprazolam for the treatment of insomnia or the enhancement of sleep, feel free to drop a comment about your experience… Details may be helpful such as:
- Frequency of alprazolam usage (e.g. once a week)
- Dosage of alprazolam
- Type of insomnia you have (or whether you just use it to enhance sleep)
- Whether you drink caffeine or use other substances (that might disrupt sleep)
- Whether you take drugs, medications, supplements with it (might influence its efficacy)
- Medical conditions that may influence its effect
Do you find alprazolam useful for insomnia? If you use it for insomnia – do you believe you’ve become tolerant to its effect or experienced physiological dependence?