Short-term Treatment Of Insomnia Research Articles

Solvent effects on the absorption and fluorescence spectra of Zaleplon: Determination of ground and excited state dipole moments

Solvent effects on the absorption and fluorescence spectra of Zaleplon, a nonbenzodiazepine sedative/hypnotic drug that is mainly used for the short term treatment of insomnia, were investigated in 18 different solvents with diverse polarities. Dipole moments of the ground and excited state (μg and μe) were determined by Lippert-Mataga, Bakhshiev, Reichardt, McRae and Suppan solvatochromic methods. The dipole moment of Zaleplon ground state in the gas phase has been calculated as μg = 10.95 D (TD-DFT) with B3LYP/cc-pVTZ functional. There is a good agreement of theoretical data with Reichardt, McRae, and Suppan correlations, while some dissidence with Lippert-Mataga and Bakhshiev equations is suggesting the occurrence of specific solute-solvent interactions. Additionally, multiple linear regression analysis with Kamlet-Taft and Catalan solvatochromic models was applied to solute-solvent interactions. Dominant property of the solvent that affects the absorption band and Stokes shifts of Zaleplon is polarity of the solvent while the emission band is influenced mainly by solvent basicity.

Zopiclone versus placebo for short-term treatment of insomnia in patients with advanced cancer: study protocol for a double-blind, randomized, placebo-controlled, clinical multicenter trial

BackgroundDespite the high prevalence of insomnia in patients with advanced cancer, there are no randomized controlled trials on pharmacological interventions for insomnia in this group of patients. A variety of pharmacological agents is recommended to manage sleep disturbance for insomnia in the general population, but their efficacy and safety in adults with advanced cancer are not established. Thus, there is a need to evaluate the effectiveness of medications for insomnia in order to improve the evidence in patients with advanced cancer. One of the most used sleep medications at present in patients with cancer is zopiclone.MethodsThis is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 100 patients with metastatic cancer who report insomnia will be randomly allocated to zopiclone or placebo. The treatment duration with zopiclone/placebo is 6 consecutive nights. The primary endpoint is patient-reported sleep quality during the final study night (night 6) assessed on a numerical rating scale of 0–10, where 0 = Best sleep and 10 = Worst possible sleep. Secondary endpoints include the mean patient-reported total sleep time and sleep onset latency during the final study night (night 6).DiscussionResults from this study on treatment of insomnia in advanced cancer will contribute to clinical decision-making and improve the treatment of sleep disturbance in this patient cohort.Trial registrationClinicalTrials.gov, NCT02807922. Registered on 21 June 2016.

Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials

ObjectiveTo assess the efficacy and tolerability of trazodone compared with placebo in patients with insomnia. MethodsElectronic databases were searched and relevant reports were hand-screened to identify eligible trials. Only randomized placebo-controlled trials were included. Standardized mean differences (SMD) and the odds ratios (OR) were estimated using a random-effect model. Primary efficacy outcomes included sleep efficiency (SE%) and self-reported sleep quality (SQ). Secondary efficacy outcomes included sleep latency (SL), total sleep time (TST), the number of awakenings (NAs), waking time after sleep onset (WASO). Tolerability outcome was measured by the number of patients who discontinued for adverse events and acceptability outcome was measured by the number of patients who discontinued for all causes. ResultsSeven trials involving 429 patients were included. There was no significant improvement for trazodone in SE% (SMD = 0.09, 95% confidence interval (CI) −0.19 to 0.38, P = 0.53) with a non-significant heterogeneity (I2 = 0%, P = 0.59). However, patients receiving trazodone perceived better SQ than those receiving the placebo (SMD = −0.41, 95% CI −0.82 to −0.00, P = 0.05) with a non-significantly moderate heterogeneity (I2 = 65%, P = 0.06). As to secondary efficacy outcomes, we only found a significant reduction for trazodone in NAs (SMD = −0.51, 95%CI −0.97 to −0.05) compared to the placebo, with non-significant differences found in SL, TST, or WASO between trazodone and placebo. Moreover, no significant difference was found in the outcome of tolerability or acceptability. ConclusionsTrazodone was effective in sleep maintenance by decreasing the number of early awakenings and it could significantly improve perceived sleep quality, although there were no significant improvements in sleep efficiency or other objective measures. Trazodone however, presented good tolerance in the short-term treatment of insomnia.

European guideline for the diagnosis and treatment of insomnia.

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Clinical Sleep-Wake Disorders II: Focus on Insomnia and Circadian Rhythm Sleep Disorders.

Insomnia and circadian rhythm sleep disorders affect large proportions of the population and have pronounced effects on quality of life and daytime performance. While the neurobiology of insomnia is not yet fully understood, circadian rhythm sleep disorders are assumed to be caused by a mismatch between the individual circadian phase position and the desired sleep-wake schedule. Benzodiazepines and non-benzodiazepine positive allosteric GABAA receptor modulators improve sleep onset and maintenance in the short-term treatment of insomnia. However, tolerance and dependence are important side effects. Sedating antidepressants are frequently prescribed for insomnia, however, only few randomised controlled trials have been published so far. Melatonin and melatonin receptor agonists are considered to be an option for the treatment of insomnia especially because of their minimal abuse potential and safety. First data on orexin (aka hypocretin) receptor antagonists are promising, however, the risk-benefit ratio needs to be further evaluated. With respect to circadian rhythm sleep disorders, there is solid evidence from meta-analyses supporting the use of melatonin in jet lag disorder to accelerate entrainment to the new time zone, and in delayed sleep phase disorder to advance sleep-wake rhythms. In addition to that, there is evidence supporting the use of melatonin in patients with shift work disorder in order to promote daytime sleep after night shifts.

Zolpidem-Induced Narcolepsy, Faint, Seizure or Coma? A Case Report

Zolpidem, as an imidazopyridine agent, is a widely prescribed drug among practitioners for short-term treatment of insomnia. Nevertheless, there have been a number of cases associated with the adverse effects of the stated drug recently. Many cases of serious complications induced by high dose of zolpidem have been reported. Further to the existing reports of adverse reactions to zolpidem, throughout the current manuscript, another case of zolpidem-induced loss of consciousness is going to be presented. The case had taken 100 mg of zolpidem and afterwards, went into an unknown status of narcolepsy, faint, seizure or transient coma. Overdosing zolpidem and being affected by its central effects, he performed risky actions such as cooking by a gas oven and eating meal while intoxicated. The current case suggests that zolpidem overdose might contribute to loss of consciousness and exhibition of high-risk behaviors.

Zopiclone use with Depressed Patients

Submit Manuscript | http://medcraveonline.com of combinations of antidepressants for the treatment of major depressive disorder. A missing consideration in combined medication regimens for treating depressed patients is the concurrent use of hypnotics. Zopiclone is a non-benzodiazepine hypnotic agent introduced as an alternative to benzodiazepines in 1986. Since then, accumulated empirical evidence has indicated that the drug has all the properties of benzodiazepines including adverse behavioral effects. This conclusion that zopiclone is a benzodiazepine clone is now biochemically logical as the drug binds at the benzodiazepine GABA sites as a full agonist. It is the most widely prescribed sedative hypnotic prescribed in Canada. Long term reviews of its clinical use in promoting sleep conclude that “zopiclone is effective, well-tolerated and an excellent alternative to benzodiazepines in the short term treatment of insomnia” [2]. The Canadian product monograph also emphasizes short-term treatment and that “treatment with Imovane should not usually exceed 7-10 consecutive days. Use for more than 2-3 consecutive weeks requires complete re-evaluation of the patient [3].” The link between sleep disturbances and mental disorders is clear and substantial [4]. DSM-5 encourages concurrent diagnosis of sleep disorders although this is likely still under diagnosed. The Imovane (zopiclone) monograph issues a caution for the use of the drug with depressed patients, indicates that it is not a treatment for depression and that Imovane may even mask patients’ symptoms. Yet, little information is available on what the standard of practice of using this drug with depressed patients is like. Kassam & Patten [5] described Canadian population estimates of benzodiazepine and zopiclone use in Canada and showed that patients with Major Depressive Disorder had an elevated frequency in using these agents. However, those estimates (for the previous 12 month period) are based on survey data beginning in the mid 1990’s and did show increased use of zopiclone by six years later (12.3 percent in 2000/2001). Little additional information on the practice of zopiclone use with patients who had Major Depressive Disorder is available. The files of one hundred consecutive patients (50 males; 50 females - mean age 40.1 years) referred for mental health IME’s from third-party disability insurers were reviewed, all who had a diagnosis of Major Depressive Disorder on referral (nearly all from family physicians) and whose diagnosis was confirmed through our assessment with formal objective psychological testing and clinical examination. Forty-six of these patients were taking Imovane at the time of their evaluation. As well, four more patients indicated that their use of a tricyclic antidepressant was taken in the evening to assist sleep rather than to specifically improve mood.

Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

Speed and trajectory of changes of insomnia symptoms during acute treatment with cognitive–behavioral therapy, singly and combined with medication

ObjectivesTo examine the speed and trajectory of changes in sleep/wake parameters during short-term treatment of insomnia with cognitive–behavioral therapy (CBT) alone versus CBT combined with medication; and to explore the relationship between early treatment response and post-treatment recovery status. MethodsParticipants were 160 adults with insomnia (mean age, 50.3years; 97 women, 63 men) who underwent a six-week course of CBT, singly or combined with 10mg zolpidem nightly. The main dependent variables were sleep onset latency, wake after sleep onset, total sleep time, sleep efficiency, and sleep quality, derived from sleep diaries completed daily by patients throughout the course of treatment. ResultsParticipants treated with CBT plus medication exhibited faster sleep improvements as evidenced by the first week of treatment compared to those receiving CBT alone. Optimal sleep improvement was reached on average after only one week for the combined treatment compared to two to three weeks for CBT alone. Early treatment response did not reliably predict post-treatment recovery status. ConclusionsAdding medication to CBT produces faster sleep improvement than CBT alone. However, the magnitude of early treatment response is not predictive of final response after the six-week therapy. Additional research is needed to examine mechanisms involved in this early treatment augmentation effect and its impact on long-term outcome.

Clinical study on sleep-regulating technique (TIP3–2) combined with medication of treating primary

Introduction Cognitive behavioral therapy (CBT) and hypnotic medications are efficacious for short-term treatment of insomnia, but few patients achieve complete remission with any single treatment.In patients with persistent insomnia, the addition of medication to CBT produced added benefits during acute therapy. Sleep- regulating Technique (TIP3–2) is a Symptomatic treatment method of Low Resistance Thought Induction Psychotherapy (TIP). TIP is a psychotherapy of treating insomnia or other mental disorders accompanying with insomnia.TIP is a therapy developed based on low resistance theory and thought induction theory.It combines the eastern Guidance (Dao Yin) and Qigong with western suggestion and hypnotherapy.It is supposed that this can create a low resistance background.Then to treat the patients use some psychotherapy in this condition.Sleep-regulating Technique (TIP3–2) has standard operating procedures and induction word for different symptoms of the patients. The objective of this study is to observe the curative effect of primary insomnia using Sleep-regulating Technique (TIP3–2) combined with medication. Materials and methods 70 primary insomnia patients were randomly divided into two groups, TIP combined with medication and only medication, and 35 cases Each group. The patients in medication group were given 1i«2 mg Estazolam half an hour before going to bed. On the basis of taking Estazolam, the patients in TIP combined with medication group were given Sleep-regulating Technique treatment twice a week. Observed the changes of Pittsburgh sleep quality index (PSQI) before and after treatment, and the period is 4 weeks. Results Comparison in group: In TIP combined with medication group, there are improvement in total score of PSQI, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, daytime dysfunction in statistical significance (P 0.05).In medication group, the total score of PSQI, Subjective sleep quality, sleep duration have statistical significance improvement (P 0.05); Comparison between groups: Comparing the data after treatment, There were significant differences in the total score of PSQI, subjective sleep quality, medication use and daytime dysfunction ( P 0.05 ).TIP combined with medication is better than only medication. Comparing the difference of PSQI values before and after treatment, there are significant difference between two groups in the total score of PSQI, subjective sleep quality, sleep latency, medication use and daytime dysfunction (P 0.05).TIP combined with medication is better than only medication. Conclusion The two methods have different degrees of improvement in primary insomnia.TIP combined with medication is better than only medication. It is suggested that psychological therapy combined with medication therapy is a more effective treatment of insomnia. Acknowledgements Research was funded by the following project: Prevention and treatment study of Chinese Traditional Medicine on psychological diseases:Project supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (Grant No. 2009BAI77B09). And thanks to all the members cooperation and the participants who help us accomplish the study.

Zolpidem-Related Surge in Emergency Department Visits

EMERGENCY DEPARTMENT VISITS INvolving adverse reactions to the sleep medication zolpidem increased 220% from 2005 to 2010, from 6111 visits to 19 487 visits, said the authors of a report issued May 1 by the Substance Abuse and Mental Health Services Administration (SAMHSA). Nearly 3 in 4 zolpidem-related emergency department visits involved patients aged 45 years or older, and roughly two-thirds were women. An estimated 50 million to 70 million people in the United States have chronic sleep disorders. Zolpidem, a sedative-hypnotic medicine, was approved by the Food and Drug Administration (FDA) in 1992 for the short-term treatment of insomnia and is the active ingredient in such drugs as Ambien, Ambien CR, Edluar, and Zolpimist. After the FDA initially approved zolpidem, the agency has recommended that the dose of most products containing the drug should be reduced by half when prescribed for older patients. But zolpidem is often being prescribed at the higher dose, which may increase adverse reactions, reported SAMHSA. Adverse reactions associated with zolpidem include daytime drowsiness, dizziness, hallucinations, agitation, sleepwalking, and driving while not fully awake. In addition, the drug’s sedative effects can be dangerously enhanced when the medication is combined with other substances, such as certain anti-anxiety medications and narcotic pain relievers that depress the central nervous system. In 2010, half of all emergency department visits related to zolpidem involved its use with other drugs, and 37% of all emergency department visits related to zolpidem involved additional use of drugs that depressed the central nervous system, such as antianxiety medications such as benzodiazepines, narcotic pain relievers, and alcohol, according to the SAMHSA report. “Al though s h o r t t e r m sleeping medic a t i ons can help patients, it is exceedingly important that they be carefully used and moni tored ,” sa id Pame la S. Hyde, JD, SAMHSA administrator, in a release. “Physicians and patients need to be aware of the potential adverse reactions associated with any medication and work closely together to prevent or quickly address any problems that may arise.” The findings in the SAMHSA report, “Emergency Department Visits for Adverse Reactions Involving the Insomnia MedicationZolpidem,”arebasedondata fromthe2005to2010DrugAbuseWarning Network (DAWN) reports (http: //tinyurl.com/d5shp9u).DAWNisapublichealthsurveillancesystemthatmonitors drug-related morbidity and mortality through reports from a network of hospitalsacrosstheUnitedStates.Adverse reactions are defined as emergency departmentvisitsinwhichanadversehealth consequence results when taking prescription drugs, over-the-counter medications, or dietary supplements as prescribed or recommended. news@JAMA From JAMA’s Daily News Site

Z drugs: their properties and use in treating insomnia

AbstractSteve Chaplin, Sue Wilson and Professor David Nutt provide an overview of the properties of Z drugs and how they compare in the short‐term treatment of insomnia.

Sublingual Zolpidem (Edluar™; Sublinox™)

Zolpidem is a non-benzodiazepine hypnotic used in the short-term treatment of insomnia. A sublingual orally disintegrating tablet formulation of zolpidem (Edluar™; Sublinox™) has been developed to provide a more rapid onset of action than oral immediate-release zolpidem. Sublingual zolpidem has demonstrated bioequivalence to oral zolpidem. In a randomized, double-blind, double-dummy, crossover, multi-centre study in adult patients with primary insomnia (n=70), a single 10-mg dose of sublingual zolpidem significantly reduced latency to persistent sleep (primary endpoint) compared with a single 10-mg dose of oral immediate-release zolpidem. Sleep-onset latency and latency to stage 1 sleep were also significantly shorter with sublingual zolpidem than with oral zolpidem. Moreover, compared with the oral formulation, sublingual zolpidem was noninferior in terms of total sleep time and did not significantly differ in terms of duration of wake after sleep onset. Sublingual zolpidem was generally well tolerated in this trial, with most adverse events being of mild or moderate severity. The overall tolerability profile of sublingual zolpidem was similar to that of oral zolpidem.

Two Cases of Zolpidem-Associated Homicide

Zolpidem is the most commonly prescribed medication for the short-term treatment of insomnia. Adverse reactions include nightmares, confusion, and memory deficits. Reported rare adverse neuropsychiatric reactions include sensory distortions such as hallucinations. Previous research has identified 4 factors that may place a patient at increased risk of zolpidem-associated psychotic or delirious reactions: (1) concomitant use of a selective serotonin reuptake inhibitor (SSRI), (2) female gender, (3) advanced age, and (4) zolpidem doses of 10 mg or higher. In this article, 2 cases are presented in which individuals killed their spouses and claimed total or partial amnesia. Neither individual had a history of aggressive behavior. Both had concomitantly taken 10 mg or more of zolpidem in addition to an SSRI (paroxetine).

The Incidence of Zolpidem Use in Suspected DUI Drivers in Miami-Dade Florida: A Comparative Study Using Immunalysis Zolpidem ELISA KIT and Gas Chromatography-Mass Spectrometry Screening

In 1993, Zolpidem (Ambien), a non-benzodiazepine hypnotic agent, was approved for use in the United States for the short-term treatment of insomnia. Zolpidem has a rapid onset of action and short elimination half-life, rendering it ideal as a sleep aid. The objective of this study was to evaluate, and retrospectively compare, the use of the Immunalysis ELISA kit and gas chromatograpy-mass spectrometry (GC-MS) to screen blood/urine specimens for zolpidem. In addition, results for the incidence of zolpidem in suspected DUI drivers in 2007 are compared to previous years' data. The ELISA kit was evaluated for cross-reactivity with zaleplon and zopiclone and zolpidem metabolite I. Urine samples (n = 100) and blood samples (n = 100) were selected from specimens received into the DUI laboratory in 2007 and were screened via the Immunalysis Zolpidem ELISA kit and on GC-MS in full EI scan mode following an alkaline liquid-liquid extraction. Results show 5% of the urine and blood samples screened positive for zolpidem using the ELISA kits, and all 5% confirmed positive for zolpidem using GC-MS. The ELISA kit demonstrated no cross-reactivity to zaleplon or zopiclone at a spiked urine concentration of 1000 ng/mL. Ten cases of suspected DUI drivers in 2007 confirmed positive for zolpidem by ELISA and GC-MS in blood/urine, a higher incidence rate than in the previous years. Because of the low percentage elimination of the parent compound in urine, a screening method for the detection of the main metabolite of zolpidem may be needed for better detection of drug impairment driving due to zolpidem.

Sleep Disorders More Common in Older Age

Sleep Disorders More Common in Older Age

Hypnotics Should Not be Considered for the Initial Treatment of Chronic Insomnia

Analysis of the use of hypnotic medication versus CBT for insomnia using an established model for ethical medical decision making leads to the conclusion that hypnotics are not appropriate as the initial treatment in cases of chronic insomnia. Instead, CBT should be considered as the initial treatment for chronic insomnia. This decision is based on empirical data demonstrating that CBT is equally effective in the short-term treatment of insomnia and is superior to pharmacologic treatment in the long-term management of insomnia. Long-term management is a critically important concern, since 'chronic' insomnia requires a long-term solution. Using CBT as the initial treatment is also supported by empirical data showing that combining hypnotic use with CBT leads to worse outcomes compared with CBT alone. In addition to the efficacy data described above, patients have been shown to prefer nondrug therapy for insomnia when given the choice. QoL issues support the use of CBT because of the avoidance of side effects associated with use of hypnotic medication, such as residual sedation, psychomotor and cognitive impairment, and perhaps, most importantly, psychologic dependence. The greatest challenge to endorsement of use of CBT arises from contextual issues, such as the out-of-pocket cost to the patient and availability of the treatment. In some instances, these factors may be significant barriers to the use of CBT for insomnia. These barriers can be addressed with improved insurance reimbursement for CBT, in addition to training more providers.

Zolpidem : Forensic aspects for the toxicologist and pathologist.

Zolpidem (Ambien), a nonbenzodiazepine hypnotic, is indicated for the short-term treatment of insomnia. Because it has become the most widely prescribed sleep aid in the United States, it is being increasingly detected in a variety of forensic specimens, and its interaction with other medications is being questioned. We present a comprehensive overview of the basic chemistry, pharmacokinetics, and pharmacodynamics of zolpidem; its interaction with other prescription drugs; its effects on driving and motor skills; and its analysis and interpretation in forensic casework.

The safety and tolerability of zolpidem--an update.

Zolpidem belongs to a new class of hypnotic agents, chemically distinct from the pre-existing ones, and has a unique neuropharmacological profile. It induces sedative/hypnotic effects in rodents at doses much lower than those for anticonvulsant and myorelaxant activities. Clinically, zolpidem is indicated for the short term treatment of insomnia. It has a short half-life (2.4h), with no active metabolite, and does not accumulate during repeated administration. The pharmacokinetic profile associated with the absence of active metabolites is consistent with the short duration of action and absence of residual effects that have been observed. Polysomnographic experience indicates that zolpidem induces a sleep pattern which is similar to that of physiological sleep, and which produces either no or only minimal effects on sleep architecture after abrupt discontinuation. Aspects of the general safety of zolpidem have been studied in data obtained from healthy volunteers and patients, both adult and elderly, during its clinical development and in post-marketing experience. Zolpidem appears to be well-tolerated in adults and in the elderly, when administered in accordance with prescribing instructions. The available data indicate that, in these circumstances, the risk of abuse or dependence is minimal.

Physical dependence on zopiclone: case reports

Over the past few decades there has been a reluctance to prescribe benzodiazepines for insomnia and anxiety, as evidence for dependence and withdrawal has accumulated. Alternative treatments have therefore been...