Added: Teairra Shiffer - Date: 30.06.2021 02:14 - Views: 31754 - Clicks: 8168
Background and purpose: The aim of this study was to systematically review the efficacy and tolerability of gabapentin in the treatment of sleep disturbance in patients with medical illness. Methods: PubMed was searched for randomized, double-blinded, placebo-controlled trials that reported sleep changes during gabapentin treatment up to November Findings: This review included 26 studies involving 4, participants. Implications: This study is the first to systematically assess the clinical value of gabapentin for the treatment of sleep disorders.
We found that regardless the type of sleep outcomes, gabapentin displayed stable treatment efficacy for sleep disturbance in patients with medical illness. We recommend that further studies confirm these findings in patients with primary sleep disorders.
Gabapentin, an aphadelta voltage-gated calcium channel ligand 8 that is widely used for the treatment of epilepsy, neuropathic pain, and restless legs syndrome, can enhance slow-wave sleep in both normal individuals 9 and epileptic patients 1011 and can improve slow-wave sleep and sleep efficiency and reduce nighttime awakening in patients with primary sleep disorders However, these findings have not been verified with randomized controlled trials.
Clinical studies have revealed that gabapentin could improve the objective and subjective outcomes of sleep disturbance in patient with medical illness 13 — Gabapentin Enacarbil GEn or XP is a prodrug of gabapentin, used as an Gabapentin for insomnia dosage and for pain relief in postherpetic neuralgia. This new Gabapentin for insomnia dosage of gabapentin was deed for increased oral bioavailability over gabapentin. It provides reliable drug absorption and consistent bioavailability Nevertheless, the derived from these studies had certain inconsistencies and did not undergo any systematical evaluation.
Through a systematic review of the use of gabapentin to treat restless legs syndrome, neuropathic pain, alcohol dependence, hot flashes in menopause, fibromyalgia, phantom limb pain, human immunodeficiency virus HIV -associated sensory neuropathies, and bipolar disorder, this study attempted to evaluate the efficacy and tolerability of gabapentin for the treatment of sleep disturbance in patients with medical illness.
There are no ethical issues involved in our study because our data were based on published studies. PubMed was searched for all clinical trials related to the present research topic up to November 8, In addition, we screened the reference lists of all included trials to identify additional eligible studies.
Detailed information regarding the search terms used in the literature search is provided in the Supplementary Material. Using a unified form, Gabapentin for insomnia dosage investigators independently extracted the data and created the data spreheet, which were then cross-checked to ensure data accuracy.
Disagreements were resolved by consensus. The extracted data mainly included the six composite endpoints and treatment discontinuation or drug withdrawal events that were possibly or probably related to the study drugs. Because of the diversity of outcomes reported in the included trials, only a limited of trials provided data that could be pooled for each meta-analysis.
Based on the treatment outcomes and relevant data provided by the original trials, seven composite endpoints were analyzed for evaluation. Composite Endpoints 1—6 were used to evaluate the efficacy of gabapentin, and Composite Endpoint 7 was used to evaluate treatment discontinuation or drug withdrawal events that were possibly or probably associated with gabapentin. Composite Endpoints 1—4 indicated sleep improvement after treatment. Specifically, Composite Endpoint 1 represented the net increase in the evaluation indices provided in the trials in which the Gabapentin for insomnia dosage values increased, but the baseline values were not provided.
Composite Endpoint 2 represented the net decrease of evaluation indices provided in the trials in which the index values decreased but the baseline values were not provided. Composite Endpoint 3 and Composite Endpoint 4 represented the posttreatment values of the evaluation indices provided in the trials Gabapentin for insomnia dosage which the index values increased and the trials in which the index values decreased none of these trials provided the baseline valuesrespectively. Composite Endpoint 5 Excellent, 0 or Good represented the sleep outcomes that received the highest grades in the survey, e.
Based on the GRADE study group criteria 20we graded the evidence quality for all of the endpoints. Based on the formula and endpoint definition, the values of the same endpoints in each trial were pooled first and then the data from different trials were pooled together for analysis.
The standardized mean difference SMD and risk ratio RR were used to assess the abovementioned endpoints. Prior to the meta-analysis of each endpoint, statistical heterogeneity across the various trials was tested using Chi-square test.
A P -value greater than the nominal level of 0. The inverse variance method was used for continuous variables, and the Mantel—Haenszel method was used for dichotomous variables. In addition, a sensitivity analysis was conducted by removing each trial one at a time, and the publication bias was evaluated using the Egger test. Ninety-eight records were identified through database searches and were screened by reading titles, abstracts, and part of main text.
After irrelevant papers, observational studies, duplicates, and trials that used non-placebo control drugs were excluded, 26 papers 13 — 1921 — 374041 met the inclusion criteria. The included publications comprised eight RLS-related trials, eight neuropathic pain-related trials, and three alcohol dependence-related trials, two trials involving hot flashes in menopause, one fibromyalgia-related trial, one trial involving phantom limb pain, one trial involving HIV-associated sensory neuropathies, and one bipolar disorder-related trial.
Among the included studies, six trials were included only for systematic review and 20 trials were included for meta-analysis. The included 26 trials involved 4, patients. The average follow-up length was The average age of Among Figure 1 presents the screening process used in the study, Table 1 lists the main characteristics of all included trials.
There were seven trials 141618193233 Gabapentin for insomnia dosage, 41 Except for the 26 trials above that had unclear risks, the trials included in this study had low risks of bias Figures S1 and S2 in Supplementary Material. A pooled analysis of eight trials 212325 — 27294041 demonstrated that other than some indicators in three trials 26 Gabapentin for insomnia dosage, 4041gabapentin showed a treatment efficacy superior to that of the placebos in all trials Table 2.
Figure 2. Except for Composite Endpoint 3, the treatment effects of gabapentin were superior to those of the placebo; a random-effects model. Figure 3. The treatment effects of gabapentin were superior to those of the placebo; the tolerability of gabapentin was lower than that of the placebo; a random-effects model. All of the trials reported mild-to-moderate adverse effects. The moderate adverse effects occurred primarily during the dose-increasing phase and ificantly decreased in frequency afterward.
Drowsiness, dizziness, and weakness were the most frequently reported effects. These discomforts were tolerable for the majority of patients but resulted in drug withdrawal in a portion of patients. A meta-analysis of 20 trials 714 — 1719212225 — 2832 — 37 showed that for adverse events that were possibly or probably related to the study drug and could lead to treatment discontinuation and drug withdrawal, the gabapentin group had a 1.
Sixteen trials 141719212225 — 2931 — 3436 reported serious adverse effects. However, other than one case of headache 34one case of serious dizziness and drowsiness 21and one case of vision disturbance 19no serious adverse effects were associated with the use of gabapentin. No serious adverse events associated with the use of placebos were found.
For the GRADE classifications of evidence quality, the high, moderate, low, and extremely low were 0, 3, 3, and 0, respectively Table 3. The sensitivity analysis indicated that, for Composite Endpoint 1, the removal of any one trial led to a lower limit of the CI of SMD that was higher than 0; for Composite Endpoint 2 and Composite Endpoint 4, the removal of any one trial led to an upper limit of the CI of SMD that was lower than 0; for Composite Endpoint 5 and Composite Endpoint 7, the removal of any one trial led to a lower limit of the CI of the RR that was higher than 1; for Composite Endpoint 6, the removal of any one trial led to the lower limit of the CI of the RR that was lower than 1 Figures S3—S8 in Supplementary Material.
The above suggest that the for these endpoints were robust and had a low sensitivity. The P Gabapentin for insomnia dosage of all endpoints derived from the Egger test were greater than 0. This study revealed that without consideration of the type of sleep outcomes, gabapentin was ificantly superior to placebos for the treatment for sleep disorders secondary to RLS, neuropathic pain, alcohol dependence, hot flashes in menopause, fibromyalgia, phantom limb pain, HIV-associated sensory neuropathies, and bipolar Gabapentin for insomnia dosage.
The above conclusion was drawn from an extensive summary of trials involving various primary diseases. Only a small portion of these trials reported the baseline sleep status 1418212627363741and none of these trials Gabapentin for insomnia dosage the sleep status prior to the disease. Because it was impossible to distinguish absolutely true, partially true, and false sleep disturbance, we could not exclude the contribution of false sleep disturbance to the final treatment efficacy in patients with medical illness. In terms of the psychological aspects of insomnia, the intention to fall sleep often becomes a driving factor of sleep difficulty 47 and worries about being sleepless often cause early awakening or anxiety 48particularly among patients who are prone to excessive worry or over thinking.
Without timely correction, one episode of sleep difficulty can easily induce a second episode in patients with related psychological traits, and as a result, ongoing sleep difficulties ultimately lead to a chronic sleep disorder. Some researchers believe that the initiating event does not ificantly affect the progression of chronic sleep disorders 49 and that chronic sleep disorders are not closely associated with primary disease and thus do not improve with the improvement of the primary disease. In other words, during the chronic course of the abovementioned primary diseases, false sleep disturbance might have transformed into true or partially true sleep disturbance in patients with medical illness for the majority of the sample pool.
Thus, we believe the existence of false sleep disturbance in medical illness would not ificantly affect the of the efficacy analysis, and the improvement of sleep disorders can be attributed to the efficacy of gabapentin treatment. The following experimental Gabapentin for insomnia dosage supports this deduction: gabapentin can shorten sleep latency 36reduce awakenings 12263536reduce fast-wave sleep 23enhance slow-wave Gabapentin for insomnia dosage 9 — 121836prolong the total sleep time 182336increase sleep efficiency 121836and improve the quality of sleep 172335 In fact, because of its sedative effect in various diseases, gabapentin has been clinically used as a hypnotic Nevertheless, its efficacy for primary sleep disorders remains to be verified by randomized controlled trials, and the optimal dosage that is effective and tolerable in most patients needs to be identified.
It is necessary to emphasize that despite its inificant impact on the progression of sleep disorders, the initial sleep difficulty can induce the recurrence of disease In other words, the complete cure of sleep disorders requires a complete removal of the initiating stimulus.
Moreover, it is worth noting that pooled statistics were used with the basic premise of analyzing the efficacy of gabapentin. In a broad sense, this research method is in accordance with the basic principle of meta-analysis Through a systematic review and meta-analysis, this study for the first time systematically evaluated the clinical value of gabapentin for the treatment of sleep disorders. Used as a starting point, this study could inspire more researchers to conduct in-depth research on this topic. Because of the difficulty of distinguishing false sleep disturbance from true ones in patients with medical illness, we were unable to exclude their contribution to the treatment efficacy.
In addition, because of the limitations of the original trials, we were unable to conduct a meta-analysis of individual sleep outcomes and analyses related to treatment dose and timing or patient gender. This is the first study to systematically evaluate Gabapentin for insomnia dosage clinical value of gabapentin for the treatment of sleep disorders. Because the adverse events often occurred during the dose-increasing phase, and the dose was high, reducing the dose-increasing speed and lowering the dosage of gabapentin might reduce the risk. In addition, it would be ideal if our conclusions could be further verified in patients with primary sleep disorders.
We greatly appreciate the help of Dr. Role of the Funding Source : The research and conclusions were not affected by the financial support.
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