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PLoS Medicine Dec 2019There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes.
METHODS AND FINDINGS
CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case-control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only.
CONCLUSIONS
Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.
Topics: Case-Control Studies; Eclampsia; Female; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Parturition; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Prospective Studies
PubMed: 31809499
DOI: 10.1371/journal.pmed.1002988 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures.... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures. Pharmacological treatment remains the first choice to control epilepsy. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we have presented a summary of evidence for the use of STM as monotherapy in epilepsy.
OBJECTIVES
To assess the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug for people with epilepsy.
SEARCH METHODS
We searched the following databases on 13 April 2020: the Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 10 April 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: treatment withdrawal; seizure-free at six months; adverse effects; and quality of life scoring. We conducted the primary analyses by intention-to-treat where possible, and presented a narrative analysis of the data.
MAIN RESULTS
We included four studies involving a total of 355 participants: three studies (209 participants) with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS), and one study (146 participants) with a diagnosis of generalised tonic-clonic seizures (GTCS). STM was given as monotherapy compared with placebo and with levetiracetam in the BECTS studies, and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. For the primary outcome, the total number of dropouts caused either by seizure recurrence or adverse reaction was significantly higher in the levetiracetam treatment arm compared to the STM treatment arm (RR 0.32, 95% Cl 0.10 to 1.03; 1 study, 43 participants; low-certainty evidence). For the secondary outcomes for this comparison, results for seizure freedom were inconclusive (RR 1.12, 95% Cl 0.88 to 1.44; 1 study, 43 participants; low-certainty evidence). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than participants receiving phenytoin in the GTCS study (RR 0.03, 95% CI 0.00 to 0.58; 1 study, 146 participants; low-certainty evidence). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. The most common adverse events were related to behavioural disturbances when STM was compared with levetiracetam (RR 0.95, 95% Cl 0.59 to 1.55; 1 study, 43 participants; low-certainty evidence), with the same incidence in both groups. No data were reported for quality of life. Overall, we assessed one study at high risk of bias and one study at unclear bias across the seven domains, mainly due to lack of information regarding study design. Only one trial reported effective methods for blinding. The risk of bias assessments for the other two studies ranged from low to high. We rated the overall certainty of the evidence for the outcomes as low using the GRADE approach.
AUTHORS' CONCLUSIONS
This review provides insufficient information to inform clinical practice. Small sample sizes, poor methodological quality, and lack of data on important outcome measures precluded any meaningful conclusions regarding the efficacy and tolerability of sulthiame as monotherapy in epilepsy. More trials, recruiting larger populations, over longer periods, are needed to determine whether sulthiame has a clinical use.
Topics: Anticonvulsants; Epilepsy; Humans; Quality of Life; Randomized Controlled Trials as Topic; Thiazines
PubMed: 34554571
DOI: 10.1002/14651858.CD010062.pub3 -
The Cochrane Database of Systematic... Jul 2022This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator.
OBJECTIVES
To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy.
SEARCH METHODS
For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform.
SELECTION CRITERIA
We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood
MAIN RESULTS
We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes.
AUTHORS' CONCLUSIONS
VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.
Topics: Adult; Anticonvulsants; Child; Cough; Drug Resistant Epilepsy; Drug Therapy, Combination; Dyspnea; Hoarseness; Humans; Pain; Paresthesia; Seizures; Vagus Nerve Stimulation
PubMed: 35833911
DOI: 10.1002/14651858.CD002896.pub3 -
The Journal of Headache and Pain Dec 2023Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence.
AIM
To assess the cost-effectiveness of drugs used to treat adults with chronic migraine.
METHODS
We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes.
RESULTS
Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY.
CONCLUSIONS
Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.
Topics: Adult; Humans; Topiramate; Migraine Disorders; Headache; Cost-Benefit Analysis; Decision Making; Quality-Adjusted Life Years
PubMed: 38053051
DOI: 10.1186/s10194-023-01686-y -
Developmental Medicine and Child... Nov 2022We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat... (Meta-Analysis)
Meta-Analysis Review
AIM
We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms.
METHOD
All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed.
RESULTS
Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO combination, high dose ACTH (with/without vitamin B ), high dose prednisolone, and low dose ACTH were 'best'.
INTERPRETATION
Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms.
WHAT THIS PAPER ADDS
Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Child; Humans; Infant; Magnesium Sulfate; Methylprednisolone; Network Meta-Analysis; Spasms, Infantile; Treatment Outcome; Vitamins
PubMed: 35765990
DOI: 10.1111/dmcn.15330 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses. Catamenial epilepsy and seizure exacerbation is common in women with epilepsy. Women may not receive appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aims to address these issues to inform clinical practice and future research.
OBJECTIVES
To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included RCTs and quasi-RCTs of blinded or open-label design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. We included the following types of interventions: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.
DATA COLLECTION AND ANALYSIS
We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.
MAIN RESULTS
Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone, and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses. Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group. The results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I = 0%). No treatment withdrawals were reported from the norethisterone RCTs. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life. We judged the evidence for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.
AUTHORS' CONCLUSIONS
This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out. Our review highlights an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those women who do not have regular menses. Further clinical trials are needed in this area.
Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Fatigue; Female; Humans; Menstruation; Middle Aged; Randomized Controlled Trials as Topic; Seizures; Young Adult
PubMed: 34528245
DOI: 10.1002/14651858.CD013225.pub3 -
Therapeutics and Clinical Risk... 2023Levothyroxine is a common prescribed drug. Many medications and food, however, can interfere with its bioavailability. The aim of this review was to summarize the... (Review)
Review
PURPOSE
Levothyroxine is a common prescribed drug. Many medications and food, however, can interfere with its bioavailability. The aim of this review was to summarize the medications, food and beverages that interact with levothyroxine and to assess their effects, mechanisms and treatments.
METHODS
A systematic review on interfering substances that interact with levothyroxine was performed. Web of Science, Embase, PubMed, the Cochrane library, grey literature from other sources and the lists of references were searched for human studies comparing the levothyroxine efficacy with and without interfering substances. The patient characteristics, drug classes, effects and mechanism were extracted. The NHLBI study quality assessment tools and the JBI critical appraisal checklist were used to assess the quality of included studies.
RESULTS
A total of 107 articles with 128 studies were included. Drugs interactions were revealed in calcium and iron supplements, proton pump inhibitors, bile acid sequestrants, phosphate binders, sex hormones, anticonvulsants and other drugs. Some food and beverage could also induce malabsorption. Proposed mechanisms included direct complexing, alkalization, alteration of serum thyroxine-binding globulin levels and acceleration of levothyroxine catabolism via deiodination. Dose adjustment, administration separation and discontinuation of interfering substances can eliminate the interactions. Liquid solutions and soft-gel capsules could eliminate the malabsorption due to chelation and alkalization. The qualities of most included studies were moderate.
CONCLUSION
Lots of medications and food can impair the bioavailability of levothyroxine. Clinicians, patients and pharmaceutical companies should be aware of the possible interactions. Further well-designed studies are needed to provide more solid evidence on treatment and mechanisms.
PubMed: 37384019
DOI: 10.2147/TCRM.S414460 -
Cells Feb 2022Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been... (Review)
Review
BACKGROUND AND OBJECTIVES
Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented.
MATERIALS AND METHODS
PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied.
RESULTS
Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms.
CONCLUSIONS
The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine's side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine-lamotrigine combination in bipolar patients.
Topics: Animals; Antidepressive Agents; Depression; Humans; Ketamine; Lamotrigine; Psychopharmacology
PubMed: 35203296
DOI: 10.3390/cells11040645 -
JAMA Network Open Aug 2023Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.
OBJECTIVE
To evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.
DATA SOURCES
PubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.
STUDY SELECTION
Randomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently performed data extraction following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.
RESULTS
Twenty-seven randomized clinical trials with 1861 patients (median age, 45.99 years [range, 20.00-70.00 years]; 759 women [40.8%]) were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of -22.07% (95% CI, -33.22% to -10.92%) for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events (nausea, vomiting, and dizziness) among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.
CONCLUSIONS AND RELEVANCE
These findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments.
Topics: Humans; Female; Middle Aged; Gabapentin; Pregabalin; Analgesics; Analgesics, Opioid; Network Meta-Analysis; Pain, Postoperative
PubMed: 37556139
DOI: 10.1001/jamanetworkopen.2023.28121 -
Arquivos de Neuro-psiquiatria Jun 2023Chronic low back pain (CLBP) is a global health problem, and gabapentin and pregabalin are often used in the treatment of patients without associated radiculopathy or...
BACKGROUND
Chronic low back pain (CLBP) is a global health problem, and gabapentin and pregabalin are often used in the treatment of patients without associated radiculopathy or neuropathy. Therefore, determining their efficacy and safety is of enormous value.
OBJECTIVE
To examine the efficacy and safety of using gabapentin and pregabalin for CLBP without radiculopathy or neuropathy.
METHODS
We performed a search on the CENTRAL, MEDLINE, EMBASE, LILACS, and Web of Science data bases for clinical trials, cohorts, and case-control studies that evaluated patients with CLBP without radiculopathy or neuropathy for at least eight weeks. The data were extracted and inserted into a previously-prepared Microsoft Excel spreadsheet; the outcomes were evaluated using the Cochrane RoB 2 tool, and the quality of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
RESULTS
Of the 2,230 articles identified, only 5 were included, totaling 242 participants. In them, pregabalin was slightly less efficacious than amitriptyline, the combination of tramadol/acetaminophen, and celecoxib, and pregabalin added to celecoxib showed no benefit when compared to celecoxib alone (very low evidence for all). On the other hand, although one study with gabapentin did not support its use in a general sample of patients with low back pain, another found a reduction in the pain scale and improved mobility (moderate evidence). No serious adverse events were observed in any of the studies.
CONCLUSION
Quality information to support the use of pregabalin or gabapentin in the treatment of CLBP without radiculopathy or neuropathy is lacking, although results may suggest gabapentin as a viable option. More data is needed to fill this current gap in knowledge.
Topics: Humans; Radiculopathy; Gabapentin; Pregabalin; Low Back Pain; Celecoxib
PubMed: 37379868
DOI: 10.1055/s-0043-1764414