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Journal of Studies on Alcohol and Drugs Jul 2022This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
OBJECTIVE
This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
METHOD
We conducted a PRISMA (Preferred Reporting Items for Systematic Revision and Meta-Analyses)-guided scoping review of the published PAWS literature, searching six electronic databases (from their inception through December 2020) for English-language randomized and nonrandomized studies.
RESULTS
A total of 16 treatment studies met the inclusion criteria. The strength of evidence overall for pharmacologic treatments is low, with often only short-term results being reported, small treatment samples used, or inconsistent results found. However, for negative affect and sleep symptoms, more evidence supports using gabapentinoids (gabapentin and pregabalin) and anticonvulsants (carbamazepine and oxcarbazepine). Although preliminary data support acamprosate, there were no controlled trials. Despite an older treatment trial showing some positive data for amitriptyline for mood, the clinical measures used were problematic, and side effects and safety profile limit its utility. Finally, there is no evidence that melatonin and other agents (homatropine, Proproten-100) show PAWS symptoms.
CONCLUSIONS
Although there is some evidence for targeted pharmacotherapy for treating specific PAWS symptoms, there are few recent, robust, placebo-controlled trials, and the level of evidence for treatment efficacy is low.
Topics: Alcoholism; Anticonvulsants; Benzodiazepines; Gabapentin; Humans; Substance Withdrawal Syndrome
PubMed: 35838423
DOI: 10.15288/jsad.2022.83.470 -
Spinal Cord Series and Cases Jul 2022Systematic review.
STUDY DESIGN
Systematic review.
OBJECTIVES
This systematic review evaluates all randomized clinical trials (RCTs) conducted on assessing the efficacy and safety of pharmacologic therapies for the treatment of Spinal Cord Injury (SCI)-associated pain.
METHODS
The PubMed/Medline, EMBASE, and Cochrane library online databases were searched from 1946 to May 2019 using specific search terms for SCI, pain, and RCTs meeting predetermined inclusion criteria. The efficacy outcome of interest was pain reduction, discontinuations, and adverse events (AEs).
RESULTS
Of 2746 records identified through database searching, 703 duplicates were deleted. 1814 were excluded, the full text of the remaining 230 articles was reviewed, and finally, 28 papers were selected for drafting. The most studied medications were pregabalin, gabapentin, amitriptyline, and ketamine. Pregabalin, gabapentin, and amitriptyline reduced VAS by more than 30%, and ketamine reduced VAS by 40%. Oxcarbazepine, lamotrigine, alfentanil, tramadol, and morphine added to clonidine, baclofen, and botulinum toxin type A (BTA) significantly reduced pain compared with placebo. On the other hand, valproate, levetiracetam, trazodone, and duloxetine did not significantly alleviate SCI-associated pain compared to placebo. The risks of AEs and discontinuations in anticonvulsants were the least, while it was highest in analgesics.
CONCLUSIONS
Studies of SCI-associated pain were few, small, heterogenic in measures and values, and did not allow quantitative comparisons of efficacy. However, available data suggested pregabalin and gabapentin led to a more marked reduction in SCI-associated pain with fewer AEs. Additional clinical studies are needed to assess the effect of established and novel management options.
Topics: Amitriptyline; Anticonvulsants; Gabapentin; Humans; Ketamine; Pain; Pregabalin; Spinal Cord Injuries
PubMed: 35788127
DOI: 10.1038/s41394-022-00529-3 -
Pharmaceutics Jun 2022This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used... (Review)
Review
BACKGROUND
This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment.
METHODS
A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021.
RESULTS
Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication-gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/; (2) celecoxib/; (3) piroxicam/, ; (4) diclofenac/, , , ; (5) meloxicam/; (6) aspirin/, , and ; (7) amitriptyline/ and ; (8) imipramine/; (9) nortriptyline/, , ; and (10) escitalopram/, , and .
CONCLUSIONS
Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management.
PubMed: 35745763
DOI: 10.3390/pharmaceutics14061190 -
Frontiers in Neurology 2022Medical cannabis (MC) has been hypothesized as an alternative therapy for migraines, given the undesirable side effects of current migraine medications. The objective of...
BACKGROUND
Medical cannabis (MC) has been hypothesized as an alternative therapy for migraines, given the undesirable side effects of current migraine medications. The objective of this review was to assess the effectiveness and safety of MC in the treatment of migraine in adults.
METHODS
We searched PubMed, EMBASE, PsycINFO, CINAHL, and Web of Science for eligible studies in adults aged 18 years and older. Two reviewers independently screened studies for eligibility. A narrative synthesis of the included studies was conducted.
RESULTS
A total of 12 publications involving 1,980 participants in Italy and the United States of America were included.Medical cannabis significantly reduced nausea and vomiting associated with migraine attacks after 6 months of use. Also, MC reduced the number of days of migraine after 30 days, and the frequency of migraine headaches per month. MC was 51% more effective in reducing migraines than non-cannabis products. Compared to amitriptyline, MC aborted migraine headaches in some (11.6%) users and reduced migraine frequency. While the use of MC for migraines was associated with the occurrence of medication overuse headaches (MOH), and the adverse events were mostly mild and occurred in 43.75% of patients who used oral cannabinoid preparations.
CONCLUSIONS
There is promising evidence that MC may have a beneficial effect on the onset and duration of migraine headaches in adults. However, well-designed experimental studies that assess MC's effectiveness and safety for treating migraine in adults are needed to support this hypothesis.
PubMed: 35711271
DOI: 10.3389/fneur.2022.871187 -
JAMA Network Open May 2022Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia.
OBJECTIVE
To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.
DATA SOURCES
Searches of PubMed/MEDLINE, Cochrane Library, Embase, and Clinicaltrials.gov were conducted on November 20, 2018, and updated on July 29, 2020.
STUDY SELECTION
Randomized clinical trials (RCTs) comparing amitriptyline or any FDA-approved doses of investigated drugs.
DATA EXTRACTION AND SYNTHESIS
This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Four independent reviewers extracted data using a standardized data extraction sheet and assessed quality of RCTs. A random-effects bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021.
MAIN OUTCOMES AND MEASURES
Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Relative treatment ranking using the surface under the cumulative ranking curve (SUCRA) was also evaluated.
RESULTS
A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, -0.97; 95% CrI, -1.10 to -0.83), fatigue (SMD, -0.64; 95% CrI, -0.75 to -0.53), and improved quality of life (SMD, -0.80; 95% CrI, -0.94 to -0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, -0.33; 95% CrI, -0.36 to -0.30) and depression (SMD, -0.25; 95% CrI, -0.32 to -0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.
CONCLUSIONS AND RELEVANCE
These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.
Topics: Amitriptyline; Duloxetine Hydrochloride; Fatigue; Female; Fibromyalgia; Humans; Male; Middle Aged; Milnacipran; Network Meta-Analysis; Pain; Pregabalin; United States; United States Food and Drug Administration
PubMed: 35587348
DOI: 10.1001/jamanetworkopen.2022.12939 -
Frontiers in Neurology 2022To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network...
Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.
OBJECTIVE
To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network analysis.
METHODS
A Bayesian network meta-analysis of literature searches within PubMed, Cochrane Library, Embase, and Web of Science databases from their inception to February 21 2021 was conducted without language restrictions. Paired and network meta-analyses of random effects were used to estimate the total standardized mean deviations (SMDs) and odds ratios (ORs).
RESULTS
A total of 1,133 citations were identified and 20 RCTs (including 1,198 patients) involving 11 drugs and placebos for post-SCI NP selected. The 5 outcomes from all 11 drugs and placebos had no inconsistencies after Bayesian network analysis. BTX-A gave the most effective pain relief for the 4 weeks, following a primary outcome. No significant differences were found among drugs with regard to adverse events of the primary outcome. Gabapentin, BTX-A, and pregabalin were found to be the most helpful in relieving secondary outcomes of mental or sleep-related symptoms with differences in SMDs, ranging from -0.63 to -0.86. Tramadol triggered more serious adverse events than any of the other drugs with differences in ORs ranging from 0.09 to 0.11.
CONCLUSION
BTX-A, gabapentin, pregabalin, amitriptyline, ketamine, lamotrigine, and duloxetine were all effective for NP management following SCI. Lamotrigine and gabapentin caused fewer side effects and had better efficacy in relieving mental or sleep-related symptoms caused by SCI-related NP. Tramadol, levetiracetam, carbamazepine, and cannabinoids could not be recommended due to inferior safety or efficacy.
SYSTEMATIC REVIEW REGISTRATION
[https://inplasy.com/inplasy-2020-7-0061/], identifier [INPLASY202070061].
PubMed: 35386408
DOI: 10.3389/fneur.2022.818522 -
The Cochrane Database of Systematic... Mar 2022Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed... (Review)
Review
BACKGROUND
Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment.
OBJECTIVES
To assess the effects of medication for reducing PTSD symptoms in adults with PTSD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020.
SELECTION CRITERIA
All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD.
DATA COLLECTION AND ANALYSIS
Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity.
MAIN RESULTS
We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis. For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence. For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events.
AUTHORS' CONCLUSIONS
The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amitriptyline; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Humans; Middle Aged; Mirtazapine; Paroxetine; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Young Adult
PubMed: 35234292
DOI: 10.1002/14651858.CD002795.pub3 -
Frontiers in Pharmacology 2021This study assessed the efficacy, acceptability, and safety of pharmaceutical management for combat-related post-traumatic stress disorder (PTSD) to provide a clinical... (Review)
Review
Effectiveness, Acceptability and Safety of Pharmaceutical Management for Combat-Related PTSD in Adults Based on Systematic Review of Twenty-Two Randomized Controlled Trials.
This study assessed the efficacy, acceptability, and safety of pharmaceutical management for combat-related post-traumatic stress disorder (PTSD) to provide a clinical decision-making basis for clinicians. A comprehensive search was conducted using Ovid MEDLINE, Ovid EMBASE, Cochrane Library, Scopus, ScienceDirect, and Web of Science for randomized controlled trails (RCTs), which reported pharmaceutical management and placobo for adults with combat-related PTSD, that were published until April 21, 2021. The effectiveness, acceptability, and adverse events (AEs), were designed as interested outcomes. The change in total symptoms of combat-related PTSD according to the clinician rating scale was defined as primary outcome, and the others were defined as secondary outcomes. Twenty-two RCTs with 1,221 patients were involved. Compared with placebo, overall active comparators had statistical differences for all outcomes, including the change in total symptoms of combat-related PTSD [SMD = -0.36, 95%CI (-0.62,-0.09)], depression [SMD = -0.28, 95%CI (-0.45,-0.10)], anxiety [SMD = -0.44, 95%CI (-0.64,-0.23)], re-experience [SMD = -0.33, 95%CI (-0.52,-0.13)], avoidance [SMD = -0.24, 95%CI (-0.43,-0.05)], and hyper-arousal [SMD = -0.26, 95%CI (-0.48,-0.03)]. Compared with the placebo, in terms of acceptability, overall active comparators did not significantly decrease all-cause discontinuance rates [RR = 0.97, 95%CI (0.78,1.20)], and the significance decreased due to AEs [RR = 2.42, 95%CI (1.41,4.13)]. Nevertheless, overall there was no statistically significant difference for overall AEs, including somnolence, sedation, dizziness, paresthesia, anxiety, blurred vision, generalized anxiety disorder, and sleep disturbance. All funnel plots were symmetrical and no publication bias was found. Active drugs, especially amitriptyline, imipramine, and quetiapine, had a positive effect on the improvement of combat-related PTSD symptoms. Despite there being no significant increase in the AEs of the active drugs, the fact that the discontinuation rates of these drugs, including risperidone, imipramine, and topiramate, were increased deserves attention. Furthermore, as active drugs were effective across ethnic groups and battlefields, active drug regimens were revealed to be more appropriate for treating people with symptoms of extreme severe PTSD (≥80) or PTSD that is at least 8 weeks old. In addition, current evidence was from adults under 60 years of age and male combat-related PTSD. Whether this evidence can be extended to other populations of combat-related PTSD needs to be confirmed by subsequent high-quality, large-sample studies.
PubMed: 35115944
DOI: 10.3389/fphar.2021.805354 -
CNS Spectrums Jan 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.
METHODS
We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.
RESULTS
We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.
CONCLUSIONS
Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.
PubMed: 35086595
DOI: 10.1017/S1092852922000050 -
Journal of Clinical PsychopharmacologyTranylcypromine is the only irreversible monoamine oxidase inhibitor that is approved in the United States and in Europe for the management of treatment-resistant major...
BACKGROUND
Tranylcypromine is the only irreversible monoamine oxidase inhibitor that is approved in the United States and in Europe for the management of treatment-resistant major depressive disorder. Comprehensive data in the literature regarding the efficacy and tolerability of tranylcypromine (TCP) combination strategies have not been systematically investigated yet.
METHODS
We conducted a systematic review of available literature based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Study types considered eligible for inclusion were studies that reported information on efficacy and/or tolerability/adverse effects of pharmacological TCP add-on or coadministration strategies among people with psychiatric disorders.
RESULTS
Ninety-six articles were included in qualitative analyses. A relevant body of evidence shows that TCP combined with first- and second-generation antipsychotics seems relatively safe and might have beneficial effects in some patients with depressive disorders, although caution is needed with some second-generation antipsychotics that have proserotonergic activity. Although evidence is not entirely consistent, amitriptyline as add-on agent might be efficacious and associated with a low rate of severe adverse events. Although available data from case reports are scarce, certain other agents, such as trazodone, but also lithium, seem to have a good risk-benefit profile with regard to TCP that should be further investigated in the context of high-quality studies.
CONCLUSIONS
Any combination of a psychotropic with TCP should be preceded by an evaluation of drug-to-drug interaction and an informed consent process and followed by close monitoring. Before any combination strategy, doctors should reevaluate factors of pseudo-treatment resistance, such as rapid-metabolizing status, noncompliance, trauma, alternative diagnosis, or drug abuse.
Topics: Depressive Disorder, Treatment-Resistant; Drug Interactions; Drug Therapy, Combination; Humans; Mental Disorders; Monoamine Oxidase Inhibitors; Psychotropic Drugs; Tranylcypromine
PubMed: 34928561
DOI: 10.1097/JCP.0000000000001498