Pain Medicine

SR: Efficacy and Safety of Non-Pharmacological, Pharmacological, and Surgical Treatments for Hand Osteoarthritis

16 Jan, 2025 | 10:54h | UTC

Background: Hand osteoarthritis (OA) affects a substantial proportion of older adults, contributing to pain, reduced grip strength, and functional limitations. While several clinical guidelines recommend patient education, exercise, and topical or oral non-steroidal anti-inflammatory drugs (NSAIDs), the level of evidence remains varied. In 2018, a systematic review identified efficacy data from 126 studies. This updated review includes 65 new randomized controlled trials (RCTs) published through December 2023, aiming to provide the most current evidence on hand OA treatments.

Objective: To summarize and evaluate the efficacy and safety of non-pharmacological, pharmacological, and surgical interventions for hand OA, highlighting both short-term (<3 months) and long-term (≥3 months) outcomes for pain, function, and grip strength.

Methods: The authors searched PubMed/MEDLINE, Embase, and Cochrane CENTRAL for RCTs published from June 2017 to December 2023. Risk of bias was assessed using the RoB2 tool, and certainty of evidence was evaluated with GRADE criteria. Interventions included hand exercises, orthoses, assistive devices, thermal modalities, pharmacologic therapies (e.g., oral/topical NSAIDs, glucocorticoids, disease-modifying anti-rheumatic drugs), and various surgical techniques. Meta-analyses were conducted when appropriate, and outcomes were expressed as standardized mean differences or relative risks with 95% confidence intervals.

Results:

• Non-Pharmacological Interventions: Low- to moderate-certainty evidence supports hand exercises, thumb orthoses, and assistive devices for improving pain and function. Hand exercises showed a small long-term effect on pain, while thumb orthoses offered a moderate long-term effect on pain. Assistive devices demonstrated a moderate long-term benefit for function. Few mild adverse events were reported in these categories.
• Pharmacological Interventions: There is high-certainty evidence for a very small short-term functional improvement with topical NSAIDs and low-certainty evidence of moderate short-term pain relief with oral NSAIDs. Oral glucocorticoids likely yield a small, short-term functional benefit. Methotrexate showed a possible small long-term effect on pain but no clear impact on function. No new data support intra-articular steroid injections, hydroxychloroquine, or biologic DMARDs for meaningful improvements; in these trials, sponsor bias and cost considerations underscore the need for critical appraisal, given the typically higher expense of advanced agents like biologics.
• Surgical Interventions: Ten new studies compared various surgical techniques but did not include robust controls versus nonsurgical management or sham surgery. Heterogeneity precluded pooling of results, and no definitive superiority emerged for any particular procedure.

Conclusions: This systematic review reaffirms the central role of non-pharmacological interventions, especially exercise, orthoses, and assistive devices, for improving pain and function in hand OA with minimal adverse events. Pharmacological treatments offer modest short-term benefits, particularly oral NSAIDs, although cost, side-effect profiles, and real-world adherence should be considered. Surgical approaches lack high-quality comparative data, highlighting the need for well-designed trials.

Implications for Practice: Clinicians should prioritize patient education, exercises, and readily accessible interventions (e.g., orthoses, assistive devices) given their demonstrated safety and moderate efficacy. Oral or topical NSAIDs remain suitable options for acute pain management, with the understanding that longer-term use warrants caution due to possible adverse effects. In contexts where advanced pharmacologic agents (such as biologics) are evaluated, practitioners must scrutinize costs, potential sponsor influence, and marginal benefits relative to standard care.

Study Strengths and Limitations: Strengths of this review include a comprehensive literature search, systematic appraisal of risk of bias, and application of GRADE to gauge certainty. However, most RCTs were small in size or had high or unclear risk of bias, and considerable heterogeneity in study designs reduced comparability. Additional limitations include the scarcity of direct comparisons for surgical versus non-surgical approaches and inconsistent reporting of adverse events.

Future Research: High-quality, larger-scale RCTs are needed to clarify subtypes of hand OA and tailor treatments accordingly. Trials should evaluate long-term outcomes, systematically measure adverse events, and compare surgery directly with non-surgical options. Studies employing mobile health (mHealth) tools and addressing ways to enhance grip strength may further advance evidence-based hand OA management.

Reference:
Kjeken I, Bordvik DH, Osteras N, Haugen IK, Fjeldstad KAA, Skaalvik I, Kloppenburg M, Kroon FPB, Tveter AT, Smedslund G. Efficacy and safety of non-pharmacological, pharmacological and surgical treatments for hand osteoarthritis in 2024: a systematic review. RMD Open. 2024; e004963. DOI: https://doi.org/10.1136/rmdopen-2024-004963

 

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Managing Autonomic Dysfunction, Pain, and Sleep Disturbances in Parkinson’s Disease: Key Points from the German Society of Neurology Guideline

5 Jan, 2025 | 11:00h | UTC

Introduction: This text summarizes a practice-oriented 2023 guideline from the German Society of Neurology addressing non-motor manifestations of Parkinson’s disease (PD). The guideline focuses on evidence-based approaches for diagnosing and treating autonomic failure (including urogenital, cardiovascular, and gastrointestinal dysfunction), pain, and sleep disturbances—problems that often reduce quality of life and accelerate disease progression. The guideline was developed using PICO (Patient, Intervention, Comparison, Outcome) questions, comprehensive literature searches, and a consensus process among German Parkinson’s experts. By presenting stepwise recommendations, the guideline aims to help clinicians manage these non-motor aspects more effectively and improve patient outcomes.

Key Recommendations:

Autonomic Failure

• Bladder Dysfunction: Encourage behavioral modifications (e.g., timed fluid intake, bladder training) and, if necessary, consider antimuscarinics (e.g., solifenacin, trospium) or β3 agonists (e.g., mirabegron 50 mg once daily). Specifically, solifenacin 5 mg once daily, trospium 15–30 mg twice daily or darifenacin 7.5–15 mg once daily are preferred, due to their lower risk of cognitive side effects.
  • In patients who have responded inadequately to oral therapy, intravesical botulinum toxin A injection (200 U or customized) may be considered for treating severe urinary urge incontinence, if the individual motor and cognitive performance enables the subsequently likely necessary intermittent catheterization.
  • For nocturia, limit evening fluid intake and consider a 10°–20° head-up tilt in bed. In nocturnal polyuria, desmopressin (5–40 µg once daily nasal spray or 100–800 µg once daily per os) may be used with close monitoring of blood pressure, serum electrolytes and body weight.
• Orthostatic Hypotension (OH): Apply a four-step approach: (1) address aggravating factors (e.g., infections, dehydration); (2) review medications; (3) use non-pharmacological measures (increased fluid/salt intake if no contraindications, abdominal binders, head-up tilt sleeping); (4) add medications to raise blood pressure (e.g., midodrine 2.5–10 mg two to three times a day, fludrocortisone 0.1–0.3 µg once daily). For the diagnosis of OH, a Schellong test or tilt table examination should be performed.
  • Monitor for supine hypertension, which may require evening antihypertensives (e.g., low-dose losartan 25–100 mg or transdermal nitroglycerin 0.1–0.2 mg/h) and further adjustments. PD individuals with neurogenic OH should be screened for the presence of supine and nocturnal hypertension.
• Constipation: Follow the general German guideline on “Chronic Constipation.” Emphasize adequate hydration (1.5-2 L per day), fiber intake, and exercise.
  • First-line drug therapy is macrogol (polyethylene glycol, PEG, 13–26 g once daily). Consider bisacodyl (5–10 mg once daily), sodium picosulfate (5–10 mg once daily), or prucalopride (1–2 mg once daily) if needed.
• Male Erectile Dysfunction: First-line treatment involves phosphodiesterase type 5 (PDE-5) inhibitors (e.g., sildenafil 50–100 mg on demand), used cautiously in patients with orthostatic hypotension. A multidisciplinary approach with urologists is necessary.

Pain Management

• Classification: Differentiate PD-related pain (nociceptive, neuropathic, or nociplastic) from pain arising independently of PD. Use PD-specific scales, such as the King’s Parkinson’s Disease Pain Scale (KPPS) or the Parkinson’s Disease Pain Classification System (PD-PCS), to clarify pain etiology and guide therapy.
• Approach: Optimize dopaminergic therapy, especially if pain correlates with wearing-off.
  • Treat nociceptive pain per the WHO 3-step analgesic ladder (which recommends starting with non-opioid analgesics like acetaminophen or NSAIDs, then moving to mild opioids like codeine if needed, and finally to strong opioids like morphine for severe pain).
  • For neuropathic pain, preference is given to anticonvulsants (e.g., gabapentin 300–1800 mg, especially in case of concomitant restless legs syndrome) or antidepressants (e.g., duloxetine 60–120 mg, in case of concomitant depression).
  • Opioids (e.g., prolonged-release oxycodone/naloxone 5/2.5–20/10 mg, rarely up to 40/20 mg) may be considered in severe or refractory cases.

Sleep Disturbances

• Screening & Diagnosis: Use the Parkinson’s Disease Sleep Scale-2 (PDSS-2) to identify problems such as insomnia, nocturnal akinesia, restless legs, and REM sleep behavior disorder (RBD).
  • Objective tests—actigraphy, polygraphy, or video-polysomnography—are recommended for complex or treatment-refractory sleep issues.
• Treatment: Address comorbid conditions (e.g., restless legs syndrome, sleep apnea) following standard guidelines.
  • If motor fluctuations disturb sleep, adjust dopaminergic therapy (e.g., use long-acting levodopa or dopamine agonists at night).
  • RBD management typically includes creating a safe sleep environment and considering clonazepam (0.125–3 mg) or melatonin (2–9 mg).
  • Insomnia linked to circadian disruption may benefit from good sleep hygiene, bright light therapy, structured exercise, and (if indicated) low-dose agents such as eszopiclone (1 mg), doxepin (25 mg), zolpidem (5 mg), trazodone (50 mg), melatonin (2 mg), venlafaxine (37.5 mg, in case of comorbid depression), nortriptyline (25 mg) or mirtazapine (7.5 mg).
  • Excessive daytime sleepiness calls for an etiology-driven approach, with non-pharmacological strategies (e.g., scheduled naps, light therapy, exercise) and possible use of modafinil (200–400 mg) if needed. Driving should be reassessed if sleep attacks occur.

Clinical Impact: Poor sleep worsens cognitive decline, motor deficits, caregiver burden, and overall disease progression. RBD in early PD often predicts faster deterioration and earlier cognitive complications. The guideline also addresses the prognostic implications of sleep disturbances.

Conclusion: This guideline underscores the critical importance of identifying and managing non-motor symptoms in Parkinson’s disease. A structured, practice-oriented, etiology-driven stepwise approach to autonomic failure, pain, and sleep problems helps reduce the risk of dangerous complications, alleviates patient distress, and may delay the progression of both motor and cognitive domains. By integrating evidence-based recommendations into daily practice—focusing on precise assessment, tailored interventions, and regular follow-up—clinicians can improve outcomes and quality of life for individuals with PD and their caregivers.

Reference: Fanciulli A, Sixel-Döring F, Buhmann C, Krismer F, Hermann W, Winkler C, Woitalla D, Jost WH, German Parkinson’s Guideline Group, Trenkwalder C & Höglinger G (2025). Diagnosis and treatment of autonomic failure, pain and sleep disturbances in Parkinson’s disease: guideline “Parkinson’s disease” of the German Society of Neurology. Journal of Neurology (2025). DOI: https://doi.org/10.1007/s00415-024-12730-5

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Three Phase 3, Placebo-Controlled Trials Show Rapid Benefits of Oral Atogepant for Migraine Prevention

26 Dec, 2024 | 12:17h | UTC

Background: Preventive therapies for migraine often require long titration and may take weeks to achieve their full effect. This analysis integrates data from three randomized, placebo-controlled Phase 3 trials (ADVANCE, ELEVATE, PROGRESS) assessing atogepant 60 mg once daily (QD) over 12 weeks, focusing on the first four weeks. A key point is that atogepant was compared only to placebo, not to other well-established migraine preventives.

Objective: To determine whether atogepant provides early efficacy in reducing migraine frequency and improving functional outcomes within the initial weeks of therapy, for both episodic and chronic migraine.

Methods: All three studies enrolled participants aged 18–80 years with a ≥1-year history of migraine. ADVANCE and ELEVATE focused on episodic migraine (EM; 4–14 monthly migraine days), while PROGRESS studied chronic migraine (CM; ≥15 monthly headache days, ≥8 of which met migraine criteria). In ELEVATE, participants had previously failed 2–4 classes of oral migraine preventives. Throughout each trial, patients recorded daily migraine-related data and completed validated functional assessments (AIM-D and EQ-5D-5L). For this pooled analysis, only the atogepant 60 mg QD and placebo arms were examined.

Results: Atogepant recipients had a significantly lower proportion of patients with a migraine day on day 1 in all three trials, suggesting a rapid onset of benefit. Reductions in weekly migraine days (WMDs) emerged as early as week 1 and remained consistently greater than placebo over the first four weeks. Functional measures improved within this same timeframe, with patients on atogepant reporting reductions in activity impairment and enhanced self-rated health. These positive findings were observed in EM (with or without prior prophylaxis failures) and in CM populations.

Conclusions: Atogepant 60 mg QD was linked to early and significant reductions in migraine days, as well as enhancements in physical functioning and daily activities, across three placebo-controlled studies. The data suggest that atogepant may offer clinically meaningful, rapid-onset prophylactic benefits.

Implications for Practice: Clinicians may consider atogepant for patients seeking a preventive migraine therapy that demonstrates a potentially faster impact on symptom frequency and daily functioning. However, direct comparisons with established active treatments are lacking, and appropriate caution in interpreting the early onset of benefit is recommended.

Study Strengths and Limitations: Major strengths include robust, double-blind methodologies and consistent findings across diverse migraine populations. A key limitation is the exclusive use of placebo as the comparator, so the relative advantage over standard preventives remains unknown. The predominantly female and White study cohorts also restrict generalizability.

Future Research: Further investigations should evaluate atogepant in direct comparisons with existing active migraine preventives, examine long-term outcomes, and recruit more diverse populations. Such efforts could better define the therapy’s place in routine migraine care.

Reference: Lipton RB, et al. Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials. Neurology. 2025;104(2). DOI: https://doi.org/10.1212/WNL.0000000000210212

 

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Meta-analysis: Incidence Rate Difference of Adverse Events from Canabinoids in Middle-Aged and Older Adults

25 Dec, 2024 | 12:19h | UTC

Background: Growing evidence suggests that cannabinoid-based medicines (CBMs) are increasingly prescribed to individuals aged 50 years and above for various clinical conditions. While these agents may offer therapeutic benefits, questions remain about the incidence of adverse events (AEs), particularly in older adults with multiple comorbidities. This systematic review and meta-analysis aims to quantify the incidence rate difference (IRD) of AEs and determine whether weekly doses of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are associated with any dose-dependent increase in risk.

Objective: To evaluate whether adults aged ≥50 years exposed to CBMs, including THC-alone formulations and THC combined with CBD, experience a higher incidence of AEs than controls, and to assess how variations in weekly THC and CBD doses might affect AE rates.

Methods: Researchers searched MEDLINE, PubMed, EMBASE, CINAHL, PsychInfo, Cochrane Library, and ClinicalTrials.gov from January 1, 1990, to June 12, 2023. Randomized clinical trials involving middle-aged and older adults (mean age ≥50 years) using medicinal CBMs for all indications were included. Data on common and serious AEs, withdrawals, and deaths were extracted and pooled using a random-effects model. Further meta-regression analyses examined THC and CBD weekly doses as predictors of AEs in THC-only and THC:CBD trials.

Results: Fifty-eight randomized clinical trials (n=6611) met inclusion criteria, with 3450 participants receiving CBMs. Compared to controls, individuals on THC-alone experienced significantly higher incidence of dizziness, somnolence, impaired coordination, dissociative symptoms, and dry mouth, often in a dose-dependent manner. Similarly, THC:CBD combinations increased nausea, vomiting, fatigue, dizziness, and disorientation. The incidence of serious AEs, withdrawals, or mortality did not differ significantly between CBM and control groups, although neurological or psychiatric side effects were more pronounced with higher THC doses.

Conclusions: THC-containing CBMs can provoke dose-related gastrointestinal, neurological, and psychiatric adverse events, posing additional risks in older adults susceptible to falls and cognitive disturbances. However, the meta-analysis found no significant increases in serious AEs or deaths. Clinicians should weigh potential benefits against the likelihood of common side effects, especially when prescribing higher THC doses or combining cannabinoids with other medications frequently used by older patients.

Implications for Practice:

• Physicians should exercise caution when initiating or escalating THC-based therapies in middle-aged and older adults, monitoring for neurological or psychiatric AEs.
• Using lower THC doses, titrating gradually, and adding CBD may mitigate some side effects.
• Though severe AEs are uncommon, vigilance is warranted in individuals with complex medication regimens.

Study Strengths and Limitations:

• Strength: This review merges diverse clinical conditions and provides a comprehensive assessment of THC vs. THC:CBD. Its large pooled population allows for more precise IRD estimates.
• Limitation: Short treatment durations in many trials limit understanding of long-term toxicity, and some studies lacked rigorous reporting of randomization and outcome measures, potentially introducing bias.

Future Research:

• Longer-duration trials focused on older populations are needed to clarify chronic safety profiles.
• Studies exploring drug-drug interactions between CBMs and medications commonly prescribed to older adults will further elucidate real-world tolerability.

Reference: Velayudhan L, Pisani S, Dugonjic M, McGoohan K, Bhattacharyya S. Adverse events caused by cannabinoids in middle aged and older adults for all indications: a meta-analysis of incidence rate difference. Age and Ageing. 2024;53(11):afae261. DOI: https://doi.org/10.1093/ageing/afae261

 

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Bayesian Network Meta-Analysis: Chlorpromazine IV/IM Emerges as a Top Choice for Acute Migraine Relief in the ED

25 Dec, 2024 | 11:18h | UTC

Background: Acute migraine is a prevalent cause of emergency department (ED) visits, necessitating prompt pain control. Although numerous drugs are available, there is debate about the most effective and safest options. Traditional pairwise meta-analyses fail to capture all treatment comparisons in a single framework, making network meta-analyses, particularly Bayesian, an appealing approach to inform clinical decision-making.

Objective: This systematic review and Bayesian network meta-analysis aimed to compare multiple pharmacologic therapies—single agents or combinations—for acute migraine relief in adults presenting to the ED. The goal was to identify those most likely to achieve adequate pain relief, reduce rescue medication use, and minimize significant adverse reactions.

Methods: The authors searched MEDLINE, Embase, and Web of Science from inception to February 9, 2024, for randomized controlled trials comparing any pharmacologic therapy to another or to placebo in ED patients with migraine. Four primary outcomes were analyzed: (1) adequate pain relief at two hours, (2) change in pain intensity at one hour, (3) need for rescue drug at two hours, and (4) significant adverse reaction (eg, sedation, akathisia, hypotension).

Results: Twenty-four to twenty-seven trials contributed to each outcome network. Chlorpromazine IV/IM was ranked highest for adequate pain relief (SUCRA=87.3%) and also significantly reduced the need for rescue medication (SUCRA=93.2%). Ibuprofen IV and valproate IV emerged among the least effective for pain relief, while dexamethasone IV was the most probable to cause fewer serious adverse reactions (SUCRA=79.5%). However, most comparisons were of low or very low certainty, limiting the strength of the findings.

Conclusions: Chlorpromazine IV/IM appears among the most effective single agents for acute migraine in the ED, although it may carry higher risks of sedation or hypotension. Certain analgesics (eg, ibuprofen IV, valproate IV, and possibly ketorolac IV/IM) demonstrated lower efficacy. Due to variability in trial size, dosing, and participant characteristics, the overall certainty of evidence remains limited.

Implications for Practice: Clinicians may consider parenteral chlorpromazine for rapid migraine relief, balancing its adverse event profile with potential efficacy. Dexamethasone’s lower probability of serious side effects could make it a complementary option. The findings highlight the need for individualized treatment, taking into account patient comorbidities and preferences.

Study Strengths and Limitations: This network meta-analysis offers a broad comparative perspective on diverse pharmacologic interventions for ED-based migraine management. Nonetheless, there is notable heterogeneity in study methodologies, small sample sizes, and sparse direct comparisons for many interventions, all of which reduce certainty in the estimates.

Future Research: Larger, more standardized trials are needed to confirm these results and directly compare drugs like chlorpromazine, prochlorperazine, and metoclopramide-NSAID combinations. Rigorous safety reporting is crucial to clarify adverse reaction risks for various agents, especially those with less available evidence.

Reference: deSouza IS, Anthony N, Thode H Jr, et al. Effectiveness and Safety of Pharmacologic Therapies for Migraine in the Emergency Department: A Systematic Review and Bayesian Network Meta-analysis. Annals of Emergency Medicine. DOI: http://doi.org/10.1016/j.annemergmed.2024.11.004

 

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Review: Management of Degenerative Rotator-Cuff Disorders

28 Nov, 2024 | 12:48h | UTC

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RCT: Low-Dose Ketamine Enhances Pain Relief When Added to Morphine in ED Patients

20 Nov, 2024 | 14:42h | UTC

Background: Acute pain is a prevalent complaint among emergency department (ED) patients, yet effective pain management remains suboptimal, especially in individuals with current opioid use due to opioid tolerance and hyperalgesia. Low-dose ketamine (LDK) has been proposed as an adjunct to opioids to enhance analgesia through synergistic or additive effects, but its efficacy in patients with and without current opioid use in the ED setting is not well established.

Objective: This randomized controlled trial aimed to determine the effectiveness of LDK as an adjunct to morphine versus morphine alone for acute pain management in ED patients with and without current opioid use.

Methods: In this single-center, double-blind study, 116 adult patients presenting to the ED with acute pain (numeric rating scale [NRS] ≥5) requiring intravenous opioids were randomized to receive either 0.1 mg/kg ketamine or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain intensity was measured at baseline and at 10, 20, 30, 45, 60, and 120 minutes post-randomization. The primary outcome was pain reduction from baseline to 10 minutes. Secondary outcomes included pain intensity over 120 minutes, need for rescue opioids, side effects, and patient and provider satisfaction.

Results: The study included 116 patients (median age 51 years; 58% male; 36% with current opioid use). Pain reduction from baseline to 10 minutes was significantly greater in the LDK group compared to placebo (median reduction of 4 [IQR 3–6] vs. 1 [IQR 0–2]; p = 0.001). Pain intensity was significantly lower in the LDK group at 10, 20, and 30 minutes post-administration. There was a higher incidence of nausea, vomiting, and dissociation in the LDK group during the first 10 minutes. No significant differences were observed in the need for rescue opioids or in patient and provider satisfaction between groups.

Conclusions: LDK administered as an adjunct to morphine significantly enhances short-term pain relief in ED patients with acute pain, regardless of current opioid use status. However, the increased risk of transient side effects necessitates careful consideration.

Implications for Practice: LDK may be considered as an adjunct to morphine for acute pain management in the ED, particularly when traditional opioid treatments are insufficient. Clinicians should weigh the benefits against the potential for transient side effects, and LDK should not be universally recommended for all patients with moderate to severe pain.

Study Strengths and Limitations: Strengths of the study include its randomized, double-blind design and the inclusion of patients with current opioid use. Limitations include early termination leading to a smaller sample size, potentially underpowering the stratified analysis, and heterogeneity in patient pain conditions. Additionally, assessing the primary outcome at 10 minutes may not capture the peak effect of morphine.

Future Research: Further studies should focus on optimizing LDK administration protocols, such as exploring bolus versus continuous infusion methods, to achieve sustained pain reduction and minimize side effects.

Reference: Galili SF, et al. Low-dose ketamine as an adjunct to morphine: A randomized controlled trial among patients with and without current opioid use. Academic Emergency Medicine. 2024. DOI: http://doi.org/10.1111/acem.14983

 

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Meta-Analysis: Spinal Cord Stimulation May Be Effective for Chronic Back and Leg Pain

15 Nov, 2024 | 13:43h | UTC

Background: Chronic back and leg pain causes significant disability worldwide. Spinal cord stimulation (SCS) offers treatment for patients unresponsive to conventional medical management (CMM). The comparative efficacy of conventional and novel SCS forms versus CMM is debated, requiring thorough evaluation.

Objective: To evaluate the efficacy of conventional and novel SCS therapies compared with CMM in adults with chronic back or leg pain who had not previously used SCS.

Methods: A systematic review and Bayesian network meta-analysis per PRISMA guidelines were performed. MEDLINE, Embase, and Cochrane Library were searched up to September 2, 2022. Thirteen RCTs with 1,561 patients were included. Interventions were conventional SCS, novel SCS modalities (e.g., high-frequency, burst stimulation), and CMM. Primary outcomes were pain intensity (visual analog scale) and responder rates (≥50% pain relief) in back or leg. Secondary outcomes were quality of life (EQ-5D index) and functional disability (Oswestry Disability Index).

Results: At 6 months, both conventional and novel SCS were superior to CMM in five of six outcomes. For back pain responder rates, conventional SCS had an OR of 3.00 (95% CrI, 1.49–6.72) and novel SCS had an OR of 8.76 (95% CrI, 3.84–22.31) versus CMM. Pain intensity in the back decreased significantly with conventional SCS (MD, –1.17; 95% CrI, –1.64 to –0.70) and novel SCS (MD, –2.34; 95% CrI, –2.96 to –1.73). Leg pain intensity also decreased significantly with conventional SCS (MD, –2.89; 95% CrI, –4.03 to –1.81) and novel SCS (MD, –4.01; 95% CrI, –5.31 to –2.75) compared to CMM. Quality of life improved with both SCS therapies (conventional SCS MD, 0.15; 95% CrI, 0.09–0.21; novel SCS MD, 0.17; 95% CrI, 0.13–0.21). Functional disability improved significantly with conventional SCS (MD, –7.10; 95% CrI, –10.91 to –3.36).

Conclusions: Both conventional and novel SCS therapies are associated with significant improvements in pain relief, quality of life, and functional ability compared with CMM in patients with chronic back and leg pain at 6 months.

Implications for Practice: The results support integrating SCS therapies into clinical practice for patients with chronic back and leg pain unresponsive to CMM.

Study Strengths and Limitations: Strengths include inclusion of recent RCTs and use of Bayesian network meta-analysis, allowing comprehensive evidence synthesis with both direct and indirect comparisons, enhancing reliability. Limitations involve potential biases due to challenges in blinding participants and assessors, as patients can perceive whether a device is active. Heterogeneity among studies in patient populations and interventions may affect generalizability. Inability to include long-term efficacy data due to crossover in many trials limits understanding of sustained outcomes.

Future Research: Long-term RCTs are needed to assess sustained efficacy and safety of SCS therapies. Future studies should compare different SCS modalities directly and identify patient subgroups most likely to benefit.

Reference: Huygen FJPM, et al. Spinal Cord Stimulation vs Medical Management for Chronic Back and Leg Pain: A Systematic Review and Network Meta-Analysis. JAMA Network Open. 2024; doi: http://doi.org/10.1001/jamanetworkopen.2024.44608

 

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2023 VA/DoD Clinical Practice Guidelines for the Management of Headache

3 Nov, 2024 | 18:45h | UTC

Introduction: Headache disorders, notably migraine and tension-type headache (TTH), are among the most prevalent and disabling neurological conditions globally, significantly impacting individuals’ quality of life and imposing substantial societal costs. This 2023 guideline provides primary care clinicians with evidence-based recommendations for the evaluation, treatment, and prevention of migraine and TTH, aiming to enhance patient care and outcomes.

Key Recommendations:

1. Acute Migraine Treatment:
   • Triptans (eletriptan, frovatriptan, rizatriptan, sumatriptan, zolmitriptan) are strongly recommended for short-term migraine relief. (Strength: Strong for)
   • Aspirin–Acetaminophen–Caffeine combination is strongly recommended for acute migraine treatment. (Strength: Strong for)
   • Gepants (ubrogepant, rimegepant) are suggested as options for acute migraine management. (Strength: Weak for)
   • NSAIDs (aspirin, ibuprofen, naproxen) and acetaminophen are suggested for acute migraine relief. (Strength: Weak for)
2. Preventive Migraine Therapy:
   • CGRP Monoclonal Antibodies (erenumab, fremanezumab, galcanezumab) are strongly recommended for preventing episodic or chronic migraine. (Strength: Strong for)
   • Angiotensin Receptor Blockers (candesartan, telmisartan) are recommended for episodic migraine prevention. (Strength: Strong for)
   • Topiramate and valproate are suggested for migraine prevention. (Strength: Weak for)
   • Lisinopril, magnesium, memantine, and atogepant are suggested for preventing episodic migraine. (Strength: Weak for)
   • OnabotulinumtoxinA injections are suggested for preventing chronic migraine but not episodic migraine. (Strength: Weak for chronic migraine; Weak against for episodic migraine)
   • Gabapentin is not recommended for preventing episodic migraine. (Strength: Weak against)
3. Tension-Type Headache Management:
   • For acute TTH, ibuprofen (400 mg) or acetaminophen (1000 mg) are suggested. (Strength: Weak for)
   • Amitriptyline is suggested for preventing chronic TTH. (Strength: Weak for)
4. Nonpharmacologic Interventions:
   • Physical Therapy is suggested for managing TTH and migraine. (Strength: Weak for)
   • Aerobic Exercise or progressive strength training is suggested for preventing TTH and migraine. (Strength: Weak for)
5. Injections and Procedures:
   • Greater Occipital Nerve Block is suggested for short-term migraine treatment. (Strength: Weak for)

Conclusion: The 2023 VA/DoD Clinical Practice Guideline provides updated, evidence-based recommendations for managing migraine and TTH, incorporating new pharmacologic agents and nonpharmacologic interventions. The inclusion of newer medications, such as CGRP inhibitors, offers additional options for patients who may not respond to traditional therapies.

Reference: Sico JJ, et al. 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Management of Headache. Annals of Internal Medicine. 2023. DOI: http://doi.org/10.7326/ANNALS-24-00551

 

 

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RCT: Total Hip Replacement Superior to Resistance Training for Severe Hip Osteoarthritis

3 Nov, 2024 | 01:23h | UTC

Background: Severe hip osteoarthritis (OA) is often treated with total hip replacement (THR), yet randomized trials comparing THR with nonsurgical interventions like resistance training (RT) are lacking. While exercise is recommended for hip OA, its efficacy relative to surgery remains unclear.

Objective: To compare the effectiveness of THR with RT in patients aged 50 years or older with severe hip OA and an indication for surgery.

Methods: In a multicenter, randomized controlled trial, 109 patients were assigned to undergo THR (n=53) or participate in a 12-week supervised RT program (n=56). The primary outcome was the change in patient-reported hip pain and function from baseline to 6 months, measured by the Oxford Hip Score (OHS; range 0–48, higher scores indicate less pain and better function). Secondary outcomes included measures of pain, function, quality of life, physical activity, and functional performance. Safety was also assessed.

Results: At 6 months, the mean improvement in OHS was 15.9 points in the THR group and 4.5 points in the RT group (between-group difference: 11.4 points; 95% CI, 8.9 to 14.0; P<0.001). Significant improvements favoring THR were also observed in all secondary patient-reported outcomes. Serious adverse events occurred in 12% of patients in the THR group and 9% in the RT group; most were known complications of THR. At 6 months, 9% of patients assigned to THR had not undergone surgery, and 21% of those assigned to RT had undergone THR.

Conclusions: In patients aged 50 years or older with severe hip OA and an indication for surgery, THR resulted in clinically important, superior reductions in hip pain and improvements in function compared to RT at 6 months.

Implications for Practice: These findings support the use of THR over RT for patients with severe hip OA who are surgical candidates, affirming current clinical recommendations. However, RT may still be considered as an initial treatment option for some patients, especially those preferring to delay surgery.

Study Strengths and Limitations: Strengths include the randomized controlled design and multicenter approach. Limitations involve lack of blinding, potential selection bias due to low enrollment (14% of eligible patients), and crossovers between treatment groups, which may underestimate the true treatment effects.

Future Research: Further studies should investigate long-term outcomes, optimal timing of THR, and factors influencing patient choice and response to RT versus surgery.

Reference: Frydendal T, Christensen R, Mechlenburg I, et al. Total Hip Replacement or Resistance Training for Severe Hip Osteoarthritis. New England Journal of Medicine. 2024;391(17):1610-1620. DOI: http://doi.org/10.1056/NEJMoa2400141

 

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RCT: Vitamin K2 Reduces Nocturnal Leg Cramps in Older Adults

28 Oct, 2024 | 18:59h | UTC

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Psychedelic-Assisted Therapy May Reduce Anxiety and Depression in Patients with Life-Threatening Diseases

20 Oct, 2024 | 18:02h | UTC

Background: Anxiety, depression, and existential distress are prevalent among individuals facing life-threatening illnesses, significantly impacting their quality of life. Traditional treatments often have limited efficacy in this population. Psychedelic-assisted therapy, involving substances like psilocybin and LSD under professional supervision, has been proposed as a potential intervention. However, these substances are illegal in most countries and pose potential risks.

Objective: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators in treating anxiety, depression, and existential distress in people with life-threatening diseases.

Methods: This Cochrane systematic review included six randomized controlled trials conducted in the USA and Switzerland between 2011 and 2022. A total of 149 participants (140 analyzed), aged 36 to 64 years with life-threatening illnesses (e.g., cancer), were randomized to receive psychedelic-assisted therapy using classical psychedelics (psilocybin or LSD) or MDMA. Interventions included preparatory sessions, the psychedelic experience, and integration sessions. Comparators were active placebos (e.g., low-dose psychedelic or niacin) or placebo. Primary outcomes were anxiety, depression, and existential distress measured 1 to 12 weeks post-intervention.

Results: Psychedelic-assisted therapy with classical psychedelics may reduce anxiety and depression compared to active placebo:

• Anxiety: Mean difference (MD) of −8.41 points on the STAI-Trait scale (20–80 range; 95% CI, −12.92 to −3.89; 5 studies, 122 participants; low-certainty evidence).
• Depression: MD of −4.92 points on the Beck Depression Inventory (0–63 range; 95% CI, −8.97 to −0.87; 4 studies, 112 participants; low-certainty evidence).

The effect on existential distress was mixed and very uncertain. No treatment-related serious adverse events or grade 3/4 adverse events were reported. Common mild to moderate adverse events included elevated blood pressure, nausea, anxiety, and transient psychotic-like symptoms, which resolved shortly after the sessions.

Conclusions: Psychedelic-assisted therapy with classical psychedelics may reduce symptoms of anxiety and depression in patients with life-threatening diseases, but the evidence is of low certainty due to methodological limitations and small sample sizes. The effects of MDMA-assisted therapy are very uncertain.

Implications for Practice: While findings are promising, clinicians should exercise caution due to the low certainty of evidence and legal restrictions surrounding psychedelic substances.

Study Strengths and Limitations: Strengths include randomized designs and standardized therapeutic protocols involving preparation and integration sessions. Limitations are high risk of bias due to unblinding, small sample sizes, potential expectation bias, and cross-over designs with carry-over effects.

Future Research: Larger, well-designed RCTs with rigorous blinding are needed to confirm these findings. Future studies should explore long-term outcomes, diverse patient populations, and strategies to mitigate bias, such as using active placebos and measuring expectancy effects.

Reference: Schipper S, et al. (2024). Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database of Systematic Reviews. DOI: https://doi.org/10.1002/14651858.CD015383.pub2

 

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RCT: Low-Dose Amitriptyline Effective as Second-Line Treatment for Irritable Bowel Syndrome

20 Oct, 2024 | 15:56h | UTC

Background: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies—such as dietary changes and antispasmodic drugs—are ineffective, the UK National Institute for Health and Care Excellence (NICE) recommends considering low-dose tricyclic antidepressants as second-line treatment. However, their effectiveness in primary care is uncertain, and they are infrequently prescribed in this setting.

Objective: To determine whether titrated low-dose amitriptyline is effective as a second-line treatment for IBS in primary care.

Methods: In a randomized, double-blind, placebo-controlled, phase 3 trial (ATLANTIS) conducted at 55 general practices in England, 463 adults aged 18 years or older with Rome IV IBS and ongoing symptoms despite first-line therapies were randomized 1:1 to receive low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months. Dose titration over 3 weeks up to 30 mg once daily was allowed according to symptoms and tolerability. The primary outcome was the IBS Severity Scoring System (IBS-SSS) score at 6 months. Secondary outcomes included subjective global assessment (SGA) of relief of IBS symptoms, adequate relief for at least 50% of weeks, and adverse events.

Results: Among 463 participants (mean age 48.5 years; 68% female), low-dose amitriptyline was superior to placebo at 6 months, with a significant mean difference in IBS-SSS score between groups (–27.0; 95% CI, –46.9 to –7.1; P = .0079). More participants reported relief of IBS symptoms with amitriptyline compared to placebo (61% vs 45%; odds ratio [OR] 1.78; 95% CI, 1.19–2.66; P = .0050). Adequate relief of IBS symptoms for at least 50% of weeks was higher with amitriptyline (41% vs 30%; OR 1.56; 95% CI, 1.20–2.03; P = .0008). Adverse events were more frequent with amitriptyline, mainly related to anticholinergic effects such as dry mouth (54%) and drowsiness (53%), but most were mild. Withdrawals due to adverse events were slightly higher with amitriptyline (13% vs 9%).

Conclusions: Low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care and was safe and well tolerated.

Implications for Practice: General practitioners should consider prescribing low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, providing appropriate support for patient-led dose titration.

Study Strengths and Limitations: Strengths include the large sample size, primary care setting, and extended treatment duration. Limitations involve underrepresentation of patients with IBS with constipation, potential unblinding due to side effects, and a predominantly White participant population.

Future Research: Further trials assessing amitriptyline as a first-line therapy for IBS in primary care and studies on long-term outcomes are recommended.

Reference: Ford AC, Wright-Hughes A, Alderson SL, et al. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in Primary Care (ATLANTIS): a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet. 2023; DOI: http://doi.org/10.1016/S0140-6736(23)01523-4

 

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Meta-Analysis: Topiramate and CGRP Monoclonal Antibodies Effective in Medication Overuse Headache

13 Oct, 2024 | 14:07h | UTC

Background: Medication overuse headache (MOH) results from frequent intake of acute pain medications, leading to increased headache frequency and severity. There is ongoing debate regarding the necessity and optimal choice of prophylactic drugs in MOH treatment, with previous studies lacking clear guidance.

Objective: To determine the comparative efficacy and safety of available pharmacological therapies for MOH, including their ability to eliminate medication overuse (MO).

Methods: A systematic review and network meta-analysis of randomized controlled trials were conducted, comparing different pharmacological treatments for MOH. Primary outcomes included the responder rate (≥50% reduction in headache frequency), proportion of patients reverting to no medication overuse (nMO), and reductions in monthly headache days and acute medication intake frequency. The certainty of evidence was assessed using the GRADE framework.

Results: Twenty-eight studies involving 5,527 patients were included. Topiramate demonstrated significant benefits in increasing responder rates (odds ratio [OR] 4.93), reducing headache frequency (weighted mean difference [WMD] –5.53), and decreasing acute medication intake frequency (WMD –6.95), but was associated with more adverse events compared to placebo (OR 0.20). Fremanezumab, galcanezumab, and botulinum toxin type A (BTA) were effective in increasing responder rates (ORs 2.57 to 3.46). For reversion to nMO, eptinezumab, fremanezumab, and BTA were superior to placebo (ORs 1.55 to 2.75). Eptinezumab, fremanezumab, erenumab 140 mg, and BTA were more efficacious than erenumab 70 mg without significant differences in safety and tolerability.

Conclusions: Topiramate likely has large beneficial effects on increasing responder rates and reducing headache frequency but is associated with lower safety and greater intolerability. Fremanezumab, galcanezumab, and eptinezumab show promise in increasing responder rates. Eptinezumab has a large beneficial effect on reversion to nMO, with fremanezumab and BTA having smaller effects.

Implications for Practice: Clinicians should balance efficacy and tolerability when selecting pharmacological treatments for MOH. While topiramate is effective, its adverse event profile may limit its use. CGRP monoclonal antibodies, such as eptinezumab and fremanezumab, offer promising efficacy with acceptable safety profiles and may be preferred options for some patients.

Study Strengths and Limitations: Strengths include a comprehensive network meta-analysis of multiple pharmacological therapies and the use of GRADE for assessing evidence certainty. Limitations involve variability among included studies, small sample sizes, and heterogeneity in study populations and methodologies, which may affect the generalizability of the findings.

Future Research: High-quality randomized controlled trials are needed to confirm these findings and directly compare different pharmacological treatments in MOH. Future studies should focus on long-term efficacy, safety of newer therapies, and their impact on patient-centered outcomes.

Reference: Kong, F., Buse, D.C., Zhu, G., & Xu, J. (2024). Comparative efficacy and safety of different pharmacological therapies to medication overuse headache: a network meta-analysis. Journal of Headache and Pain. https://doi.org/10.1186/s10194-024-01878-0

 

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Network Meta-Analysis: Eletriptan, Rizatriptan, Sumatriptan, and Zolmitriptan Most Effective for Acute Migraine Episodes

23 Sep, 2024 | 22:34h | UTC

Background: Migraine, a highly prevalent neurological disorder, is a leading cause of disability, especially among women aged 15 to 49. Effective acute management is critical, with current guidelines recommending non-steroidal anti-inflammatory drugs (NSAIDs) and triptans for moderate to severe episodes. However, the relative efficacy of various drug interventions remains unclear, especially with newer treatments like lasmiditan and gepants entering the market.

Objective: To evaluate and compare the efficacy and tolerability of all licensed oral drugs for the acute treatment of migraine episodes in adults.

Methods: A systematic review and network meta-analysis was conducted, including 137 randomized controlled trials (RCTs) involving 89,445 participants. The study analyzed 17 drug interventions, including NSAIDs, triptans, ditans, and gepants, and compared them with placebo. Primary outcomes included pain freedom at two hours post-dose and sustained pain freedom from two to 24 hours post-dose. Certainty of evidence was assessed using the CINeMA framework, and sensitivity analyses were conducted to confirm the robustness of the findings.

Results: All active interventions outperformed placebo for pain freedom at two hours, with odds ratios ranging from 1.73 (95% CI 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan. The most effective drugs for sustained pain freedom were eletriptan and ibuprofen. Among head-to-head comparisons, eletriptan was the most effective for pain freedom at two hours, followed by rizatriptan, sumatriptan, and zolmitriptan. Newer drugs like lasmiditan, rimegepant, and ubrogepant were less effective than the triptans and showed adverse effects like dizziness and nausea.

Conclusions: Triptans—specifically eletriptan, rizatriptan, sumatriptan, and zolmitriptan—demonstrated superior efficacy and tolerability profiles compared to newer treatments like lasmiditan and gepants. Given their efficacy, these triptans should be prioritized in acute migraine management. However, triptans are underused, and barriers to access should be addressed to ensure broader utilization. Lasmiditan and gepants may still serve as alternatives for patients contraindicated for triptans due to cardiovascular risks.

Implications for Practice: Clinicians should prioritize triptans, particularly eletriptan, rizatriptan, sumatriptan, and zolmitriptan, in managing acute migraine episodes due to their superior efficacy. Careful consideration is needed when selecting newer drugs like lasmiditan and gepants, as they may be less effective and have higher costs and adverse event risks. Cost-effectiveness and patient cardiovascular profiles should guide decision-making.

Study Strengths and Limitations: Strengths include the comprehensive inclusion of both published and unpublished data, as well as the large sample size and robust methodological framework. Limitations include moderate heterogeneity and low confidence in some comparisons due to reporting biases and imprecise treatment effects in older studies.

Future Research: Future studies should focus on re-evaluating the cardiovascular contraindications of triptans to ensure broader access. Additional research is also needed to assess the cost-effectiveness of newer treatments like lasmiditan and gepants, particularly in patients for whom triptans are unsuitable.

Reference: Karlsson WK, et al. Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis. BMJ. 2024; DOI: https://doi.org/10.1136/bmj-2024-080107

 

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Systematic Review: Antidepressants Offer Limited Pain Relief with Potential Harms in Older Adults

17 Sep, 2024 | 11:34h | UTC

Background: Chronic pain is prevalent among older adults and significantly affects their quality of life. Antidepressants are commonly prescribed for pain management in this population across various countries. While several systematic reviews have evaluated the efficacy and safety of antidepressants for pain in adults, none have specifically focused on individuals aged 65 years and older. The efficacy and safety profile of antidepressants for pain relief in older adults remains unclear.

Objective: To assess the efficacy and safety of antidepressant medications compared to all alternatives for the management of non-cancer pain in older adults aged 65 years and above.

Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Thirteen databases were searched from inception to February 1, 2024, to identify relevant studies. Trials included compared any antidepressant medication to any alternative (e.g., placebo, other medications, or non-drug therapies) for the treatment of non-cancer pain in older adults. Data extracted included study and participant characteristics, primary efficacy outcomes (pain scores converted to a 0–100 scale), and harms. Estimates for efficacy were pooled using a random-effects model and reported as mean differences with 95% confidence intervals (CIs). The quality of included trials was assessed using the Cochrane risk of bias tool.

Results: Fifteen studies encompassing 1,369 participants met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (six studies each). Pain related to knee osteoarthritis was the most commonly studied condition (six studies). For knee osteoarthritis:

• Immediate Term (0–2 weeks): Antidepressants did not provide a statistically significant reduction in pain compared to alternatives (mean difference [MD], –5.6; 95% CI, –11.5 to 0.3).
• Intermediate Term (≥6 weeks and <12 months): Duloxetine provided a statistically significant, albeit very small, reduction in pain (MD, –9.1; 95% CI, –11.8 to –6.4).

Nearly half of the studies (7 out of 15) reported increased withdrawal of participants in the antidepressant treatment group compared to the comparator group due to adverse events.

Conclusions: For most chronic painful conditions in older adults, the benefits and harms of antidepressant medications are unclear. The available evidence predominantly comes from trials with small sample sizes (less than 100 participants), disclosed industry ties, and trials classified as having unclear or high risk of bias.

Implications for Practice:

• Minimal Benefit: Antidepressants, particularly duloxetine, may offer a very small benefit for pain relief in older adults with knee osteoarthritis over the intermediate term.
• Risk of Harms: The potential harms, including increased adverse events leading to higher withdrawal rates, may outweigh these minimal benefits.
• Clinical Decision-Making: Clinicians should carefully weigh the benefits against the risks when considering prescribing antidepressants for pain in older adults.
• Alternative Strategies: Non-pharmacological interventions and alternative pain management strategies should be prioritized in this population.

Study Strengths and Limitations: Strengths include the comprehensive search strategy across multiple databases and the focus on older adults, a population often underrepresented in clinical trials. Limitations involve the generally low quality of the included trials, small sample sizes, high risk of bias, and inconsistent reporting of pain outcomes and adverse events among studies.

Future Research: Further large-scale, high-quality randomized controlled trials are needed to investigate the efficacy and safety of antidepressants for pain management in older adults. Future studies should also compare antidepressants to non-pharmacological interventions and explore long-term outcomes and optimal dosing regimens in this population.

Reference: Narayan SW, Naganathan V, Vizza L, et al. Efficacy and Safety of Antidepressants for Pain in Older Adults: A Systematic Review and Meta-Analysis. Br J Clin Pharmacol. Published online September 12, 2024. doi:10.1111/bcp.16234

 

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RCT: Methotrexate Shows Modest Pain Reduction in Knee Osteoarthritis, More Research Needed – Ann Intern Med

18 Aug, 2024 | 18:01h | UTC

Study Design and Population: This multicenter, randomized, double-blind, placebo-controlled trial evaluated the effects of oral methotrexate on 207 participants with symptomatic knee osteoarthritis (KOA) who had persistent knee pain despite prior treatments. Conducted across 15 musculoskeletal clinics in the UK from June 2014 to October 2017, participants were randomly assigned to receive either methotrexate or placebo over a 12-month period.

Main Findings: At 6 months, methotrexate resulted in a modest reduction in knee pain, with a statistically significant difference of 0.79 points on the NRS compared to placebo (95% CI, 0.08 to 1.51; P = 0.030). Small but statistically significant improvements were also noted in knee stiffness and function. However, the clinical significance of these findings remains uncertain, and potential side effects of methotrexate warrant caution.

Implications for Practice: While methotrexate may offer some symptomatic relief for patients with knee osteoarthritis who do not respond to standard treatments, the modest reduction in pain and improvement in function observed in this study may not justify its routine use given the potential for significant side effects. The small magnitude of benefit suggests that methotrexate should be considered cautiously and only in select patients. Further research is necessary to confirm these findings and to better understand the risk-benefit profile of methotrexate in this population before broader clinical adoption.

Reference: Kingsbury, S. R., Tharmanathan, P., Keding, A., Watt, F. E., Scott, D. L., Roddy, E., Birrell, F., & Conaghan, P. G. (2024). Pain Reduction With Oral Methotrexate in Knee Osteoarthritis: A Randomized, Placebo-Controlled Clinical Trial. Annals of Internal Medicine. DOI: 10.7326/M24-0303.

 

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Cohort Study: Prenatal opioid exposure linked to modest increase in neuropsychiatric disorders – The BMJ

25 May, 2024 | 19:50h | UTC

This nationwide birth cohort study from South Korea investigated the impact of prenatal opioid exposure on the risk of neuropsychiatric disorders among children. The study followed 3,128,571 infants born between 2010 and 2017 until the end of 2020. Researchers found that infants exposed to opioids prenatally showed a slightly increased risk of developing neuropsychiatric disorders, including mood disorders, attention deficit hyperactivity disorder, and intellectual disability. The increased risk was more pronounced with higher opioid doses, longer duration of use, and exposure during the first trimester of pregnancy. However, this association was not significant in sibling comparison cohorts, indicating a modest overall clinical impact. The study emphasizes the need for cautious interpretation due to its observational design and the specific conditions under which risk increases.

 

Reference (link to free full-text):

Jiseung Kang et al. (2024). Prenatal opioid exposure and subsequent risk of neuropsychiatric disorders in children: nationwide birth cohort study in South Korea. BMJ, 385, e077664. DOI: https://doi.org/10.1136/bmj-2023-077664

 

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RCT: Triple combination of paracetamol, ibuprofen, and dexamethasone reduces morphine use post-hip arthroplasty – Lancet Rheumatol

11 May, 2024 | 14:18h | UTC

Study Design and Population: The RECIPE trial was a randomized, blinded, placebo-controlled multicenter study conducted across nine Danish hospitals to evaluate the effectiveness of non-opioid analgesic combinations in managing postoperative pain following total hip arthroplasty. A total of 1,060 adults scheduled for surgery were enrolled and randomly assigned to one of four treatment groups, receiving combinations of paracetamol, ibuprofen, and dexamethasone. The study’s primary endpoint was the 24-hour intravenous morphine consumption, with a predefined minimal important difference set at 8 mg.

Main Findings: The trial results indicated significant reductions in 24-hour morphine consumption in the group receiving paracetamol, ibuprofen, and dexamethasone combined, compared to other groups, though none reached the minimal important difference. Specifically, this group consumed a median of 15 mg morphine, which was less than the other groups ranging from 16 mg to 24 mg. However, the differences did not meet the study’s threshold for a clinically important effect. Adverse events were lowest in the combined treatment group, suggesting a better safety profile primarily characterized by fewer incidents of nausea, vomiting, and dizziness.

Implications for Practice: The findings support the use of a combined regimen of paracetamol, ibuprofen, and dexamethasone for reducing morphine consumption post-total hip arthroplasty, which could be significant in clinical settings aiming to minimize opioid use. The improved safety profile also highlights the potential benefits of multimodal analgesia. Further research may explore the optimization of dosing schedules and long-term outcomes to enhance patient recovery and satisfaction.

 

Reference (link to abstract – $ for full-text):

Steiness J et al. (2024). Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial. The Lancet Rheumatology, 6(4), e205-e215. DOI: 10.1016/S2665-9913(24)00020-1

 

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RCT: Serratus anterior plane block reduces pain and opioid use in rib fracture patients – JAMA Surgery

2 May, 2024 | 23:20h | UTC

Study Design and Population:
This study was a multicenter, open-label, pragmatic randomized clinical trial conducted across eight emergency departments in New South Wales, Australia. The trial included 210 patients aged 16 years or older who had clinically suspected or radiologically confirmed rib fractures. Patients intubated, transferred for urgent surgical intervention, or with major concomitant nonthoracic injuries were excluded.

 

Main Findings:
In the trial, patients were randomized to receive either a serratus anterior plane block (SAPB) along with standard rib fracture management or standard care alone. The primary outcome was a composite pain score measured 4 hours post-enrollment. The SAPB group showed a significant increase in patients achieving the desired pain score reduction (41% in SAPB group vs. 19.6% in control; RR 0.73, 95% CI 0.60-0.89, P = 0.001). Additionally, SAPB recipients had significantly lower opioid consumption at 24 hours compared to the control group.

 

Implications for Practice:

The trial’s results support the addition of a serratus anterior plane block (SAPB) to standard rib fracture management for providing effective early pain relief and reducing opioid use. However, it’s important to note that this study did not include a sham group, and patients were aware of whether they received the intervention. This lack of blinding could influence patient-reported outcomes due to placebo effects. Despite this limitation, the reduction in pain and opioid consumption suggests that SAPB is a beneficial component of care for patients with rib fractures.

 

Reference (link to abstract – $ for full-text):

Reference: Partyka, C. et al. (2024). Serratus Anterior Plane Blocks for Early Rib Fracture Pain Management The SABRE Randomized Clinical Trial. JAMA Surg. Published online May 1, 2024. DOI: 10.1001/jamasurg.2024.0969

 

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Cohort Study: No increased risk of autism, ADHD, or intellectual disability from acetaminophen use in pregnancy

29 Apr, 2024 | 12:34h | UTC

This cohort study investigated the association between acetaminophen use during pregnancy and the risk of autism, ADHD, and intellectual disability in children. The study utilized a population-based sample of nearly 2.5 million Swedish children born between 1995 and 2019, with data analyzed up to 2021. Initial findings without sibling controls suggested a marginal increase in the risks of autism and ADHD. However, sibling control analyses, which help adjust for familial confounding, showed no significant associations (HR for autism and ADHD at 0.98, and intellectual disability at 1.01). These results imply that earlier observed risks might be due to unaccounted familial factors, not acetaminophen exposure.

 

Reference (link to abstract – $ for full-text):

Viktor H. Ahlqvist et al. (2024). Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA, 331(14), 1205-1214. DOI: 10.1001/jama.2024.3172

 

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Phase 2 Trials | Selective NaV1.8 inhibitor, VX-548, shows potential in acute postoperative pain management

7 Aug, 2023 | 14:51h | UTC

Selective Inhibition of NaV1.8 with VX-548 for Acute Pain – New England Journal of Medicine (link to abstract – $ for full-text)

Video Summary: Selective Inhibition of NaV1.8 for Acute Pain | NEJM

Commentaries:

High-Dose VX-548 Reduces Acute Pain Post-Surgery – HCP Live

High-Dose VX-548 Reduces Acute Pain Over 48 Hours – HealthDay

 

Commentary on Twitter

Original Article: Selective Inhibition of NaV1.8 with VX-548 for Acute Pain https://t.co/ogmEx6FNKo#surgery pic.twitter.com/0FpipA1xey

— NEJM (@NEJM) August 5, 2023

 

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RCT | Atogepant outperforms placebo in reducing migraines over 12 weeks

2 Aug, 2023 | 13:56h | UTC

Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial – The Lancet (link to abstract – $ for full-text)

 

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Review | Painful diabetic peripheral neuropathy

20 Jul, 2023 | 10:53h | UTC

Painful Diabetic Peripheral Neuropathy: Practical Guidance and Challenges for Clinical Management – Diabetes, Metabolic Syndrome and Obesity

 

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Clinical practice guideline for deprescribing opioid analgesics

12 Jul, 2023 | 13:58h | UTC

Clinical practice guideline for deprescribing opioid analgesics: summary of recommendations – Medical Journal of Australia

Related:

RCT | Opioids not more effective than placebo for acute low back and neck pain

Deprescribing considerations for older people in general practice – Australian Journal of General Practice

Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review – Journal of Clinical Medicine

An Overview of Systematic Reviews and Meta-Analyses on the Effect of Medication Interventions Targeting Polypharmacy for Frail Older Adults – Journal of Clinical Medicine

Physician-led medication reviews in polypharmacy patients treated with at least 12 medications in a type 2 diabetes outpatient clinic: a randomised trial – Diabetic Medicine

RCT | A deprescribing intervention reduced medication burden among older adults in post-acute care

Achieving sustainable healthcare through deprescribing of unnecessary medications: making sense of the evidence – Cochrane Library

Deprescribing medicines in older people living with multimorbidity and polypharmacy: the TAILOR evidence synthesis – Health Technology Assessment

Barriers and facilitators to deprescribing of cardiovascular medications: a systematic review – BMJ Open

A National Modified Delphi Consensus Process to Prioritize Experiences and Interventions for Antipsychotic Medication Deprescribing Among Adult Patients With Critical Illness – Critical Care Explorations

Deprescribing proton pump inhibitors – Australian Journal of General Practice

Medication reviews and deprescribing as a single intervention in falls prevention: a systematic review and meta-analysis – Age and Ageing

Optimizing Medication Use in Older Adults With Rheumatic Musculoskeletal Diseases: Deprescribing as an Approach When Less May Be More – ACP Open Rheumatology

Facing the challenge of polypharmacy when prescribing for older people with cardiovascular disease. A review by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy – European Heart Journal – Cardiovascular Pharmacotherapy

Deprescribing in Older Adults with Cardiovascular Disease – Journal of the American College of Cardiology

Multimorbidity in Older Adults with Cardiovascular Disease – American College of Cardiology, Latest in Cardiology

Antihypertensive Deprescribing in Older Adults: a Practical Guide – Current Hypertension Reports

How-to guide for medication reviews in older adults with cancer: A Young International Society of Geriatric Oncology and Nursing & Allied Health Interest Group initiative – Journal of Geriatric Oncology

Deprescribing in Palliative Cancer Care – Life

Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review – Kidney360

Process evaluation of implementation strategies to reduce potentially inappropriate medication prescribing in older population: A scoping review – Research in Social and Administrative Pharmacy

AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review – Gastroenterology

Development of a Metric to Detect and Decrease Low-Value Prescribing in Older Adults – JAMA Network Open

The MedSafer Study—Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial – JAMA Internal Medicine

Quantifying Anticholinergic Burden and Sedative Load in Older Adults with Polypharmacy: A Systematic Review of Risk Scales and Models – Drugs & Aging

Deprescribing in palliative patients with cancer: a concise review of tools and guidelines – Supportive Care in Cancer

Prescribing practices, patterns, and potential harms in patients receiving palliative care: A systematic scoping review – Exploratory Research in Clinical and Social Pharmacy

A narrative review of evidence to guide deprescribing among older adults – Journal of General and Family Medicine

Polypharmacy, inappropriate prescribing, and deprescribing in older people: through a sex and gender lens – The Lancet Health Longevity

Polypharmacy Management in Older Patients – Mayo Clinic Proceedings

Psychopharmacological Treatment in Older People: Avoiding Drug Interactions and Polypharmacy – Deutsches Ärzteblatt international

Eliminating Medication Overload: A National Action Plan – Lown Institute

International Group for Reducing Inappropriate Medication Use & Polypharmacy (IGRIMUP): Position Statement and 10 Recommendations for Action – Drugs & Aging

Common ED Medication Errors: Polypharmacy – emDocs

Current and future perspectives on the management of polypharmacy – BMC Family Practice

Routine deprescribing of chronic medications to combat polypharmacy – Therapeutic Advances in Drug Safety

Polypharmacy—an Upward Trend with Unpredictable Effects – Deutsches Ärzteblatt international

Clinical Consequences of Polypharmacy in Elderly – Expert Opinion on Drug Safety

 

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