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Depression is the third leading cause of disability in the world. Depressive symptoms may be reduced within several weeks after the start of conventional antidepressants, but treatment resistance concerns one-third of patients who fail to achieve recovery. Over the last 20 years, ketamine, an antagonist of the N-methyl-D-aspartate receptor, has been described to have antidepressant properties. A literature review was conducted through an exhaustive electronic search. It was restricted to Cochrane reviews, meta-analyses, and randomized controlled trials (RCTs) of ketamine for major depressive disorder and/or bipolar disorder. This review included two Cochrane reviews, 14 meta-analyses and 15 trials. Ketamine was studied versus placebo, versus other comparators and as an anesthetic adjuvant before electroconvulsive therapy. In 14 publications, ketamine provided a rapid antidepressant effect with a maximum efficacy reached at 24 hrs. Its effect lasted for 1-2 weeks after infusion, but a longer-term effect is little reported. Ketamine does not seem to improve depressive symptoms at the end of electroconvulsive sessions. Safety and tolerability profiles with ketamine at low single dose are generally good in depressed patients. However, there is a lack of data concerning ketamine with repeated administration at higher doses. The clinical use of ketamine is increasing. Intranasal (S)-ketamine has recently been approved for depression by the Food and Drug Administration. It could be a promising treatment in depressed patients with suicidal ideation. Collectively, the level of proof of efficacy remains low and more RCTs are needed to explore efficacy and safety issues of ketamine in depression.

The prevalence of neuropathic pain in the older population has been reported to be very high and is most commonly localized to a circumscribed area. Treatment failure is frequent in neuropathic pain and is accompanied by central side effects with recommended oral drugs acting on the central nervous system. A number of topical pharmaceuticals are available on prescription and also sold over the counter. This review in persons aged older than 60 years shows the efficacy of lidocaine 5% and capsaicin 8% for localized neuropathic pain while results with other pharmaceuticals are rather inconsistent. Local application of drugs has a very limited systemic effect and the pharmacological advantages of local over systemic treatment are particularly interesting in older persons who often have comorbidities and take multiple medications. However, more information is needed on the efficacy and safety of lidocaine 5% and capsaicin 8% in older old persons and on the long-term effects of these pharmaceuticals. These studies should also pave the way for research and development in the field of topical analgesics with a satisfactory level of evidence-based medicine.

Magnesium deficiency and stress are both common conditions among the general population, which, over time, can increase the risk of health consequences. Numerous studies, both in pre-clinical and clinical settings, have investigated the interaction of magnesium with key mediators of the physiological stress response, and demonstrated that magnesium plays an inhibitory key role in the regulation and neurotransmission of the normal stress response. Furthermore, low magnesium status has been reported in several studies assessing nutritional aspects in subjects suffering from psychological stress or associated symptoms. This overlap in the results suggests that stress could increase magnesium loss, causing a deficiency; and in turn, magnesium deficiency could enhance the body’s susceptibility to stress, resulting in a magnesium and stress vicious circle. This review revisits the magnesium and stress vicious circle concept, first introduced in the early 1990s, in light of recent available data.

The effect of a combination of magnesium, vitamins B6, B9, B12, rhodiola and green tea/L-theanine (Mg-Teadiola) on stress was evaluated in chronically stressed, otherwise healthy individuals. Effects on stress-related quality-of-life parameters (sleep and perception of pain) were also explored. Adults with stress for ≥1 month, scoring ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire, were randomized (1:1) to receive oral Mg-Teadiola (n = 49) or a placebo (n = 51), for 28 days, with a follow-up assessment on Day 56 (NCT04391452). The primary endpoint was the change in the DASS-42 stress score from baseline to Day 28 with Mg-Teadiola versus placebo. The DASS-42 stress scores significantly decreased from baseline to Day 28 with Mg-Teadiola versus placebo (effect size, 0.29; 95% CI [0.01, 0.57]; p = 0.04). Similar reductions were observed on Day 14 (p = 0.006) and Day 56 (p = 0.02). A significant reduction in sensitivity to cold pain (p = 0.01) and a trend for lower sensitivity to warm pain was observed (p = 0.06) on Day 28. Improvements in daytime dysfunction due to sleepiness (Pittsburgh Sleep Quality Index-7 component score) were reported on Day 28, and were significant on Day 56 (p < 0.001). Mg-Teadiola is effective in managing stress in otherwise healthy individuals. Its beneficial effects on sleep and pain perception need further investigation.

Topical lidocaine is widely used in current practice for a variety of pain conditions. This literature review shows that its limited absorption and relative lack of systemic adverse events are an attractive analgesic option for a number of vulnerable patients. Topical lidocaine has been approved by health authorities for the treatment of post-herpetic neuralgia in a number of countries, and studies present some degree of evidence of its efficacy and safety in postsurgical pain, diabetic peripheral neuropathy, carpal tunnel syndrome, chronic lower back pain and osteoarthritis. Topical lidocaine may be a great alternative alone or in addition to systemic drugs and non-pharmacological approaches for an optimized pain management and in multimodal analgesia.

Background: Ketamine use for chronic pain and depression has increased worldwide, but sex differences in its efficacy and safety have been little studied; this study examines existing evidence to address this gap. Methods: A prospective, multicenter, one-year observational study in 585 chronic pain patients was performed; 256 patients had one administration of ketamine and 329 had two or more. The primary outcome looked at was mean pain intensity (0–10), assessed every month for 1 year by telephone. Secondary outcomes included measures of depression and anxiety (assessed using the Hospital Anxiety and Depression Scale), quality of life (evaluated with the 12-item Short Form Health Survey), total ketamine dosage, reported adverse effects, and concomitant treatments. Platform of Clinical Investigation, No sex or age differences were observed in ketamine efficacy in terms of pain (mean variation in women vs. men; effect size −0.5 (95% confidence interval −0.6 to −0.4) vs. −0.5 (95% confidence interval −0.7 to −0.3), p = 0.248) or the evolution of anxiety (p = 0.135) among the 585 patients. Women reported more adverse events than men (19% vs. 13%, p = 0.002). In the subgroup of 329 patients, no differences were observed in any variables, but a single ketamine administration may be more useful in men than in women (p = 0.032), especially in younger men (p = 0.045). Conclusions: Repeated ketamine administration displayed no sex or age differences in efficacy in the treatment of pain, anxiety or depression.

Background: Magnesium (Mg) is commonly used in clinical practice for acute and chronic pain and has been reported to reduce pain intensity and analgesics consumption in a number of studies. Results are, however, contested. Objectives: This review aims to investigate randomised clinical trials (RCTs) on the effectiveness of Mg treatment on pain and analgesics consumption in situations including post-operative pain, migraine, renal pain, chronic pain, neuropathic pain and fibromyalgia. Results: The literature search identified 81 RCTs (n = 5447 patients) on Mg treatment in pain (50 RCTs in post-operative pain, 18 RCTs in migraine, 5 RCTs in renal pain, 6 RCTs in chronic/neuropathic pain, 2 RCTs in fibromyalgia). Conclusion: The level of evidence for the efficacy of Mg in reducing pain and analgesics consumption is globally modest and studies are not very numerous in chronic pain. A number of gaps have been identified in the literature that need to be addressed especially in methodology, rheumatic disease, and cancer. Additional clinical trials are needed to achieve a sufficient level of evidence and to better optimize the use of Mg for pain and pain comorbidities in order to improve the quality of life of patients who are in pain.

Objective Pain evaluation scales often rely on the sense of sight. There is so far no pain assessment scale designed specifically for persons with visual impairment. Design This study aims to validate a tactile pain evaluation scale, Visiodol (Copyright Prof Pickering), in blind or visually impaired persons, by correlation with a numeric pain scale. Setting The study took place at University Hospital Clermont-Ferrand, France. Methods Pain intensity for a range of thermal stimuli (Pathway Medoc) was evaluated with Visiodol and a numeric pain scale. Secondary outcomes, including pain thresholds, catastrophizing, emotion, and quality of life, were compared in persons who were blind or visually impaired and in sighted persons. Lin’s concordance correlation coefficient was estimated. Weighted Cohen’s κ accounted for degrees of disagreement between scales with 95% confidence intervals (95% CI). Subjects Sixteen healthy sighted and 21 healthy nonsighted volunteers (n = 13 congenital, n = 8 acquired) were included. Results Lin’s correlation coefficient for repeated data was 0.967 (95% CI, 0.956–0.978; P < 0.001) for visually impaired participants, with a good agreement at each temperature plateau. A weighted Cohen’s κ of 0.90 (95% CI, 0.84–0.92) and 92.9% percentage of agreement for visually impaired participants were satisfactory. Pain perception, psychological components, and quality of life were more impaired in persons who were blind or visually impaired than in sighted persons. Conclusions This study validates Visiodol, a tactile scale for persons who are blind or visually impaired, and addresses health care inequalities in the context of pain evaluation. Visiodol will now be tested in a larger population of patients to give the millions of persons worldwide who are blind or visually impaired an option for pain intensity evaluation in clinical situations. Trial registration French National Agency for the Safety of Medicines and Healthcare Products (2018-A03370-55) and www.ClinicalTrials.gov (NCT03968991).

Neuropathic pain frequently affects older people, who generally also have several comorbidities. Elderly patients are often poly-medicated, which increases the risk of drug–drug interactions. These patients, especially those with cognitive problems, may also have restricted communication skills, making pain evaluation difficult and pain treatment challenging. Clinicians and other healthcare providers need a decisional algorithm to optimize the recognition and management of neuropathic pain. We present a decisional algorithm developed by a multidisciplinary group of experts, which focuses on pain assessment and therapeutic options for the management of neuropathic pain, particularly in the elderly. The algorithm involves four main steps: (1) detection, (2) evaluation, (3) treatment, and (4) re-evaluation. The detection of neuropathic pain is an essential step in ensuring successful management. The extent of the impact of the neuropathic pain is then assessed, generally with self-report scales, except in patients with communication difficulties who can be assessed using behavioral scales. The management of neuropathic pain frequently requires combination treatments, and recommended treatments should be prescribed with caution in these elderly patients, taking into consideration their comorbidities and potential drug–drug interactions and adverse events. This algorithm can be used in the management of neuropathic pain in the elderly to ensure timely and adequate treatment by a multidisciplinary team.

Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.