Articles: placebo.
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Randomized Controlled Trial
METHA-NeP: effectiveness and safety of methadone for neuropathic pain: a controlled randomized trial.
In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. ⋯ No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.
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The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics. ⋯ Approaches using membrane transporters and receptor-mediated transcytosis are less invasive than are other techniques, but they can have off-target effects. Nanotherapeutics have shown promise, but these strategies are in early stages of development. Advancements in drug delivery across the blood-brain barrier will require appropriately designed and powered clinical studies, with a focus on the timing of treatment, demographic and genetic considerations, head-to-head comparison with other treatment strategies (rather than a placebo), and relevant primary and secondary outcome measures.
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Treatment expectations (TE) are predictive of patient outcomes in clinical practice and suggested to moderate treatment responses in chronic pain clinical trials. However, evidence is mainly derived from studies conducted with adult populations with musculoskeletal pain, primarily focused on pharmacological treatments and a few alternative intervention modalities (e.g., acupuncture). We examined the role of pretreatment TE in youth participating in two randomized controlled trials of digital cognitive-behavioral therapy (CBT) for chronic pain-the WebMAP2 Trial of youth with chronic primary pain (n = 273) and the iCC-SCD Trial of youth with sickle cell pain (n = 111). ⋯ Overall, higher pretreatment TE were associated with better functioning over time, though the specific domains of improvement and the moderating effects on treatment efficacy somewhat differed between youth with primary and sickle cell-related chronic pain. PERSPECTIVE: Incorporating TE into clinical assessments and ensuring consistent collection, reporting, and analysis in clinical trials are crucial for identifying potential heterogeneous treatment responses. Standardizing TE measures for youth with chronic pain and considering population characteristics are important for understanding TE's role in treatment responses.
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Socioeconomic Position (SEP) is a multidimensional construct encompassing education, income, occupation, and neighborhood distress, influencing chronic pain severity, interference, and duration. However, its impact on placebo analgesia, where reduced pain perception occurs due to treatment belief, remains understudied. Using a quasi-experimental approach, we investigated SEP's influence on placebo analgesia in 401 participants with temporomandibular disorder (TMD) and 400 pain-free individuals. ⋯ PERSPECTIVE: SEP significantly contributes to pain disparities. This quasi-experimental study demonstrates analogous placebo analgesia between chronic pain and pain-free individuals but finds lower placebo analgesia only among individuals with chronic pain and distressed SEP. This highlights a link between chronic pain, SEP, and impaired placebo effects, suggesting new avenues for research.