klinik farmakoloji dosyası

Gabapentin (Neurontin ve benzerleri), pregabalin (Lyrica ve benzerleri) beş ağrılarında etkisiz veya çok az etkili olmasına ragmen ciddi yan etkilere sahip. Yeni yapılan araştırmada gabapentin (Neurontin, Gabaset, Gabateva, Gabanyl, Gemuda, Patyca vs…) placebo ile karşılaştırıldığında minimum etki tesbit edilmiş. Pregabalin (Lyrica, Alyse, Galara, Lir, Neogaba,Paden,Pagamax, Perge, Pigus, Spesicor,Zenixa, vs..). üç çalışmada diğer tip ağrı kesicilerrle kıyaslandığında diğer ağrı kesicilerin pregabalinden daha etkili olduğu ortaya çıkmıştır. Pregabalinin tapentadol (Nucynta, opioid) ile kombinasyonunda da bir fayda elde edilememiştir. Çalışmalarda ölüme rastlanmamıştır. Plasebo grubundan anlamlı olarak seremlik, bitkinlik, dunce zorluğu ve mental aktivite bozukluğu ve görme bozuklukları gabapentin ve pregabalin gruplarında yüksek bulunmuştur.
SONUÇ: gabapentinoidler ciddi yan etkileri yanında hastalara anlamlı bir fayda sağlamamaktadır

Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials
Harsha Shanthanna , Ian Gilron, Manikandan Rajarathinam, Rizq AlAmri, Sriganesh Kamath, Lehana Thabane, Philip J. Devereaux,
Plos Medicine: Published: August 15, 2017, 
Background and objective
Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin (GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients.
Electronic databases of MEDLINE, EMBASE, and Cochrane were searched from their inception until December 20th, 2016. We included randomized control trials reporting the use of gabapentinoids for the treatment of CLBP of >3 months duration, in adult patients. Study selection and data extraction was performed independently by paired reviewers. Outcomes were guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief and safety as the primary outcomes. Meta-analyses were performed for outcomes reported in 3 or more studies. Outcomes were reported as mean differences (MDs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs), and I2 in percentage representing the percentage variability in effect estimates that could be explained by heterogeneity. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of evidence.
Out of 1,385 citations, eight studies were included. Based on the interventions and comparators, studies were analyzed in 3 different groups. GB compared with placebo (3 studies, n = 185) showed minimal improvement of pain (MD = 0.22 units, 95% CI [−0.5 to 0.07] I2 = 0%; GRADE: very low). Three studies compared PG with other types of analgesic medication (n = 332) and showed greater improvement in the other analgesic group (MD = 0.42 units, 95% CI [0.20 to 0.64] I2 = 0; GRADE: very low). Studies using PG as an adjuvant (n = 423) were not pooled due to heterogeneity, but the largest of them showed no benefit of adding PG to tapentadol. There were no deaths or hospitalizations reported. Compared with placebo, the following adverse events were more commonly reported with GB: dizziness-(RR = 1.99, 95% CI [1.17 to 3.37], I2 = 49); fatigue (RR = 1.85, 95% CI [1.12 to 3.05], I2 = 0); difficulties with mentation (RR = 3.34, 95% CI [1.54 to 7.25], I2 = 0); and visual disturbances (RR = 5.72, 95% CI [1.94 to 16.91], I2 = 0). The number needed to harm with 95% CI for dizziness, fatigue, difficulties with mentation, and visual disturbances were 7 (4 to 30), 8 (4 to 44), 6 (4 to 15), and 6 (4 to 13) respectively. The GRADE evidence quality was noted to be very low for dizziness and fatigue, low for difficulties with mentation, and moderate for visual disturbances. Functional and emotional improvements were reported by few studies and showed no significant improvements.
Conclusions and relevance
Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue.
Commonly prescribed drugs for back pain often ineffective, review says
Existing studies do not support use or show benefits for gabapentin
• Benefits and safety of gabapentinoids in chronic low back pain
• Pregabalin and gabapentin: advice for prescribers on the risk of misuse, NHS England
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Doctors are prescribing anti-seizure and nerve pain medications for a common type of chronic low-back pain, a non-licensed use, despite a lack of studies supporting their effectiveness for that purpose, according to a new review.
The drugs, known as gabapentinoids, include gabapentin (originally marketed under the brand name Neurontin) and pregabalin (previously sold as Lyrica alone). Health Canada approved gabapentin to treat epilepsy that isn't controlled by conventional therapy, and pregablin is indicated for types of nerve pain. 
Both medications are also prescribed for non-licensed uses, including non-specific chronic lower back pain that doesn't involve nerves in the legs and whose cause can't be traced. About 90 to 95 per cent of adults experience low back pain at some point.
In Tuesday's issue of the journal PLOS Medicine, Dr. Harsha Shanthanna, an anesthesiologist and associate professor in the anesthesia department at McMaster University in Hamilton, and his team analyzed eight randomized controlled trials on use of the drugs among adults with chronic low back pain.
"There are very few studies that allow physicians to make informed decisions. That's probably one of the most important findings," Shanthanna said in an interview. "Whatever studies do exist do not support its use or do not show a benefit in the form of pain relief."
In 2004, after Neurontin's patent expired, Pfizer admitted to fraudulently marketing gabapentin. In 2012, Pfizer settled over its misleading promotional claims of pregabalin.
The other main finding, Shanthanna said, was that four side-effects were common with these medications:
• Dizziness.
• Fatigue.
• Difficulties with thinking or mental activity.
• Visual disturbances.
Family doctors, neurologists and chronic pain physicians prescribe the medications.
Shanthanna said physicians are thoughtful and careful when choosing pain medications for individual patients, which tends to be based on trial and error. "What we emphasize in our review is we've got to be more cautious."
He called for more research to guide physicians.
"This should actually make us do more studies so that we can more definitely and more conclusively inform ourselves rather than getting a skewed picture." 
Canada's Patented Medicine Prices Review Board notes that between 2011 to 2013, about one-third of new gabapentin users had used opioids just before switching.
The Canadian site notes increasing misuse of gabapentin, as does Ohio's Substance Abuse Monitoring. In 2014 in England, the National Health Service's advisory warned of misuse potential for both gabapentin and pregabalin, along with suggestions on using the medicines.
Alternatives to drugs needed
Earlier this month, Dr. Christopher Goodman and Dr. Allan Brett of the South Carolina School of Medicine wrote a commentary in the New England Journal of Medicine about increased prescribing of gabapentin and pregabalin for pain.
"We suspect that clinicians who are desperate for alternatives to opioids have lowered their thresholds for prescribed gabapentinoids to patients with various types of acute, subacute, and chronic non-cancer pain," Goodman and Brett wrote.
They said indiscriminate off-label use of gabapentinoids reinforces the tendency of clinicians to view pain treatment through a pharmacologic lens.
Rather, the pair wrote, for clinicians to manage both acute and chronic pain appropriately, they need to spend time assessing how the patient's pain affects their activity and function to mitigate it, not necessarily eliminate it.
But non-pharmacologic approaches, such as cognitive behavioural therapy or referrals to multidisciplinary pain clinics, may be unavailable or unaffordable, they said.