Pharmacologic interventions for treating phantom limb pain.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP. OBJECTIVES: This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and Embase for relevant studies. We ran the searches for the original review in September 2011 and subsequent searches for this update up to April 2016. We sought additional studies from clinical trials databases and reference lists of retrieved papers. SELECTION CRITERIA: We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions compared with placebo, another active treatment, or no treatment, in established PLP. We considered the following outcomes: change in pain intensity, function, sleep, depression or mood, quality of life, adverse events, treatment satisfaction, and withdrawals from the study. DATA COLLECTION AND ANALYSIS: We independently assessed issues of study quality and extracted efficacy and adverse event data. Due to the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes, but attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results. We assessed clinical heterogeneity by making qualitative comparisons of the populations, interventions, outcomes/outcome measures, and methods. MAIN RESULTS: We added only one new study with 14 participants to this updated review. We included a 14 studies (10 with low risk of bias and 4 with unclear risk of bias overall) with a total of 269 participants. We added another drug class, botulinum neurotoxins (BoNTs), in particular botulinum toxin A (BoNT/A), to the group of medications reviewed previously. Our primary outcome was change in pain intensity. Most studies did not report our secondary outcomes of sleep, depression or mood, quality of life, treatment satisfaction, or withdrawals from the study.BoNT/A did not improve phantom limb pain intensity during the six months of follow-up compared with lidocaine/methylprednisolone.Compared with placebo, morphine (oral and intravenous) was effective in decreasing pain intensity in the short term with reported adverse events being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems.The N-methyl D-aspartate (NMDA) receptor antagonists ketamine (versus placebo; versus calcitonin) and dextromethorphan (versus placebo), but not memantine, had analgesic effects. The adverse events of ketamine were more serious than placebo and calcitonin and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety.The results for gabapentin in terms of pain relief were conflicting, but combining the results favoured treatment group (gabapentin) over control group (placebo) (mean difference -1.16, 95% confidence interval -1.94 to -0.38; 2 studies). However, gabapentin did not improve function, depression score, or sleep quality. Adverse events experienced were somnolence, dizziness, headache, and nausea.Compared with an active control benztropine mesylate, amitriptyline was not effective in PLP, with dry mouth and dizziness as the most frequent adverse events based on one study.The findings for calcitonin (versus placebo; versus ketamine) and local anaesthetics (versus placebo) were variable. Adverse events of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes. AUTHORS' CONCLUSIONS: Since the last version of this review, we identified another study that added another form of medical therapy, BoNTs, specifically BoNT/A, to the list of pharmacologic interventions being reviewed for clinical efficacy in phantom limb pain. However, the results of this study did not substantially change the main conclusions. The short- and long-term effectiveness of BoNT/A, opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anaesthetics for clinically relevant outcomes including pain, function, mood, sleep, quality of life, treatment satisfaction, and adverse events remain unclear. Based on a small study, BoNT/A (versus lidocaine/methylprednisolone) does not decrease phantom limb pain. Morphine, gabapentin, and ketamine demonstrate favourable short-term analgesic efficacy compared with placebo. Memantine and amitriptyline may not be effective for PLP. However, results must be interpreted with caution, as they were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, local anaesthetics, and dextromethorphan needs further clarification. Overall, the efficacy evidence for the reviewed medications is thus far inconclusive. Larger and more rigorous randomised controlled trials are needed for us to reach more definitive conclusions about which medications would be useful for clinical practice.

Pharmacologic interventions for treating phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable and disabling. Various medications have been studied in the treatment of phantom pain. Presently there is uncertainty in the optimal pharmacologic management of PLP.  OBJECTIVES: This review aims to summarize the evidence of effectiveness of pharmacologic interventions in treating PLP. SEARCH METHODS: We searched the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS) Trials Register, the Cochrane Controlled Trials Register (CENTRAL, The Cochrane Library), MEDLINE and EMBASE up to September 2011 for randomised and quasi-randomised trials comparing pharmacologic treatment with placebo, another active treatment, or no treatment. SELECTION CRITERIA: We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions in patients with established PLP. The outcomes considered were change in pain intensity, function, mood, sleep, quality of life, satisfaction and adverse effects. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the methodologic quality of the studies and extracted the data. We reported continuous and dichotomous data on change in pain intensity, function, mood/depression scores, sleep, quality of life, satisfaction for each study, where available. Because of the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes but we attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results and described adverse effects. We assessed clinical heterogeneity by making qualitative comparisons in terms of the populations, interventions, outcomes/outcome measures and methods. MAIN RESULTS: From 583 references/publications, we selected 13 studies involving 255 participants. Six groups of medications were reviewed, namely, N-methyl D-aspartate (NMDA) receptor antagonists, antidepressants, anticonvulsants, anaesthetics, opioids, and calcitonin. Ten studies were of high quality and three were of moderate quality based on both Jadad and Van Tulder criteria. Because of the wide variation (heterogeneity) in the pharmacologic interventions, outcome measures, analyses, reporting of results, duration of follow-ups and study designs, it was not possible to pool the results for most of the interventions and outcomes. Morphine (oral and intravenous) was effective in decreasing pain intensity in the short-term with reported adverse effects being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems. The NMDA receptor antagonists, ketamine and dextromethorphan but not memantine, had analgesic effects. The adverse effects of ketamine were more serious and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety. The results for gabapentin in terms of pain relief were conflicting but combining the results showed a trend towards benefit. Gabapentin, however, did not improve function, depression score and sleep quality. Side effects experienced were somnolence, dizziness, headache and nausea. Amitryptiline was not effective in PLP with dry mouth and dizziness as side effects based on one study. The findings for calcitonin and anaesthetics were variable. Adverse effects of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes. AUTHORS' CONCLUSIONS: The short- and long-term effectiveness of opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and anaesthetics for clinically relevant outcomes that include pain, function, mood, sleep, quality of life, satisfaction and adverse effects remains unclear. Morphine, gabapentin and ketamine demonstrate trends towards short-term analgesic efficacy. Memantine and amitriptyline were ineffective for PLP. Results, however, are to be interpreted with caution as these were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, anaesthetics and dextromethorphan need further clarification. Larger and more rigorous randomised controlled trials are needed to make stronger recommendations about which medications would be useful for clinical practice.

Rehabilitation of urinary incontinence following delayed bladder exstrophy repair in a female child

Bladder exstrophy is relatively rare and even more rarely referred for rehabilitation. A nine-year-old girl with congenital bladder exstrophy from Samar presented with an abnormally low umbilicus, an abdominal opening below the umbilicus, and an anteriorly located anus. The patient has had no prior medical consult. She underwent primary repair of the exstrophy, anterior innominate bone osteotomy, application of external fixators, and traction. Postoperatively, the patient was referred for multidisciplinary rehabilitation management. The rehabilitation bladder program consisted of bladder training with clean intermittent catherization, use of voiding diaries, fluid restriction, timed voiding, electrical stimulation, and pelvic floor muscle exercises. Bed sore care, pulmophysiotherapy, and strengthening exercises for lower extremities were also implemented. At present there are no validated guideline in the management of urinary incontinence among female children with pelvic surgery, specifically with bladder exstrophy. This case report aims to present the rehabilitation management of female pediatric patient with delayed bladder exstrophy repair, resulting in improved outcome.

Vitamin B for treating peripheral neuropathy.

BACKGROUND: Vitamin B is frequently used for treating peripheral neuropathy but its efficacy is not clear. OBJECTIVES: The objective of this review was to assess the effects of vitamin B for treating generalised peripheral neuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (searched August 2005), MEDLINE (January 1966 to September 2005), EMBASE (January 1980 to September 2005), Philippine databases (searched September 2005) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials where vitamin B was compared with placebo or another treatment in generalised peripheral neuropathy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: Thirteen studies involving 741 participants with alcoholic or diabetic neuropathy were included. In the comparison of vitamin B with placebo, two small trials showed no significant short-term benefit in pain intensity while one of the trials showed a small significant benefit in vibration detection from oral benfotiamine, a derivative of thiamine. In the larger of two trials comparing different doses of vitamin B complex, there was some evidence that higher doses resulted in a significant short-term reduction in pain and improvement in paraesthesiae, in a composite outcome combining pain, temperature and vibration, and in a composite outcome combining pain, numbness and paraesthesiae. There was some evidence that vitamin B is less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in the short-term improvement of clinical and nerve conduction study outcomes but the trials were small. There were few minor adverse effects reported. AUTHORS' CONCLUSIONS: There are only limited data in randomised trials testing the efficacy of vitamin B for treating peripheral neuropathy and the evidence is insufficient to determine whether vitamin B is beneficial or harmful. One small trial in alcoholic peripheral neuropathy reported slightly greater improvement in vibration perception threshold with oral benfotiamine for eight weeks than placebo. In another small study, a higher dose of oral vitamin B complex for four weeks was more efficacious than a lower dose in reducing symptoms and signs. Vitamin B administered by various routes for two to eight weeks was less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in short-term improvement of clinical and nerve conduction study outcomes. Vitamin B is generally well-tolerated.