Anticonvulsant drugs for acute and chronic pain.
Cochrane Database Syst Rev. 2010; CD001133Wiffen PJ, Collins S, McQuay HJ, Carroll D, Jadad A, Moore RABACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. Readers are referred to reviews of carbamazepine and gabapentin in T he Cochrane Library which replace the information on those drugs in this review. Other drugs remain unchanged at present in this review OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of anticonvulsant drugs for pain management in clinical practice . Migraine and headache studies are excluded in this revision. SEARCH STRATEGY: Randomised trials of anticonvulsants in acute, chronic or cancer pain were identified by MEDLINE (1966-1999), EMBASE (1994-1999), SIGLE (1980 to 1999) and the Cochrane Controlled Trials Register (CENTRAL/CCTR) (The Cochrane Library Issue 3, 1999). In addition, 41 medical journals were hand searched. Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: September 1999. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of anticonvulsant drugs in patients, with subjective pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent review authors, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data. MAIN RESULTS: Twenty-three trials of six anticonvulsants were considered eligible (1074 patients).The only placebo-controlled study in acute pain found no analgesic effect of sodium valproate.Three placebo-controlled studies of carbamazepine in trigeminal neuralgia had a combined NNT (95% confidence interval (CI)) for effectiveness of 2.5 (CI 2.0 to 3.4). A single placebo-controlled trial of gabapentin in post-herpetic neuralgia had an NNT of 3.2 (CI 2.4 to 5.0). For diabetic neuropathy NNTs for effectiveness were as follows: (one RCT for each drug) carbamazepine 2.3 (CI 1.6 to 3.8), gabapentin 3.8 (CI 2.4 to 8.7) and phenytoin 2.1 (CI 1.5 to 3.6).Numbers-needed-to-harm (NNHs) were calculated where possible by combining studies for each drug entity irrespective of the condition treated. The results were, for minor harm, carbamazepine 3.7 (CI 2.4 to 7.8), gabapentin 2.5 (CI 2.0 to 3.2), phenytoin 3.2 (CI 2.1 to 6.3). NNHs for major harm were not statistically significant for any drug compared with placebo.Phenytoin had no effect in irritable bowel syndrome, and carbamazepine little effect in post-stroke pain. Clonazepam was effective in one study of temporomandibular joint dysfunction. AUTHORS' CONCLUSIONS: Although anticonvulsants are used widely in chronic pain surprisingly few trials show analgesic effectiveness. Only one study identified considered cancer pain. There is no evidence that anticonvulsants are effective for acute pain. In chronic pain syndromes other than trigeminal neuralgia, anticonvulsants should be withheld until other interventions have been tried. While gabapentin is increasingly being used for neuropathic pain the evidence would suggest that it is not superior to carbamazepine.
Standardizing Emergency Department-based Migraine Research: An Analysis of Commonly Used Clinical Trial Outcome Measures.
Acad Emerg Med. 2010 Jan; 17(1): 72-79Friedman BW, Bijur PE, Lipton RBAbstract Objectives: Although many high-quality migraine clinical trials have been performed in the emergency department (ED) setting, almost as many different primary outcome measures have been used, making data aggregation and meta-analysis difficult. The authors assessed commonly used migraine trial outcomes in two ways. First, the authors examined the association of each commonly used outcome versus the following patient-centered variable: the research subject's wish, when asked 24 hours after investigational medication administration, to receive the same medication the next time they presented to an ED with migraine ("would take again"). This variable was chosen as the criterion standard because it provides a simple, dichotomous, clinically sensible outcome, which allows migraineurs to factor important intangibles of efficacy and adverse effects of treatment into an overall assessment of care. The second part of the analysis assessed how sensitive to true efficacy each outcome measure was by calculating sample size requirements based on results observed in previously conducted clinical trials. Methods: This was a secondary analysis of data previously collected in four ED-based migraine randomized trials performed between 2003 and 2007. In each of these trials, subjects were asked 24 hours after administration of an investigational medication whether or not they would want to receive the same medication the next time they came to the ED with a migraine. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for sex and medication received, were calculated as measures of association between the most commonly used outcome measures and "would take again." The sensitivity of each outcome measure to treatment efficacy was determined by calculating the sample size that would be required to detect a statistically significant result using estimates of that outcome obtained in two clinical trials. Results: Data from 378 subjects were used for this analysis. Adjusted ORs for association of "would take again" and other commonly used primary headache outcomes are as follows: achieving a pain-free state by 2 hours, OR = 3.1 (95% CI = 1.8 to 5.4); sustained pain-free status, OR = 4.5 (95% CI = 1.9 to 11.0); and no need for rescue medication, OR = 3.7 (95% CI = 2.1 to 6.6). An improvement on a standardized 11-point pain scale of >/=33% had an adjusted OR = 5.2 (95% CI = 2.2 to 12.4). The best performing alternate outcome, >/=33% improvement, correctly classified 288 subjects and misclassified 77 subjects when compared to "would take again." At least 33% improvement and pain-free by 2 hours required the smallest sample sizes, while sustained pain-free and "would take again" required many more subjects. Conclusions: "Would take again" was associated with all migraine outcome measures we examined. No individual outcome was more closely associated with "would take again" than any other. Even the best-performing alternate outcome misclassified more than 20% of subjects. However, sample sizes based on "would take again" tended to be larger than other outcome measures. On the basis of these findings and this outcome measure's inherent patient-centered focus, "would take again," included as a secondary outcome in all ED migraine trials, is proposed. ACADEMIC EMERGENCY MEDICINE 2010; 17:72-79 (c) 2010 by the Society for Academic Emergency Medicine.
Symptomatic trigeminal autonomic cephalalgias.
Neurologist. 2009 Nov; 15(6): 305-12Cittadini E, Matharu MSBACKGROUND: The trigeminal autonomic cephalalgias (TACs) are a group of primary headache syndromes characterized by strictly unilateral head pain that occurs in association with ipsilateral cranial autonomic features. The group includes cluster headache, paroxysmal hemicrania, and short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. These syndromes differ in attack duration and frequency as well as the response to therapy. Most of the cases of these syndromes are primary headaches, though numerous symptomatic cases have been described albeit that it is difficult to establish a causal relationship with the underlying pathology in most cases. REVIEW SUMMARY: We reviewed the literature to identify the cases of symptomatic TACs that were likely to be secondary to the reported underlying lesion. We also attempted to identify any clinical features that may be pointers for distinguishing these cases from primary cases and thereby inform the diagnostic workup of these disorders. CONCLUSION: Forty cases of symptomatic TACs were identified. These symptomatic headaches were associated with atypical phenotypes, abnormal examination, and poor treatment response though a significant minority had a typical presentation. A relatively high proportion of all TACs were secondary to pituitary tumors. It is difficult to draw up guidelines for the diagnostic workup required on the basis of this small retrospective case series. It remains unclear whether every TAC patient requires neuroimaging, though if it is considered then magnetic resonance imaging is the preferred modality. In addition, we suggest that all TAC patients should be carefully assessed for pituitary disease related symptoms but further investigations with magnetic resonance imaging of the pituitary gland and pituitary hormonal profile should only be undertaken in patients with atypical features, abnormal examination, or those resistant to the appropriate medical treatment.
Incidence of Intracranial Arterial Dissection in Non-emergency Outpatients Complaining of Headache: Preliminary Investigation with MRI/MRA Examinations.
Acta Neurochir Suppl. 2010; 107: 41-4Manabe H, Yonezawa K, Kato T, Toyama K, Haraguchi K, Ito TPurpose: Headache is recognized as one of the specific signs of intracranial arterial dissection (ICrAD). We clarified the incidence of ICrAD in non-emergency outpatients complaining of headache and the nature of headache observed in case of ICrAD. Patient population and methods: Consecutive non-emergency outpatients coming to the neurological and neurosurgical departments and who underwent MRI and MRA examinations were included in this study. The diagnosis of ICrAD was made when patients met the following two conditions: (1) pearl-and-string sign, pearl sign, or string sign on MRA, and (2) high arterial wall signal on T1 images or intimal flap on T2 images. If possible, cerebral angiography and/or black blood MRI and/or surface-image MRI was also performed in cases meeting these criteria. Results: (1) Headache group (172 patients): severe headache was seen in five patients and headache of sudden onset in three. Arterial dissection was diagnosed in eight patients (4.7%, including seven cases of asymptomatic vertebral dissection and one of basilar dissection). The headache noted in most cases of ICrAD was similar to that experienced in daily life. (2) Non-headache group (201 patients): complaints included vertigo/dizziness in 52 patients, gait disturbance in 28, weakness of the arm or leg in 20, and limb numbness in 18, syncope attack in 14, and others in 69. Arterial dissection was diagnosed in six patients (3.0%, including one case of asymptomatic basilar and two of vertebral artery dissection, symptomatic two vertebral and one basilar dissection). Conclusion: We obtained no evidence of significant difference in the incidence of ICrAD in non-emergency outpatients with (4.7%) and without headache (3.0%). The nature of the headache in the cases of ICrAD was similar to that experienced in daily life. ICrAD with nonspecific headache is more common than previously thought.
[SSRI discontinuation syndrome: incidence and differences on three groups of patients treated with paroxetine]
Riv Psichiatr. 2009 May-Jun; 44(3): 169-75Rusconi AC, Carlone C, Muscillo M, de' FM, Podda L, Piccione MIn recent years, many cases have been published about the appearance of a specific syndrome after the suspension or the sharp reduction in dose of antidepressants. Most of the reports and records relating to the very short half-life SSRI paroxetina. The following work intended to investigate the syndrome, its impact and its correlation with some parameters: age, sex, diagnosis, time of taking and antidepressant drug, therapeutic compliance, suspension and symptoms. The study, lasting approximately 6 months, was conducted with 148 outpatient, all treated with paroxetine.This paper highlights how the discontinuation syndrome is rare in individuals who received antidepressant treatment for short periods, and how it is, rather, much more common in cases of depression NAS, followed by panic attacks, compared with case of major depression. A positive correlation seems to be also with sex (having observed that go more frequently to meet withdrawal symptoms subjects male), and with age, patients being young adults between 35 and 55 years. The symptoms reported were very similar among all patients: headache, dizziness, abdominal pain and perineal, elevated pressure, anxiety, depersonalization and derealization, nightmares. Interestingly, the total absence of symptoms related to the original diagnosis of the disorder. Going to investigate the causal event for the emergence of the discontinuation syndrome, it was possible to divide the cases examined in three categories: independent suspension without medical opinion, suspension accelerated (both conditions due to outpatients) and finally patients that, although they had followed all the guidelines for suspension of the drug, had gone to meet equally symptoms. The syndrome can be prevented reducing very gradually the antidepressant dosage, while if there are symptoms it is indicated to reintroduce the drug and then scale or replance it with a different molecule.
Exploratory randomized clinical study of pagoclone in persistent developmental stuttering: the EXamining Pagoclone for peRsistent dEvelopmental Stuttering Study.
J Clin Psychopharmacol. 2010 Feb; 30(1): 48-56Maguire G, Franklin D, Vatakis NG, Morgenshtern E, Denko T, Yaruss JS, Spotts C, Davis L, Davis A, Fox P, Soni P, Blomgren M, Silverman A, Riley GINTRODUCTION: Stuttering is a speech disorder in which the flow of speech is disrupted by repetitions, prolongation, and blocks of sounds, syllables, or words. No pharmacological treatments are approved for use in stuttering, and the most common form of treatment is speech therapy. This study was designed to assess the safety, tolerability, and effectiveness of pagoclone during 8 weeks of double-blind treatment followed by a 1-year open-label extension in patients who stutter. METHODS: An 8-week, multicenter, parallel-group, 2-arm, randomized (ratio 2:1 pagoclone-placebo), double-blind study with a 1-year open-label extension conducted at 16 US centers, including men and women aged 18 to 65 years who developed stuttering before 8 years of age. Twice-daily dosing with pagoclone (n = 88 patients) or matching placebo (n = 44 patients), with primary and secondary efficacy variables defined a priori, including Stuttering Severity Instrument Version 3 outcomes, clinician global impressions of improvement, and the change in the percentage of syllables stuttered. RESULTS: Pagoclone produced an average 19.4% reduction in percentage of syllables stuttered compared with 5.1% reduction for placebo. During open-label treatment, a 40% reduction in the percent syllables stuttered was observed after 1 year of treatment with pagoclone. The most commonly reported adverse event during double-blind treatment was headache (12.5% pagoclone patients, 6.8% placebo patients). DISCUSSION: Pagoclone was effective in reducing symptoms of stuttering and was well tolerated. In light of its favorable tolerability profile, as well as consistency of effects across multiple efficacy variables, pagoclone may have potential as a pharmacological treatment of stuttering. LIMITATIONS: The main limitation of this study was the adequacy of the number of subjects who participated because this study was conducted as a pilot investigation. Furthermore, as this condition waxes and wanes, the assessment of stuttering within the clinic setting may not be an adequate reflection of the stuttering of the patients within the community.
Health problems among the street children of Dharan municipality.
Kathmandu Univ Med J (KUMJ). 2009 Jul-Sep; 7(27): 272-9Thapa K, Ghatane S, Rimal SPBACKGROUND: The street children, a marginalised and vulnerable population to poor health, have grown all over the world and also in our country. The continuous exposure to harsh environment and nature of their life style threatens their mental, physical, social and spiritual well being. With the increasing number the problem is also growing at an alarming proportion. It is therefore important to have baseline data on their health problems. OBJECTIVES: This study was conducted to identify the physical health problems among the street children of Dharan Municipality, Nepal. MATERIALS AND METHODS: This is a cross sectional descriptive study. Forty eight subjects were included in the study. Research instruments included an interview schedule, physical health examination performa and lab investigations (i.e. blood for haemoglobin, urine routine examination/microscopic examination, stool routine examination/ microscopic examination). RESULTS: Study results showed that 68.8% of the street children were between 11-15 years of age, 95.8% were males. Out of the total subjects 81.2% were found to be rag pickers. Research findings reveal that 100% of the subjects had at least one or more health problems. The study revealed that majority 87.5% had the habit of cigarette smoking, 50% had habit of consuming alcohol and 72.9% had the habit of taking drug. Dendrite (glue sniffing) was the only drug used by the respondents in this study. The most common health problems were head lice infestation (81.2%), headache (66.7%), cut injury (60.4%), common cold (52.1%), dental caries (52%), burning micturation (47.9%), cough (47.9%), underweight (43.8%), abdominal pain (39.6%), tinnitus (37.55%), gum bleeding (33.3%), joint pain (31.2%), eye inflammation (25%), leg cramps (25%), palpable lymph nodes (25%), chest pain (18.8%), skin lesions (16.7%), abnormal vision (8.3%). CONCLUSION: Most of the diseases were due to poor health habits. It was found that the nature of work, their life styles and the different types of behaviour they adapt finally lead them to many health problems. The health problem can be prevented, if an integrated program that involves all the issues are developed and implemented.