Effects of using dexamethasone and placebo in the treatment of prolapsed lumbar disc

Previous reports concerning the treatment of symptoms deriving from prolapsed lumbar disc with systemic administration of the potent steroid dexamethasone, have shown favourable results. The present clinical study includes 39 patients with symptoms of prolapsed lumbar disc, treated in a controlled double-blind investigation with dexamethasone or placebo. Twenty patients had provable effect of the treatment, 19 had no effect. Nineteen patients received dexamethasone (13 + effect), 20 received placebo (7 + effect). The groups were fully comparable, and the difference is not statistically significant. During a period of 3 months 50 % of the patients who improved by the treatment in either group had recurrences leading to operation. It is concluded that the effect of dexamethasone given intramuscularly does not seem to exceed that of placebo in the treatment of prolapsed lumbar disc.     

A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder.

BACKGROUND: The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD. METHODS: Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated. RESULTS: Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated. CONCLUSIONS: Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials.     

Assessment: use of epidural steroid injections to treat radicular lumbosacral pain: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Based on the available evidence, the Therapeutics and Technology Assessment subcommittee concluded that 1) epidural steroid injections may result in some improvement in radicular lumbosacral pain when assessed between 2 and 6 weeks following the injection, compared to control treatments (Level C, Class I-III evidence). The average magnitude of effect is small and generalizability of the observation is limited by the small number of studies, highly selected patient populations, few techniques and doses, and variable comparison treatments; 2) in general, epidural steroid injection for radicular lumbosacral pain does not impact average impairment of function, need for surgery, or provide long-term pain relief beyond 3 months. Their routine use for these indications is not recommended (Level B, Class I-III evidence); 3) there is insufficient evidence to make any recommendation for the use of epidural steroid injections to treat radicular cervical pain (Level U).     

Diagnostic value of history, physical examination and needle electromyography in diagnosing lumbosacral radiculopathy

To examine the diagnostic value of history, physical examination and needle EMG in predicting nerve root compression on MRI in patients with clinical suspicion of lumbosacral radicular syndrome (LSRS). Subjects comprised 202 consecutive patients from January 2006 to March 2007 with suspicion of LSRS referred by general practitioners. Clinical evaluation consisted of history, physical examination, EMG and MRI. Bivariate and multiple logistic regression analyses were used to calculate the diagnostic value of each test item compared to radiological nerve root compression. 95 patients (47%) had radiological nerve root compression. Significant predictors of radiological nerve root compression were dermatomal radiation [odds ratio (OR) 2.1], more pain on coughing, sneezing or straining (OR 2.4), positive straight leg raising (OR 3.0) and ongoing denervation on EMG (OR 4.5). 15 patients (7%) had ongoing denervation on EMG without radiological nerve root compression. In clinical practice, dermatomal radiation, more pain on coughing, sneezing or straining, positive straight leg raising and ongoing denervation on EMG may be used to predict nerve root compression on MRI. EMG may also be of additional value in patient with clinical suspicion of lumbosacral radicular syndrome without nerve root involvement on MRI.     

Clinicopathological considerations in patients with lumbosacral extraforaminal stenosis

Lumbosacral extraforaminal stenosis is not uncommon among patients being treated for radicular symptoms. Patients who had lumbosacral extraforaminal stenosis were reviewed, and cadaver dissection was used to determine the anatomy of extraforaminal lesions. A total of 167 patients with lumbosacral spinal stenosis who underwent surgery from March 2004 to February 2006 were reviewed retrospectively. Among these, extraforaminal stenosis was observed in 26 patients (mean age 61.4 y; range 46–79). Leg pain and neurogenic claudication were common in patients with extraforaminal stenosis. One level was involved for 15 patients and 2 levels were involved for 11 patients. Complete decompression of the dorsal root ganglion or a root compressed by the fibrocartilagenous ligamentum flavum or a hypertrophied superior facet was performed. The mean follow-up was 8.3 months (range 6–26 months). The causes of extraforaminal stenosis were superior facet hypertrophy, especially hypertrophy of the superior lateral portion, or thickening of the ligamentum flavum, intertransverse ligament, or transforaminal ligament. T1-weighted, coronal MRI showed root impingement in the far-lateral zone. Postoperative outcomes were assessed using the Prolo scale; 13 patients demonstrated excellent outcomes, while 11 patients had good outcomes. No major complications or recurrences were observed during follow-up. Therefore, lumbosacral extraforaminal stenosis should be included in the differential diagnosis of lumbar radicular pain. A precise diagnosis using MRI is important, and complete decompression with an understanding of the extraforaminal anatomy is required.     

脉冲射频治疗腰骶部神经根性疼痛的疗效观察

目的观察腰骶部背根神经脉冲射频治疗神经根性腰腿痛的临床疗效.方法回顾性研究了68例经保守治疗无效的神经根性腰腿痛病人,在影像学引导下进行穿刺定位,再行背根神经脉冲射频治疗.在病人治疗前及治疗后2个月进行活动时视觉模拟尺度评分(VAS).结果随访2个月后活动时VAS改善≥75%者20例(29.4%);VAS改善≥50%～70)例(42.6%);VAS改善＜50例(28.0%).脉冲射频治疗后无严重并发症发生.结论腰骶部背根神经脉冲射频对神经根性疼痛有治疗作用.     

Escitalopram continuation treatment prevents relapse of depressive episodes

BACKGROUND: Current guidelines for antidepressant use recommend 4 to 6 months of continuation treatment to prevent relapse of depression following symptom resolution. This study evaluates the efficacy and safety of continuation escitalopram treatment. METHOD: Outpatients diagnosed with DSM-IV major depressive disorder (male or female, aged 18 to 81 years) who had completed 8 weeks of randomized double-blind treatment with escitalopram, citalopram, or placebo entered an 8-week flexible-dose, open-label phase in which all patients received escitalopram (10-20 mg/day). This study was initiated November 3, 1999, and completed April 5, 2001. Patients who met responder criteria (score of < or = 12 on the Montgomery-Asberg Depression Rating Scale [MADRS]) were randomly assigned in a 2:1 ratio to escitalopram (at the dose each patient was receiving at the end of the open-label phase) or placebo for 36 weeks of double-blind treatment. The primary efficacy variable was time to depression relapse (defined as MADRS score > or = 22 or discontinuation due to an insufficient therapeutic response) from the start of the double-blind treatment phase. RESULTS: A total of 502 patients received open-label escitalopram treatment and had at least 1 MADRS assessment. A total of 274 evaluable subjects entered the double-blind treatment phase; 93 received placebo and 181 received escitalopram. Time to depression relapse was significantly longer (p =.013) and the cumulative rate of relapse was significantly lower in patients who received escitalopram (26% escitalopram vs. 40% placebo; hazard ratio = 0.56; p =.01). Escitalopram-treated subjects had significantly lower depression ratings than those of placebo-treated patients. Escitalopram continuation treatment was safe and well tolerated. Discontinuation rates due to adverse events were 7% for the placebo group and 4% for the escitalopram-treated group. CONCLUSION: Continuation treatment with escitalopram is effective in preventing relapse into an episode of major depressive disorder.     

Placebo response in panic disorder

Of 43 patients with panic disorder or agoraphobia with panic attacks who took placebo for 8 weeks in two double-blind studies, one in four markedly improved. Those with consistently normal dexamethasone suppression test results were significantly more likely to show a placebo response as were those with lower anxiety ratings at the outset of treatment.     

A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.

OBJECTIVE: This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). METHOD: Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. RESULTS: Thirty-four medication-free subjects (31 boys and three girls with a mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, guanfacine was associated with a mean improvement of 37% in the total score on the teacher-rated ADHD Rating Scale, compared to 8% improvement for placebo. Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved, compared with none of 17 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 27% in the guanfacine group and 21% in the placebo group, not a significant difference. On the Continuous Performance Test, commission errors decreased by 22% and omission errors by 17% in the guanfacine group, compared with increases of 29% in commission errors and of 31% in omission errors in the placebo group. Tic severity decreased by 31% in the guanfacine group, compared to 0% in the placebo group. One guanfacine subject with sedation withdrew at week 4. Guanfacine was associated with insignificant decreases in blood pressure and pulse. CONCLUSIONS: Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.     

Acute radicular pain as a presenting symptom in multiple sclerosis.

From December 1973 through November 1988, we cared for 11 patients who presented with acute radicular pain and in whom radicular compression was ruled out by imaging techniques. Eventually, multiple sclerosis was diagnosed and judged to be responsible for the acute radiculopathy. The patients (seven women, aged 18 to 40 years; median, 32 years) and four men (aged 23 to 34 years; median, 29 years) were followed up from 6 months to 15 years (mean, 4 years 11 months). They represent 3.9% of 282 newly diagnosed cases of multiple sclerosis during the same 15 years. A retrospective analysis of the characteristics of their illness and its evolution was conducted. Six had lumbosacral radiculopathies; three, cervical and two, thoracic. In six of the 11 patients, symptoms occurred in close relationship to trauma; seven had recurrent radicular pain; four had other pain syndromes; and three others, paroxysmal symptoms. One patient died of complications from multiple sclerosis 3 years after diagnosis. Three others were rated five or greater in the extended Kurtzke disability status scale during follow-up.     

Mood-stabilizer-maintained, remitted bipolar patients: taper and discontinuation of adjunctive antipsychotic medication

The aim of this study was to determine whether bipolar patients who had been stabilized on combined antipsychotic and mood-stabilizer medications and were currently in remission benefited from continuation of the antipsychotic medication. Remitted bipolar patients were randomly assigned to either remain on adjunctive antipsychotic medication or to taper to placebo. Antipsychotic/placebo medication assignment was double-blind. Subjects were outpatients at a university-affiliated community mental health center. Fifteen subjects consented and proceeded with eligibility assessments. Five subjects were never randomized. One of these was excluded when the Structured Clinical Interview for DSM-IV interview revealed schizoaffective disorder. The remaining four subjects were not randomized for other reasons. Three randomized subjects never received study medications, or were withdrawn by the investigator within 1 week after beginning study medications. The seven remaining subjects received study medication for more than 1 week. Five subjects were randomized to taper to placebo and two to antipsychotic continuation. Of the five randomized to taper to placebo, three successfully tapered and completed the year of follow-up in continuous remission. One subject became manic 4 months after taper was completed, and one subject became psychotic, in the absence of a mood episode, during taper. Of the two subjects randomized to double-blind antipsychotic continuation, both completed the year of follow-up in continuous remission. When adjunctive antipsychotic medications are discontinued, bipolar patients' clinical symptoms can remain unchanged. Others are, however, at risk for manic relapse.     

Development of depression during placebo-controlled trials of bupropion for smoking cessation: case reports.

BACKGROUND: Recent attention has focused on the relationship between depression and smoking cessation. This article describes 5 cases of severe depression that occurred during 2 multicenter trials using bupropion for smoking cessation. METHOD: Subjects were participants in 2 randomized, double-blind, placebo-controlled studies investigating the efficacy of bupropion for smoking cessation. Data from both trials were restricted to subjects at the Rochester, Minn., site in order to have access to the medical records for information on depression diagnosis, treatment, and follow-up. The first trial involved 205 smokers who received active bupropion or placebo for 7 weeks. In the second trial, 252 smokers received open-label bupropion therapy for 7 weeks. Those abstinent from smoking at the end of week 7 (N = 148) were randomly assigned to a 45-week, double-blind, relapse-prevention phase. RESULTS: In the first trial, 1 of the 205 participants (0.49%) experienced major depression during the 7-week treatment phase. In the second trial, none of the 252 subjects developed major depression during the 7-week, open-label phase. When results of both trials across the 7-week treatment phase (study 1, N = 205; study 2, N = 252) are combined, the rate of developing major depression was 0.22% (1 of 457). Of the 457 subjects, none of the 51 who received placebo and 1 (0.25%) of the 406 who received active bupropion developed major depression. In the second trial, 4 (2.7%) of the 148 subjects randomly assigned to the 45-week, relapse-prevention phase developed depression. Overall, 4 of the 5 cases from the 2 trials had a past history of major depression prior to study entry, but none had current major depression. CONCLUSION: Major depression may occur in some individuals during smoking cessation treatment with bupropion.     

Perceived treatment group affects behavioral and neural responses to visceral pain in a deceptive placebo study

Background To assess effects of perceived treatment (i.e. drug vs placebo) on behavioral and neural responses to rectal pain stimuli delivered in a deceptive placebo condition. Methods This fMRI study analyzed the behavioral and neural responses during expectation‐mediated placebo analgesia in a rectal pain model. In N = 36 healthy subjects, the blood oxygen level‐dependent (BOLD) response during cued anticipation and painful stimulation was measured after participants were informed that they had a 50% chance of receiving either a potent analgesic drug or an inert substance (i.e., double‐blind administration). In reality, all received placebo. We compared responses in subjects who retrospectively indicated that they received the drug and those who believed to have received placebo. Key Results 55.6% (N = 20) of subjects believed that they had received a placebo, whereas 36.1% (N = 13) believed that they had received a potent analgesic drug. Subjects who were uncertain (8.3%, N = 3) were excluded. Rectal pain‐induced discomfort was significantly lower in the perceived drug treatment group (P < 0.05), along with significantly reduced activation of the insular, the posterior and anterior cingulate cortices during pain anticipation, and of the anterior cingulate cortex during pain (all P < 0.05 in regions‐of‐interest analyses). Conclusions & Inferences Perceived treatment constitutes an important aspect in placebo analgesia. A more refined understanding of individual treatment expectations and perceived treatment allocation has multiple implications for the design and interpretation of clinical trials and experimental studies on placebo and nocebo effects.     

A randomized double-blind trial of paroxetine and/or dextroamphetamine and problem-focused therapy for attention-deficit/hyperactivity disorder in adults

OBJECTIVE: To determine the effect of psychotherapy, dextroamphetamine, and/or paroxetine on attention-deficit/hyperactivity-disorder (ADHD) in adults. METHOD: Ninety-eight adults with DSM-IV ADHD were randomly assigned to receive psychotherapy and dextroamphetamine, paroxetine, both, or placebo for 20 weeks. A 2 x 2 factorial design compared patients who received dextroamphetamine versus no dextroamphetamine with patients who received paroxetine versus no paroxetine. Data were collected from August 2000 until May 2002. RESULTS: One half of the 98 enrolled subjects were found to have at least 1 lifetime mood or anxiety disorder on the Structured Clinical Interview for DSM-IV. Sixty percent of patients who received medication and 80% of those who received placebo completed the 5-month trial. ADHD symptoms were significantly (p = .012) lower in patients in the completer group who received dextroamphetamine. Paroxetine had no effect on ADHD. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) scores were low to start, and no treatment differences were evident at endpoint. Significantly (p < .001) more patients in the completer group were rated by clinicians as ADHD responders if they received dextroamphetamine (85.7%) or combined treatment (66.7%) versus paroxetine (20.0%) or placebo (21.1%). Significantly (p = .003) more patients in the completer group were rated by clinicians as mood/anxiety responders if they received paroxetine (100%) or combined treatment (73.3%) versus those receiving dextroamphetamine (57.15%) or placebo (47.4%). Clinicians rated any patient who received medication and psychological therapy as significantly more improved overall than those who received placebo and psychological therapy (intent to treat: p = .033; completers: p = .001). CONCLUSION: ADHD symptoms improved with dextroamphetamine. Mood and internalizing symptoms were seen as improved with paroxetine by clinicians, despite absence of response on the HAM-A and HAM-D. The presence of a lifetime internalizing disorder attenuated the response to dextroamphetamine. Patients who received both dextroamphetamine and paroxetine had more severe adverse events but did not show greater improvement overall than patients treated with 1 medication. Clinical Trials Registry #GSK707.     

The natural history of lumbosacral plexopathy in cancer

We studied 85 cancer patients with lumbosacral plexopathy and documented pelvic tumor by CT or biopsy. Three clinical syndromes were delineated: lower (L4-S1), 51%; upper (L1-L4), 31%; and pan-plexopathy (L1-S3), 18%. Seventy percent of patients had the insidious onset of pelvic or radicular leg pain, followed weeks to months later by sensory symptoms and weakness. The quintet of leg pain, weakness, edema, rectal mass, and hydronephrosis suggests plexopathy due to cancer. CT showed pelvic tumor in 96%. On myelography, epidural extension, usually below the conus medullaris, was seen in 45%. With treatment, only 28% of patients had objective responses on CT and 17% on examination.     

Disturbances of C-fibre-mediated sensibility in lumbosacral disc disease.

In nine patients with chronic lumbosacral disc disease and radicular symptoms clearly restricted to one leg, C-fibre-mediated sensibility was measured by determination of the thresholds for heat pain and warmth on the foot, ipsi- and contralaterally to the nerve root compression. The thresholds were compared with the values for 19 healthy subjects. In the patients the warmth threshold was increased in the ipsilateral dermatome and normal in the contralateral dermatome. In contrast, the heat pain threshold was near normal ipsilaterally but was clearly decreased contralaterally. These findings are discussed with respect to a possible pain sensitisation resulting from nerve root compression.     

Cervicobrachial involvement in diabetic radiculoplexopathy

Diabetic radiculoplexopathy is commonly viewed as a condition affecting the lower extremities. However, other regions may also be affected and the presence of upper extremity involvement has rarely been emphasized. Our goal was to illustrate the clinical features of arm involvement in this condition. Of 60 patients with diabetic lumbosacral radiculoplexopathy, we identified 9 who also had upper extremity involvement. The study included 8 men and 1 woman, ranging in age from 36 to 71 years. Upper limb involvement developed simultaneously with the onset of lower limb disorder in 1 patient, preceded it by 2 months in another patient, and occurred between 3 weeks and 15 months later in the remaining 7. In 5 cases, arm involvement developed after symptoms in the legs began to improve. The upper extremity weakness affected the hands and forearms most severely. It was unilateral in 5 patients and bilateral but asymmetric in 4. Pain was often present, but it was not a prominent feature. In most patients, neurologic deficits in the arms improved spontaneously after 2-9 months. We conclude that diabetic radiculoplexopathy may involve the cervical region before, after, or simultaneously with the lumbosacral syndrome. The upper limb process is similar to that in the legs, with subacutely progressive weakness and pain followed by spontaneous recovery.     

Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling

OBJECTIVE: Pathological gambling is a disabling disorder experienced by approximately 1%-2% of adults and for which there are few empirically validated treatments. The authors examined the efficacy and tolerability of the opioid antagonist nalmefene in the treatment of adults with pathological gambling. METHOD: A 16-week, randomized, dose-ranging, double-blind, placebo-controlled trial was conducted at 15 outpatient treatment centers across the United States between March 2002 and April 2003. Two hundred seven persons with DSM-IV pathological gambling were randomly assigned to receive nalmefene (25 mg/day, 50 mg/day, or 100 mg/day) or placebo. Scores on the primary outcome measure (Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling) were analyzed by using a linear mixed-effects model. RESULTS: Estimated regression coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had significantly different scores on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling, compared to the placebo group. A total of 59.2% of the subjects who received 25 mg/day of nalmefene were rated as "much improved" or "very much improved" at the last evaluation, compared to 34.0% of those who received placebo. Adverse experiences included nausea, dizziness, and insomnia. CONCLUSIONS: Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) appeared efficacious and was associated with few adverse events. Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects.     

Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies.

This report presents the results of a retrospective analysis of pooled efficacy data from eight studies in which buspirone was compared to placebo in 520 patients with generalized anxiety disorder (GAD). In addition to evaluating overall efficacy in the composite patient data base, four criteria were used to identify subsets of patients with GAD who had coexisting depressive symptoms of at least moderate intensity: (1) a score of > or = 2 on the Hamilton Anxiety (HAM-A) Rating Scale item 6 (depressed mood), (2) a score of > or = 2 on the Hamilton Depression (HAM-D) Rating Scale item 1 (depressed mood), (3) a HAM-D total score of > or = 18, or (4) a HAM-D Retardation Factor value (items 1, 7, 8, and 14) greater than the median for the group. Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM-A scores compared to patients who received placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician. Of the GAD patients stratified according to the four criteria for coexisting depressive symptoms, a substantial percentage (44-64%) of the total patient sample exhibited significant depressive symptoms as part of their anxiety disorder. Patients with GAD and coexisting depressive symptoms of at least moderate intensity exhibited significantly greater improvement with buspirone compared to placebo treatment regardless of the stratification criterion used. They also responded at least as well or better to buspirone therapy as did those with GAD who had less intense depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of glucocorticoids on declarative memory function in major depression.

BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD.