A randomised controlled trial of prophylactic neuroleptic treatment. Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. Continuation ECT in treatment-resistant schizophrenia: a controlled study. Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study. A trial of two cognitive-behavioural methods of treating drug-resistant residual psychotic symptoms in schizophrenic patients: I. Outcome. A trial of neuropsychologic rehabilitation in mild-spectrum traumatic brain injury.
Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness, 120 entered a randomised placebo-controlled trial of maintenance neuroleptic medication on discharge; they were followed to relapse or loss to follow-up, for two years or to the end of the study. Of those on active medication, 46% relapsed, as did 62% of those on placebo; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication. This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis, or because susceptibility to relapse is reduced by early institution of treatment. The study provides no data on which a decision between these alternative explanations can be based. Fibromyalgia has been recognized as a central pain disorder with evidence of neuroanatomic and neurophysiologic alterations. Previous studies with techniques of noninvasive brain stimulation--transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)--have shown that these methods are associated with a significant alleviation of fibromyalgia-associated pain and sleep dysfunction. Here we sought to determine whether a longer treatment protocol involving 10 sessions of 2 mA, 20 min tDCS of the left primary motor (M1) or dorsolateral prefrontal cortex (DLPFC) could offer additional, more long-lasting clinical benefits in the management of pain from fibromyalgia. METHODS: Forty-one women with chronic, medically refractory fibromyalgia were randomized to receive 10 daily sessions of M1, DLPFC, or sham tDCS. RESULTS: Our results show that M1 and DLPFC stimulation both display improvements in pain scores (VAS) and quality of life (FIQ) at the end of the treatment protocol, but only M1 stimulation resulted in long-lasting clinical benefits as assessed at 30 and 60 days after the end of treatment. CONCLUSIONS: This study demonstrates the importance of the duration of the treatment period, suggesting that 10 daily sessions of tDCS result in more long lasting outcomes than only five sessions. Furthermore, this study supports the findings of a similarly designed rTMS trial as both induce pain reductions that are equally long-lasting. Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity. Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity. Because transcranial direct current stimulation (tDCS) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain, we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia.
                Thirty-two patients were randomized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) (2 mA for 20 minutes on 5 consecutive days). A blinded evaluator rated the patient's pain, using the visual analog scale for pain, the clinician's global impression, the patient's global assessment, and the number of tender points. Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form 36 Health Survey. Safety was assessed with a battery of neuropsychological tests. To assess potential confounders, we measured mood and anxiety changes throughout the trial.
                Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC (P < 0.0001). Although this effect decreased after treatment ended, it was still significant after 3 weeks of followup (P = 0.004). A small positive impact on quality of life was observed among patients who received anodal M1 stimulation. This treatment was associated with a few mild adverse events, but the frequency of these events in the active-treatment groups was similar to that in the sham group. Cognitive changes were similar in all 3 treatment groups.
                Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia, thus encouraging further trials. Neuropathic pain in patients with MS is frequent and is associated with a great interference with daily life activities. In the present study, we investigated whether anodal transcranial direct current stimulation (tDCS) may be effective in reducing central chronic pain in MS patients. Patients received sham tDCS or real tDCS in a 5-day period of treatment in a randomized, double blind, sham-controlled study. Pain was measured using visual analog scale (VAS) for pain and the short form McGill questionnaire (SF-MPQ). Quality of life was measured using the Multiple Sclerosis Quality of Life-54 scale (MSQoL-54). Depressive symptoms and anxiety were also evaluated as confounding factors using the Beck Depression Inventory (BDI) and VAS for anxiety. Evaluations were performed at baseline, immediately after the end of treatment, and once a week during a 3-week follow-up period. Following anodal but not sham tDCS over the motor cortex, there was a significant pain improvement as assessed by VAS for pain and McGill questionnaire, and of overall quality of life. No depression or anxiety changes were observed. Our results show that anodal tDCS is able to reduce pain-scale scores in MS patients with central chronic pain and that this effect outlasts the period of stimulation, leading to long-lasting clinical effects.
                This article presents a new, noninvasive therapeutic approach to chronic, central neuropathic pain in multiple sclerosis, poorly responsive to current conventional medications. tDCS is known to cause long-lasting changes of neuronal excitability at the site of stimulation and in the connected areas in healthy subjects. This led us to hypothesize that pain decrease may be the result of functional plastic changes in brain structures involved in the pathogenesis of chronic neuropathic pain.
                Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved. In patients with treatment-resistant schizophrenia (TRS), this study compared the efficacy of continuation treatment with flupenthixol alone, continuation electroconvulsive therapy (ECT) alone, and combined continuation ECT and flupenthixol. One hundred fourteen TRS patients received acute treatment (Phase I) with bilateral ECT and flupenthixol (12-24 mg/day). Fifty-eight patients met remitter criteria, including clinical stability during a 3-week stabilization period, and were eligible for the continuation treatment study (Phase II). Fifty-one patients enrolled in the single-blind Phase II continuation trial, and were randomized to the three treatment groups. The duration of the Phase II study was 6 months. Assessments of outcome included the Brief Psychiatric Rating Scale, Global Assessment of Functioning, and the Mini-Mental State Examination. Forty-five patients either relapsed or completed the Phase II study, and six patients dropped out. Among completers, 6 of 15 (40%) patients relapsed in the combined continuation ECT and flupenthixol group. In both the group treated with continuation ECT alone and that with flupenthixol alone, 14 of 15 (93%) patients relapsed. Analyses of intent-to-treat and completer samples demonstrated a marked advantage for the combination treatment condition in relapse prevention. Furthermore, all eight patients who received maintenance ECT combined with neuroleptic medication (Phase III study) maintained therapeutic benefits during the follow-up period of 3-17 months after the continuation treatment study. Among TRS patients who respond to acute combination treatment with ECT and neuroleptic therapy, continuation of this combination treatment is more effective in relapse prevention than use of ECT or neuroleptic therapy alone. Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation.
                We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS ("tDCS/TENS" group), active tDCS/sham TENS ("tDCS" group), and sham tDCS/sham TENS ("sham" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater.
                The results showed that there was a significant difference in pain reduction across the conditions of stimulation (P=0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/-10.7), P=0.004] and the tDCS condition [reduction by 15.5% (+/-4.9), P=0.014], but not after sham stimulation (P=0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P=0.02).
                The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone. Despite neuroleptic medication, many schizophrenic patients continue to experience residual positive psychotic symptoms. These residual symptoms cause distress and disability. We report a controlled trial of two cognitive-behavioural treatments to alleviate residual hallucinations and delusions. Forty-nine patients were recruited into the trial, of whom 27 entered the trial and completed post-treatment assessment, and 23 were reassessed at six-month follow-up. Patients were randomly allocated to either coping strategy enhancement (CSE) or problem solving (PS). Half the patients were allocated to a high-expectancy positive demand condition and half to a counter-demand condition to evaluate expectation of improvement. Patients receiving either cognitive-behavioural treatment showed significant reductions in psychotic symptoms compared with those in the waiting period, who showed no improvement. There was some evidence, although equivocal, that patients receiving CSE improved more than those receiving PS. There was no evidence that improvements generalised to negative symptoms or social functioning, nor was there evidence that expectancy of treatment benefit contributed to the treatment effect. To test the effectiveness of a neuropsychologic rehabilitation program consisting of psychotherapy and cognitive remediation in the treatment of the affective and neuropsychologic sequelae of mild-spectrum traumatic brain injury (TBI).
                Single-blind randomized, wait-listed controlled trial, with repeated measures and multiple baselines.
                Outpatient clinic in northern New Jersey.
                Twenty persons with persisting complaints after mild and moderate TBI (11 in treatment group, 9 controls).
                The experimental group received both 50 minutes of individual cognitive-behavioral psychotherapy and 50 minutes of individual cognitive remediation, 3 times a week for 11 weeks. The control group was wait-listed and received treatment after conclusion of follow-up.
                Symptom Check List-90R General Symptom Index, plus scales of depression, anxiety, coping, attention, and neuropsychologic functioning.
                Compared with the control group, the treatment group showed significantly improved emotional functioning, including lessened anxiety and depression. Most significant improvements in emotional distress were noted at 1 month and 3 months posttreatment. Performance on a measure of divided auditory attention also improved, but no changes were noted in community integration scores.
                Cognitive behavioral psychotherapy and cognitive remediation appear to diminish psychologic distress and improve cognitive functioning among community-living persons with mild and moderate TBI.
Limited data from small studies using neuroleptic reduction or specific neuroleptic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration in order to fully investigate this area.