R G Purvis

Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: A randomized controlled pilot study

BACKGROUND Negative symptoms in schizophrenia are associated with deficits in executive function and frequently prove highly resistant to neuroleptic medication. Using repetitive transcranial magnetic stimulation (rTMS) to activate the prefrontal cortex has been suggested as a treatment for negative symptoms. METHODS We performed a double-blind randomized controlled pilot study of real versus sham rTMS for negative symptoms in schizophrenia. 17 right-handed patients with prominent negative symptoms (PANSS negative subscore >or=20) were randomized to a 10 day course of real (n=8) or sham rTMS (n=9) applied to the left dorsolateral prefrontal cortex (20 trains per day, 10 s treatment at 10 Hz, 50 s inter-train interval, 110% of motor threshold). The primary outcome measure was PANSS negative symptom score. Secondary outcomes included mood, cognitive function and side-effects. Patients were followed-up two weeks afterwards. The main effect of treatment arm was evaluated across end of treatment and two-week follow-up time points using ANCOVA. RESULTS All subjects completed the treatment course. There was no significant difference between the two groups on PANSS negative symptom scores at either time point. At the end of treatment, no subjects in either group met the criterion for response (i.e. a 20% reduction in baseline PANSS negative symptom score). The real rTMS group had better delayed recall on a test of verbal learning than the sham group at 2 week follow-up. CONCLUSIONS Real rTMS was not found to be better than sham rTMS in alleviating negative symptoms of schizophrenia although it was associated with some improvement in aspects of cognitive function at follow-up.

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression.

BACKGROUND Effectiveness of repetitive transcranial magnetic stimulation (rTMS) for major depression is unclear. The authors performed a randomized controlled trial comparing real and sham adjunctive rTMS with 4-month follow-up. METHOD Fifty-nine patients with major depression were randomly assigned to a 10-day course of either real (n=29) or sham (n=30) rTMS of the left dorsolateral prefrontal cortex (DLPFC). Primary outcome measures were the 17-item Hamilton Depression Rating Scale (HAMD) and proportions of patients meeting criteria for response (50% reduction in HAMD) and remission (HAMD8) after treatment. Secondary outcomes included mood self-ratings on Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. Patients had 6-week and 4-month follow-ups. RESULTS Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant groupxtime interaction (p=0.09) or group main effect (p=0.85); the mean difference in HAMD change scores was -0.3 (95% CI -3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06); 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2); the mean difference in HAMD change scores was 2.9 (95% CI -0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters. CONCLUSIONS Adjunctive rTMS of the left DLPFC could not be shown to be more effective than sham rTMS for treating depression.

Cortical effects of quetiapine in first-episode schizophrenia: a preliminary functional magnetic resonance imaging study.

BACKGROUND Quetiapine improves both psychotic symptoms and cognitive function in schizophrenia. The neural basis of these actions is poorly understood. METHODS Three subject groups underwent a single functional magnetic resonance imaging (fMRI) session: drug-naive (n = 7) and quetiapine-treated samples of patients with schizophrenia (n = 8) and a healthy control group (n = 8). The fMRI session included an overt verbal fluency task and a passive auditory stimulation task. RESULTS In the verbal fluency task, there was significantly increased activation in the left inferior frontal cortex in the quetiapine-treated patients and the healthy control sample compared with the drug-naive sample. During auditory stimulation, the healthy control group and stably treated group produced significantly greater activation in the superior temporal gyrus than the drug-naive sample. CONCLUSIONS Quetiapine treatment is associated with altered blood oxygen level-dependent responses in both the prefrontal and temporal cortex that cannot be accounted for by improved task performance subsequent to drug treatment.

Cost-effectiveness of transcranial magnetic stimulation vs. electroconvulsive therapy for severe depression: A multi-centre randomised controlled trial

BACKGROUND Electroconvulsive therapy (ECT) has a long history of use in treating depression. Repetitive transcranial magnetic stimulation (rTMS) has been introduced more recently to the treatment spectrum. Its cost-effectiveness has not been explored. METHOD Forty-six right-handed people with severe depressive episodes referred for ECT were randomised to receive either ECT twice weekly or rTMS on consecutive weekdays. Health and other service use were recorded for retrospective periods of 3 months prior to initiation of treatment and during the 6 months following the end of allocated treatment. Costs were calculated for the treatment period and the subsequent 6 months, and comparisons made between groups after adjustment for any baseline differences. Cost-effectiveness analysis was conducted with incremental change on the 17-item Hamilton Rating Scale for Depression (HRSD) as the primary outcome measure, and quality-adjusted life years (based on SF6D-generated utility scores with societal weights) as secondary outcome, cost-effectiveness acceptability curves plotted. RESULTS Based on the HRSD scores and other outcome measures, rTMS was not as effective as ECT. The cost of a single session of rTMS was lower than the cost of a session of ECT, but overall there were no treatment cost differences. In the treatment and 6-month follow-up periods combined, health and other service costs were not significantly different between the two groups. Informal care costs were higher for the rTMS group. Total treatment, service and informal care costs were also higher for the rTMS group. The cost-effectiveness acceptability curves indicated a very small probability that decision-makers would view rTMS as more cost-effective than ECT. LIMITATIONS Small sample size, some sample attrition and a relatively short follow-up period of 6 months for a chronic illness. Productivity losses could not be calculated. CONCLUSIONS ECT is more cost-effective than rTMS in the treatment of severe depression.

Clinical effectiveness in first-episode patients

Managing patients with first-episode schizophrenia is a challenging task for psychiatrists. Early diagnosis and effective intervention are vital to achieving long-term positive clinical outcomes among first-episode patients. Although these patients are the most responsive to treatment, they are also more susceptible to adverse events. The efficacy and improved tolerability associated with the newer atypical antipsychotics means that these drugs can be used successfully in the treatment and long-term management of schizophrenia from the onset of illness. However, as well as managing the symptoms of the disease, pharmacological treatments need to meet the broader requirements of clinical effectiveness that encompass all of the outcome domains associated with schizophrenia. This article will discuss available data on atypical antipsychotics in first-episode patients and present the primary results from the F1RST (Southwark first-onset psychosis) study, which examined the use of quetiapine for the first-line management of schizophrenia as part of a specialist episode psychosis service.

Is first best? A preliminary study of the effectiveness of the southwark first episode psychosis team (first) versus standard care

charged from a state hospital. Not surprisingly, the concordance among measures of adherence is quite poor. While the more objective measures (e.g. pill counts, blood levels) may be considered by some to have greater validity than the more subjective measures (e.g. self-report), each method has significant advantages and major drawbacks that must considered when designing studies to examine treatment effects. While the use of conventional depot neuroleptics may improve both the ease and accuracy of adherence assessment, the side-effect profiles of these older medications make them an unattractive option for many patients. Supported by NIMH RO1 MH 62850