Circadian phase in adults of contrasting ages.

There is evidence that aging may impair phase-shifting responses to light synchronizers, which could lead to disturbed or malsynchronized circadian rhythms. To explore this hypothesis, 62 elder participants (age, 58 to 84 years) and 25 young adults (age, 19 to 40 years) were studied, first with baseline 1-wk wrist actigraphy at home and then by 72 h in-laboratory study using an ultra-short sleep-wake cycle. Subjects were awake for 60 minutes in 50 lux followed by 30 minutes of darkness for sleep. Saliva samples were collected for melatonin, and urine samples were collected for aMT6s (a urinary metabolite of melatonin) and free cortisol every 90 minutes. Oral temperatures were also measured every 90 minutes. The timing of the circadian rhythms was not significantly more variable among the elders. The times of lights-out and wake-up at home and urinary free cortisol occurred earlier among elders, but the acrophases (cosinor analysis-derived peak time) of the circadian rhythm of salivary melatonin, urinary aMT6s, and oral temperature were not significantly phase-advanced among elders. The estimated duration of melatonin secretion was 9.9 h among elders and 8.4 h among young adults (p < 0.025), though the estimated half-life of blood melatonin was shorter among elders (p < 0.025), and young adults had higher saliva melatonin and urinary aMT6s levels. In summary, there was no evidence for circadian desynchronization associated with aging, but there was evidence of some rearrangement of the internal phase-angles among the studied circadian rhythms.

Efficacy of a 1- to 3-day ambulatory electroencephalogram in recording epileptic seizures.

The duration of an ambulatory electroencephalogram (aEEG) necessary to record epileptic seizures was studied in neurological patients. A total of 2221 aEEG recordings were made for 2035 inpatients. Ambulatory EEG lasting 1 to 8 days (mean, 1.6 days) included seizures or typical undiagnosed symptomatic attacks in 750 recordings (34%), and 266 of them were epileptic in origin. Symptomatic attacks without simultaneous EEG discharges were exhibited in 27% of the epileptic patients. Of the total number of epileptic seizures, 81% were encountered during the first 24 hours, an additional 10% during the next 24 hours, and 7% during the third 24-hour period. Our conclusion was that, in patients exhibiting epileptic seizures during the aEEG recording, the diagnosis will be confirmed by a 2-day recording in the vast majority of the cases.

Dropout rates in randomised antipsychotic drug trials.

RATIONALE: It has been assumed that new atypical drugs improve treatment compliance due to fewer adverse effects. Data supporting this assumption are scarce. OBJECTIVES: The aim of this study was to study attrition rates in randomised controlled trials of oral administration of conventional antipsychotic drugs, atypical antipsychotic drugs and placebo. METHODS: The database of the Schizophrenia Module of the Cochrane Library was utilised for the present study. The data in the Cochrane Module are collected by identifying relevant randomised controlled trials from several electronic databases and other sources. Number of dropouts was defined as patients leaving the study preterm due to any reason. RESULTS: Data from 328 treatment groups, consisting of 18,585 randomised subjects from 163 drug trials, were entered in the analysis. One-third of the subjects had dropped out of the trials. The dropout rates significantly increased for each calendar year. Year of trial publication, type of drug and trial length remained statistically significant contributors to dropout rates. In a model incorporating year of publication and trial length, placebo groups and groups treated with conventional antipsychotics had significantly higher attrition rates than groups treated with atypical drugs. When clozapine-treated groups were excluded from the analysis, no statistically significant advantage for atypical drugs over conventional drugs remained. CONCLUSIONS: Trial data implicate that a better compliance can be achieved by favouring atypical drugs rather than conventional alternatives in the treatment of schizophrenia. However, this effect is found only when groups treated with the atypical antipsychotic clozapine are included in the analysis. Our study did not find evidence for a statistically significant superiority in acceptability of novel atypical drugs when compared to conventional antipsychotics.

Short version of the CES-D (Burnam screen) for depression in reference to the structured psychiatric interview.

A new screen for depression was compared with clinician diagnoses based on the Structured Clinical Interview for DSM-IV (SCID) as the standard. Post-menopausal women (n=436) completed the Burnam screen, a short version of the Center for Epidemiologic Studies Depression Scale (CES-D). The Burnam screen had a sensitivity of 74% and a specificity of 87% for current major depression and dysthymia, but the positive predictive value was low (20%) and the overall error rate was 14%. For lifetime mood disorders, sensitivity was very low for detecting affected subjects, even though specificity and positive predictive value were higher than for current conditions. Substituting a more sensitive cutpoint slightly improved the screen's ability to detect subjects with lifetime mood disorders. Even algorithms that used coefficients optimized for these data gave little improvement in the psychometric properties of the Burnam screen. These results re-emphasize the difficulty of using a one-stage screen to detect accurately a depressive diagnosis.

Retinal circadian rhythms in humans.

Circadian rhythms in the retina may reflect intrinsic rhythms in the eye. Previous reports on circadian variability in electrophysiological human retinal measures have been scanty, and the results have been somewhat inconsistent. We studied the circadian variation of the electrooculography (EOG), electroretinography (ERG), and visual threshold (VTH) in subjects undergoing a 36h testing period. We used an ultrashort sleep-wake cycle to balance effects of sleep and light-dark across circadian cycles. Twelve healthy volunteers (10 males, 2 females; mean age 26.3 years, standard deviation [SD] 8.0 years, range 19-40 years) participated in the study. The retinal functions and oral temperature were measured every 90 min. The EOG was measured in the light, whereas the ERG and the VTH were measured in the dark. Sleep was inferred from activity detected by an Actillume monitor. The EOG peak-to-peak responses followed a circadian rhythm, with the peak occurring late in the morning (acrophase 12:22). The ERG b-wave implicit time peaked in the early morning (acrophase 06:46). No statistically significant circadian rhythms could be demonstrated in the ERG a-wave implicit time or peak-to-peak amplitude. The VTH rhythm peaked in the early morning (acrophases 07:59 for blue and 07:32 for red stimuli). All retinal rhythms showed less-consistent acrophases than the temperature and sleep rhythms. This study demonstrated several different circadian rhythms in retinal electrophysiological and psychophysical measures of healthy subjects. As the retinal rhythms had much poorer signal-to-noise ratios than the temperature rhythm, these measures cannot be recommended as circadian markers.

Newer atypical antipsychotic medication versus clozapine for schizophrenia.

BACKGROUND: Clozapine is an atypical antipsychotic drug, which is claimed to have superior efficacy and to cause fewer movement disorders. However, clozapine carries a significant risk of serious blood disorders. Newer atypical antipsychotics are safer alternatives that might share the benefits of clozapine. It is thus of interest to compare the effectiveness of newer atypical antipsychotics with the effectiveness of clozapine. OBJECTIVES: To evaluate the clinical effects of newer atypical antipsychotic drugs in comparison to clozapine for schizophrenia. SEARCH STRATEGY: Publications in all languages were searched from the following databases: Biological Abstracts/BIOSIS (1980-1999), The Cochrane Schizophrenia Group's Register of Trials (1998), The Cochrane Library CENTRAL Register (Issue 4, 1999), EMBASE (1980-1998), MEDLINE (1966-1999), LILACS/CD-ROM (1998), and PsycLIT/PsycINFO (1974-1999). Trials were also sought from recent conference proceedings and reference lists of included papers. Authors of recent trials and the manufacturers of clozapine, iloperidone, olanzapine, quetiapine, remoxipride, risperidone, sertindole, ziprasidone and zotepine were contacted. SELECTION CRITERIA: All randomised controlled trials comparing clozapine with newer atypical antipsychotic drugs were included by independent assessment by two reviewers. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Relative risks (RR) and 95% confidence intervals (CI) of homogenous dichotomous data were calculated. A random effects model was used for heterogeneous dichotomous data. Where possible the number needed to treat (NNT) statistic with 95%CI were also calculated. Weighted or standardised means were calculated for continuous data. Due to the small number of included studies, sensitivity analyses or funnel plot statistics were not undertaken for this version of the review. MAIN RESULTS: The current review includes eight studies (22 papers), of which three studies are 4-6 weeks in duration and only one study is of more than 12 weeks' duration. Newer atypical drugs seemed to be broadly similar to clozapine using a clinical global index or trialists' definitions of improvement, but this result was obtained from a relatively small number of studies. Due to the small number of studies and patients, wide confidence intervals were seen when their effectiveness as measured by symptom rating scales was compared. Social functioning was better in patients on newer atypical medication (risperidone) than in those on clozapine, but this finding is based on a single underpowered trial and has to be interpreted with caution. Clozapine and newer atypical drugs showed their adverse effect profile to be dissimilar: while clozapine produced more fatigue, hypersalivation, nausea, and orthostatic dizziness, new atypical drugs, with the exception of olanzapine, produced more extrapyramidal symptoms. The impact of these drugs and their effects on patients' day-to-day quality of life, service use, hospital admission, and pharmacoeconomics was not measured. REVIEWER'S CONCLUSIONS: The equal effectiveness and tolerability of new atypical drugs in comparison with clozapine is not yet demonstrated. Lack of statistical power to determine the comparative efficacy and effectiveness of newer atypical drugs makes it difficult to judge whether newer drugs are more effective, less effective or equivalent. Trials of sufficient power, with longer duration, measuring clinically important outcomes, are needed to assess the true comparative clinical effectiveness, tolerability and cost effectiveness of newer drugs in relation to clozapine.

Light therapy for non-seasonal depression.

BACKGROUND: Efficacy of light therapy for non-seasonal depression has been studied without any consensus on its efficacy. OBJECTIVES: To evaluate clinical effects of bright light therapy in comparison to the inactive placebo treatment for non-seasonal depression. SEARCH STRATEGY: We searched the Depression Anxiety & Neurosis Controlled Trials register (CCDANCTR January 2003), comprising the results of searches of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 -), EMBASE (1980 -), CINAHL (1982 -), LILACS (1982 -), National Research Register, PsycINFO/PsycLIT (1974 -), PSYNDEX (1977 -), and SIGLE (1982 - ) using the group search strategy and the following terms: #30 = phototherapy or ("light therapy" or light-therapy). We also sought trials from conference proceedings and references of included papers, and contacted the first author of each study as well as leading researchers in the field. SELECTION CRITERIA: Randomized controlled trials comparing bright light with inactive placebo treatments for non-seasonal depression. DATA COLLECTION AND ANALYSIS: Data were extracted and quality assessment was made independently by two reviewers. The authors were contacted to obtain additional information. MAIN RESULTS: Twenty studies (49 reports) were included in the review. Most of the studies applied bright light as adjunctive treatment to drug therapy, sleep deprivation, or both. In general, the quality of reporting was poor, and many reviews did not report adverse effects systematically. The treatment response in the bright light group was better than in the control treatment group, but did not reach statistical significance. The result was mainly based on studies of less than 8 days of treatment. The response to bright light was significantly better than to control treatment in high-quality studies (standardized mean difference (SMD) -0.90, 95% confidence interval (CI) -1.50 to -0.31), in studies applying morning light treatment (SMD -0.38, CI -0.62 to -0.14), and in sleep deprivation responders (SMD -1.02, CI -1.60 to -0.45). Hypomania was more common in the bright light group compared to the control treatment group (risk ratio 4.91, CI 1.66 to 14.46, number needed to harm 8, CI 5 to 20). Twenty studies (49 reports) were included in the review. Most of the studies applied bright light as adjunctive treatment to drug therapy, sleep deprivation, or both. Treatment REVIEWERS' CONCLUSIONS: For patients suffering from non-seasonal depression, bright light therapy offers modest though promising antidepressive efficacy, especially when administered during the first week of treatment, in the morning, and as an adjunctive treatment to sleep deprivation responders. Hypomania as a potential adverse effect needs to be considered. Due to limited data and heterogeneity of studies these results need to be interpreted with caution.

Risperidone versus other atypical antipsychotic medication for schizophrenia.

BACKGROUND: Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. OBJECTIVES: To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. SELECTION CRITERIA: All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity. MAIN RESULTS: Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented. REVIEWER'S CONCLUSIONS: The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.

Ictal recordings of ambulatory cassette EEG with sphenoidal electrodes in temporal lobe epilepsy: comparison with intensive videomonitoring.

Seventy-three seizures in 18 epilepsy patients were studied by analyzing the ictal findings of 8-channel ambulatory EEG (A/EEG) and adjacent 16-channel intensive videomonitoring (IVM). With IVM and A/EEG analysis, accuracy was excellent for determining the lateralization of seizure progression; whereas at seizure onset and post-ictal slowing, accuracy was poor. No false lateralization was found in A/EEG compared with IVM or lateralization according to patient data, and in seizure lateralization the interpretation of A/EEG was discordant in only 3 seizures with IVM analysis. According to our study, ictal 8-channel A/EEG with sphenoidal electrodes is not suitable for localization of temporal lobe foci, but is reliable for lateralization analysis.

Postoperative psychoses in epileptic patients after temporal lobectomy.

INTRODUCTION: Psychosis is the most severe psychiatric complication after epilepsy surgery. PATIENTS AND METHODS: We evaluated postoperatively at 1 year the psychoses of a series of 57 adult patients with intractable epilepsy who underwent temporal lobe surgery. RESULTS: Five patients (8.8%) developed postoperative psychosis. Two (3.5%) of these 5 revealed postictal psychotic episodes in connection with persisting seizures, both of them had had similar episodes even preoperatively. Two patients (3.5%) exhibited a definite and one patient (1.8%) a probable de novo schizophrenia. CONCLUSION: Our findings clearly emphasize the need for careful postoperative psychiatric follow-up for patients with temporal lobectomy.

Value of the initial stimulus dose in right unilateral and bifrontal electroconvulsive therapy.

BACKGROUND: The outcome of electroconvulsive therapy (ECT) is affected by the placement and dose of the stimulus. In general, the ECT dose can be selected either by the dose-titration method (on which the measured seizure threshold level is based), or the method of predetermined dose (e.g. the age-based dosing and the fixed high dose method). METHODS: Seizure thresholds were measured in 50 patients with right unilateral (RUL) and in 30 patients with experimental bifrontal (BF) ECT stimulus. The ECT dose (mC) of the age-based dosing was calculated by multiplying the age (years) by 5.0 (age method) or 2.5 (half-age method). The fixed high dose was set to 378 mC. RESULTS: The seizure thresholds had only a moderate correlation with the age of the patients. The methods based on the predetermined dose would have led us to give patients with the lowest seizure thresholds in the RUL ECT group very high stimulus doses, up to 12 (age method) or 15 (fixed high dose method) times the individual seizure threshold. In contrast, the RUL ECT patients with the highest seizure thresholds would have received low stimulus doses down to 1.5 times (half-age method) the initial seizure threshold. In the BF ECT group the-age based dose would have been similarly dependent on the initial seizure threshold level. CONCLUSION: The use of the dose-titration method is recommended, because it is the only method that allows for the individual selection of ECT stimulus dose relative to the seizure threshold.