P. Sos

The change of prefrontal QEEG theta cordance as a predictor of response to bupropion treatment in patients who had failed to respond to previous antidepressant treatments

UNLABELLED The aim of the study was to examine whether the reduction of theta prefrontal quantitative EEG (QEEG) cordance after one week of bupropion administration is a predictor of response to a 4-week treatment in patients that had failed to respond to previous antidepressant treatments. METHOD EEG data of 18 inpatients were monitored at baseline and after one week. QEEG cordance was computed at 3 frontal electrodes (Fp1, Fp2, Fz). Response to treatment was defined as a >/=50% reduction of MADRS score. RESULTS Nine of the eleven responders and one of the seven non-responders showed decreased prefrontal cordance value after the first week of treatment (p=0.01). Positive and negative predictive values of cordance reduction for the prediction of response to the treatment were 0.9 and 0.75, respectively. CONCLUSION Similar to other antidepressants, the reduction of prefrontal QEEG cordance might be helpful in the prediction of the acute outcome of bupropion treatment.

Electroencephalographic Spectral and Coherence Analysis of Ketamine in Rats: Correlation with Behavioral Effects and Pharmacokinetics

Aims: This study was designed to evaluate the changes in EEG power spectra and EEG coherence in a ketamine model of psychosis in rats. Analyses of behavioral measurements – locomotion and sensorimotor gating – and the pharmacokinetics of ketamine and norketamine were also conducted. Methods: Ketamine and norketamine levels in rat sera and brains were analyzed by gas chromatography-mass spectrometry after ketamine 30 mg/kg (i.p.). Ketamine 9 and 30 mg/kg (i.p.) were used in the behavioral and EEG experiments. Locomotor effects in an open field test and deficits in prepulse inhibition of acoustic startle reaction (PPI ASR) were evaluated in the behavioral experiments. EEG signals were simultaneously recorded from 12 implanted active electrodes; subsequently, an EEG power spectral and coherence analysis was performed. Results: Ketamine had a rapid penetration into the brain; the peak concentrations of the drug were reached within 15 min after administration. Ketamine induced marked hyperlocomotion and deficits in the PPI ASR. EEG spectral analysis mainly showed increases in EEG power as well as coherence. These were most robust at 10–15 min after the administration and influenced all parts of the spectrum with ketamine 30 mg/kg. Conclusions: Ketamine at behaviorally active doses induces a robust increase in EEG power spectra and coherence. The maximum levels of change correlated with the kinetics of ketamine.

Low frequency (1-Hz), right prefrontal repetitive transcranial magnetic stimulation (rTMS) compared with venlafaxine ER in the treatment of resistant depression: a double-blind, single-centre, randomized study.

BACKGROUND Previous studies have shown effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. This double-blind study compared efficacy of l Hz rTMS over the right prefrontal dorsolateral cortex with venlafaxine ER in the treatment of resistant depression. METHODS A total of 60 inpatients with depressive disorder (DSM-IV criteria), who previously did not respond to at least one antidepressant treatment, were randomly assigned to 1 Hz rTMS with placebo and venlafaxine ER with sham rTMS for 4 weeks. The primary outcome measure was score change in the Montgomery-Asberg Depression Rating Scale (MADRS). We also used Clinical Global Impression (CGI) and Beck Depressive. Inventory-Short Form (BDI-SF). The response was defined as a >or=50% reduction of MADRS score. RESULTS There were no significant differences between treatment groups in MADRS (p=0.38), BDI-SF (p=0.56) and CGI (p=0.17) scores from baseline to endpoint. Response rates for rTMS (33%) and venlafaxine (39%) as well as remission (MADRS score<or=10 points) rates (19% vs. 23%) and drop-out rate did not differ between treatment groups. There were significant reductions of MADRS, CGI and BDI-SF scores in both groups. LIMITATIONS Small sample size. No placebo arm was included for ethical reasons, because both treatments have previously been reported to be more effective than placebo. Relatively short duration of antidepressant treatment. CONCLUSION The findings of this study suggest that, at least in the acute treatment, the right sided rTMS produces clinically relevant reduction of depressive symptomatology in patients with resistant depression comparable to venlafaxine ER. Larger sample sizes are required to confirm these results.

Discontinuation of hypnotics during cognitive behavioural therapy for insomnia

BackgroundIn practical sleep medicine, therapists face the question of whether or not to discontinue the ongoing use of hypnotics in patients, as well as the possible effects of discontinuation. The aim of this study was to evaluate the effects of discontinuing third-generation hypnotics on the results of cognitive-behavioural therapy (CBT) for primary insomnia in patients after long-term abuse.MethodsTwenty-eight outpatients were treated by CBT for 8 weeks. The treatment outcome was estimated by means of differences among subjective clinical scales and polysomnography variables assessed before and after the treatment period. The therapeutic effect in a subgroup of 15 patients who had previously received hypnotics and were successively withdrawn during weeks 2–6 was compared to the effect achieved in patients who had not used hypnotics before CBT.ResultsThere were no significant differences in baseline subjective and objective sleep characteristics between the hypnotic abusers and non-abusers. According to clinical scales and most polysomnographic measures, CBT was highly effective in both groups of subjects; it produced the greatest changes in total sleep time, REM sleep and sleep efficiency. Unexpectedly, discontinuation of hypnotics, as a factor in the analysis, was followed by an additional improvement of sleep efficiency and wake after sleep onset parameters.ConclusionOur study confirmed the efficacy of CBT in both hypnotic-abusing and non-abusing patients with chronic insomnia. The results of this study suggest that tapered withdrawal of third-generation hypnotics during CBT therapy for chronic insomnia could be associated with improvement rather than worsening of sleep continuity.

QEEG Theta Cordance in the Prediction of Treatment Outcome to Prefrontal Repetitive Transcranial Magnetic Stimulation or Venlafaxine ER in Patients With Major Depressive Disorder

The aims of this double-blind study were to assess and compare the efficacy of quantitative electroencephalographic (QEEG) prefrontal theta band cordance in the prediction of response to 4-week, right, prefrontal, 1-Hz repetitive transcranial magnetic stimulation (rTMS) or venlafaxine ER in patients with major depressive disorder (MDD). Prefrontal QEEG cordance values of 50 inpatients (25 subjects in each group) completing 4 weeks of the study were obtained at baseline and after 1 week of treatment. Depressive symptoms were assessed using Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and at week 1 and 4. Treatment response was defined as a ≥50% reduction in baseline MADRS total score. All responders (n = 9) and 6 of 16 nonresponders in the rTMS group had reduced cordance at week 1 (P < .01). Reduction of theta cordance value at week 1 was detected in all responders (n = 10) to venlafaxine ER, but only in 4 of 15 nonresponders (P = .005). The comparison of the areas under the curve of cordance change for prediction of response between rTMS (0.75) and venlafaxine ER (0.89) treated groups yielded no significant difference (P = .27). Our study indicates that prefrontal QEEG cordance is a promising tool not only for predicting the response to certain antidepressants but also to rTMS treatment, with comparable predictive efficacy for both therapeutic interventions.

Sleep spindles detection using Empirical Mode Decomposition

Sleep spindles are very important EEG patterns in modern neuroscience. There were developed many spindle detection algorithms, but not all of them are suitable for patients with insomnia because of artifacts, movements and complicated spindle producing. The paper presents a spindle detection method based on proper preprocessing and classification of stationary segments using Naive Bayes classifier. Preprocessing was performed using Empirical Mode Decomposition, which decomposes the signal into trends. Trends rejecting from the signal gives filtered signal for feature processing. To evaluate the quality of proposed approach, F-measure, positive predicative value and true positive rating were calculated. The method shows good results on dataset of 11 insomniac patient: F-measure by sample was 40.72% and F-measure by events was 48.59%. The results were also compared with Martin, Molle, Wendt and Ferallelli methods.

Is there a future for other glutamate receptor modulators in the pharmacotherapy of mood disorders

There is increasing evidence that some glutamatergic drugs could have antidepressant effects. Ketamine as a promising prototype for novel glutamatergic antidepressants has a much faster onset of action and is possibly more efficacious than standard antidepressants.1 Two recent systematic reviews and meta-analyses assessed the antidepressant efficacy (including modes of administration, duration of effect and adverse effects) of ketamine and other glutamate receptor modulators in the treatment of unipolar depression (Caddy et al ,2 in the Cochrane Database of Systematic Reviews), and, more generally, in mood disorders (Newport et al ,3 in the American Journal of Psychiatry). In their review, Caddy et al conducted searches of the Cochrane Depression, Anxiety and Neurosis Review Groups Specialised Register , which includes relevant randomised controlled trials (RCTs) mainly from the Cochrane Library, MEDLINE, EMBASE and PsycINFO. Additionally, they searched the WHOs trials portal (ICTRP) and ClinicalTrials.gov to identify unpublished or ongoing studies up to January 2015, and contacted authors to request additional trial data. The primary outcomes for this study were response rate and adverse events. Secondary outcomes included remission rate, mean end point scores or mean change scores, suicidality and drop-out rates. They included trials recruiting participants with treatment-resistant unipolar depression (except for one in the trial of Berman et al ) with all interventions as either monotherapy or combined with other treatments. Of note, the review of Caddy et al belongs to one of a pair of Cochrane reviews, which focuses on glutamate receptor modulators in bipolar disorder (BD).3 The authors rigorously assessed each trial for all potential sources of bias, namely, selection bias, performance bias, detection bias, attribution bias, reporting bias and other bias. They considered only data from the first phase of cross-over trials, calculated response rates out of the total number of randomised participants and applied …

Modafinil and Armodafinil

Wakefulness of adequately long duration and quality is in every respect essential for good quality of life. Inadequately low wakefulness named excessive daytime sleepiness (EDS) is defined as a reduced ability to maintain continuous wakefulness during the day. EDS may take the form of lapses into sleep or as periods of somnolence leading to sleep onset in favorable circumstances and longer total duration of sleep within 24 h. EDS lowers the quality of life and complicates or disallows many regular activities.

P.2.f.026 Clinical and neurophysiological biomarkers of ketamine's antidepressant effect in major depressive disorder patients

Results: HAM-D21 score decreased from the mean of 32.8±5.54 at baseline to 26.63±5.15 after 3 weeks, and 19.57±3.53 at 6 weeks with the final mean o 11.40±6.18 after 12 weeks. All the above changes were statistically significant (p 0.01). Equally significant reduction was found in the mean MADRS score; from 34.57±6.71 at baseline to 29.70±6.11 in 3 weeks, 20.13±5.03 in 6 weeks and 10.00±7.31 after 12 weeks of treatment. Further on, the mean HAM-A score was significantly reduced from the baseline mean of 36.20±4.15 to 30.27±4.05 in 3 weeks, 22.17±6.11 in 6 weeks and 12.23±8.41 in 12 weeks follow up. Significant decrease in severity of illness score was recorded with CGI, as well as significant global improvement of the subjects 7 (23.3%) of the subjects recovered, and 17 (56.7%) had a clinical response while 6 (20%) had improvement of symptoms. Deterioration of symptoms or severity of illness was not recorded. Tolerability of venlafaxine was excellent in 80% of the subjects and very good in the remaining 20%. Al of the subjects completed the 12 week course of treatment with venlafaxine. Conclusions: Venlafaxine proved to be an efficacious, safe and well tolerated agent for the treatment of Depressive disorder comorbid with Generalized anxiety disorder for the subjects in this study. Venlafaxine demonstrated fast clinical response in the majority of subjects. The results of this study provide further evidence about venlafaxine safety and tolerability [1−3]. This, together with the observation that the reduction of scores on HAM-D, HAM-A and MADRS were greater and faster in subjects with higher initial scores could lead us to the conclusion about the place of venlafaxine in the treatment of depression comorbid with anxiety. (Perhaps even in other psychiatric disorders whose hallmark can also be defined by depression and anxiety symptoms, such as chronic PTSD for example.) The limitation of this study is in a small number of subjects and the absence of a control group.

Contents Vol. 63, 2011

A. Drago, Naples G. Erdmann, Berlin A. Fischer, Göttingen J.M. Ford, San Francisco, Calif. S. Galderisi, Naples M. Hatzinger, Solothurn U. Hegerl, Leipzig K. Hirata, Mibu M. Kato, Osaka J. Kornhuber, Erlangen D. Lehmann, Zürich P. Monteleone, Naples G. Okugawa, Osaka G.N. Papadimitriou, Athens M. Popoli, Milano M. Reuter, Bonn F. Rösler, Marburg G. Ruigt, Oss J.K. Rybakowski, Poznan F. Schneider, Aachen R. Schwarting, Marburg M. Shigeta, Tokyo D. Souery, Brussels A. Steiger, Munich P. Willner, Swansea Associate Editors