Changes in QEEG prefrontal cordance as a predictor of response to antidepressants in patients with treatment resistant depressive disorder: a pilot study

INTRODUCTION: Previous studies of patients with unipolar depression have shown that early decreases of EEG cordance (a new quantitative EEG method) can predict clinical response. We examined whether early QEEG decrease represents a phenomenon associated with response to treatment with different antidepressants in patients with treatment resistant depression. METHOD: The subjects were 17 inpatients with treatment resistant depression. EEG data and response to treatment were monitored at baseline and after 1 and 4 weeks on an antidepressant treatment. QEEG cordance was computed at three frontal electrodes in theta frequency band. The prefrontal cordance combines complementary information from absolute and relative power of EEG spectra. Recent studies have shown that cordance correlates with cortical perfusion. Depressive symptoms were assessed using Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: All 17 patients completed the 4-week study. All five responders showed decreases in prefrontal cordance after the first week of treatment. Only 2 of the 12 nonresponders showed early prefrontal cordance decrease. The decrease of prefrontal QEEG cordance after week 1 in responders as well as the increase in nonresponders were both statistically significant (p-value 0.03 and 0.01, respectively) and the changes of prefrontal cordance values were different between both groups (p-value 0.001). CONCLUSION: Our results suggest that decrease in prefrontal cordance may indicate early changes of prefrontal activity in responders to antidepressants. QEEG cordance may become a useful tool in the prediction of response to antidepressants.     

Early reduction in prefrontal theta QEEG cordance value predicts response to venlafaxine treatment in patients with resistant depressive disorder

INTRODUCTION: Previous studies of patients with unipolar depression have shown that early decrease of prefrontal EEG cordance in theta band can predict clinical response to various antidepressants. We have now examined whether decrease of prefrontal quantitative EEG (QEEG) cordance value after 1 week of venlafaxine treatment predicts clinical response to venlafaxine in resistant patients. METHOD: We analyzed 25 inpatients who finished 4-week venlafaxine treatment. EEG data were monitored at baseline and after 1 week of treatment. QEEG cordance was computed at three frontal electrodes in theta frequency band. Depressive symptoms and clinical status were assessed using Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory-Short Form (BDI-S) and Clinical Global Impression (CGI). RESULTS: Eleven of 12 responders (reduction of MADRS >or=50%) and only 5 of 13 non-responders had decreased prefrontal QEEG cordance value after the first week of treatment (p=0.01). The decrease of prefrontal cordance after week 1 in responders was significant (p=0.03) and there was no significant change in non-responders. Positive and negative predictive values of cordance reduction for response were 0.7 and 0.9, respectively. CONCLUSION: The reduction of prefrontal theta QEEG cordance value after first week of treatment might be helpful in the prediction of response to venlafaxine.     

Cognitive therapy for bipolar depression: a pilot study.

OBJECTIVE: While the efficacy of cognitive-behaviour therapy (CBT) for the treatment of acute unipolar major depression is well-documented, there is almost no data evaluating its utility in the treatment of bipolar depression. This pilot study compares the efficacy of CBT combined with mood-stabilizer pharmacotherapy for bipolar depression and CBT alone for unipolar depression. METHOD: A matched-case control design was used to evaluate outcomes following 20 sessions of CBT in 11 depressed bipolar patients and 11 matched recurrent unipolar depressed control subjects. RESULTS: Bipolar depressed patients achieved similar levels of reduction in depressive symptoms following CBT, as did the unipolar depressed group. However, on measures of more pervasive dysfunctional attitudes, bipolar patients did not improve to the same degree. CONCLUSIONS: Preliminary findings suggest that CBT warrants further investigation as an effective psychosocial intervention for depression in bipolar patients already receiving ongoing mood-stabilizing pharmacotherapy.     

The cortisol awakening response in bipolar illness: a pilot study.

OBJECTIVE: A growing body of data suggests that a significantly enhanced salivary cortisol response to waking may indicate an enduring tendency to abnormal cortisol regulation. Our objective was to apply the response test to a population already known to have long-term hypothalamo-pituitary-adrenocortical (HPA) axis dysregulation. We hypothesized that the free cortisol response to waking, believed to be genetically influenced, would be elevated in a significant percentage of cases, regardless of the afternoon Dexamethasone Suppression Test (DST) value. METHOD: Using the free cortisol response to waking and the short daytime profile, we tested 18 clinically stable, lithium-responsive subjects from our long-term naturalistic follow-up of monthly DSTs. These tests include salivary testing every 15 minutes during the first hour of waking, followed by samples taken at 3:00 PM and 8:00 PM. RESULTS: While clinically stable on lithium prophylaxis, patients with bipolar disorder (BD) showed a significantly enhanced salivary cortisol response to waking, compared with control subjects (P < 0.03). Cortisol levels 30 minutes after waking significantly exceeded those in the large normative data provided in the literature (P < 0.001). CONCLUSIONS: Our observations support the hypothesis that the free cortisol response to waking can reflect relatively enduring HPA dysregulation, even when lithium-responsive BD patients are clinically well and their DSTs are normal. Because the test is easy to administer, the free cortisol response to waking may hold promise as a marker in studies of high-risk families predisposed to, or at risk for, mood disorders.     

Frontal theta cordance predicts 6-month antidepressant response to subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study

Deep brain stimulation (DBS) of subcallosal cingulate white matter (SCC) may be an effective approach for treatment-resistant depression (TRD) that otherwise fails to respond to more conventional therapies, but DBS is invasive, costly, and has potential for adverse effects. Therefore, it is important to identify potential biomarkers for predicting antidepressant response before intervention. Resting-state EEG was recorded from 12 TRD patients at pre-treatment baseline, after 4 weeks SCC DBS, and after 24 weeks SCC DBS. Lower frontal theta cordance (FTC) at baseline (and higher FTC after 4 weeks) predicted lower depression severity scores after 24 weeks. Greater FTC increases (baseline-4 weeks) predicted greater decreases in depression severity scores subsequently (4-24 weeks) and over the course of the study (baseline-24 weeks). Predictive relationships were topographically specific to theta cordance for frontal electrodes. Thus, results from this pilot study suggest that baseline FTC and changes early in treatment each have utility as biomarkers for predicting 6-month clinical response to SCC DBS for TRD.     

Partial response as a predictor of outcome in geriatric depression.

OBJECTIVE: Although geriatric depression generally responds to treatment, patients are often left with residual symptoms after acute treatment. Data are lacking on the eventual outcomes of individuals who are partial responders or poor responders to initial treatment. METHODS: The authors examined 200 patients initially treated with a treatment-based guideline approach that allowed for physician choice. RESULTS: After 3 months, 34.0% of patients were remitted, 37.5% had achieved a partial response, and 28.5% were still highly symptomatic. After 6 months of treatment, 51.1% of patients were remitted, 36.5% were partial responders, and 12.5% were still experiencing significant depressive symptoms. Cumulative remission rates over 18 months of treatment were significantly higher among partial responders than among highly symptomatic patients at 6 months, but not at 3 months. In terms of relapse, defined as a Montgomery-Asberg Depression Rating Scale score greater than 15, 42.0% of the remitted and partial-responder groups had relapsed by 18 months. When compared with remitted patients, partial responders at 6 months were more likely to experience a relapse. There were no differences in relapse rate between the two groups at 3 months. CONCLUSION: These results suggest that during ongoing active treatment of geriatric depression, the level of improvement at 6 months, but not 3 months, is predictive of subsequent course.     

Motivation to change as a predictor of treatment response in obsessive compulsive disorder.

BACKGROUND: Motivation to change has been shown to predict treatment outcome in various areas of mental health but has never been examined in obsessive compulsive disorder (OCD). The purpose of this report is to present the first use of the University of Rhode Island Change Assessment (URICA) in an OCD pharmacotherapy sample and to determine whether motivation to change predicts degree of treatment response in this group. METHODS: The sample consisted of 32 outpatients diagnosed with OCD who completed an open-label 10-week trial of fluvoxamine. Participants completed the URICA at baseline. OCD symptom severity was rated at baseline and end of treatment. RESULTS: While overall readiness was not related to change in severity, high scores on the Precontemplation subscale (indicating greater resistance to changing OC behaviors) were associated with less change pre- to post-treatment. CONCLUSIONS: Preliminary findings indicate that greater resistance to change is associated with less improvement in OCD symptom severity following pharmacotherapy. As this is the first use of the URICA as a predictor of OCD response, future research should further examine the role of motivation to change in treatment outcome in a larger OCD sample.     

Sleep deprivation as a predictor of response to light therapy in major depression

Light therapy (LT) is regarded as the treatment of choice for seasonal affective disorder (SAD). In nonseasonal depression the results of light therapy are nonconclusive. Sleep deprivation (SD), however, is effective in 50-60% of the patients with major depression. The predictive value of Total Sleep Deprivation (TSD) for the treatment outcome of antidepressiva has been already examined. Purpose of the present study was to test whether light therapy is more beneficial in TSD responders than in TSD nonresponders. 40 inpatients with major depressive disorder completed one night of TSD. Twenty TSD responders and 20 TSD nonresponders were randomly assigned to 14 days of bright light therapy (2500 lux, 7-9 a.m.) or 14 days of dim light therapy (red light 50 lux, 7-9 a.m.). Manova with repeated measurements revealed a significant difference in the course of depression over the time between TSD responders and nonresponders, but no significant difference between bright and dim light. Questions of placebo effect, of SAD and of personality variables as predictors of response to SD and LT are being discussed.     

Delta sleep ratio as a predictor of sleep deprivation response in major depression.

The fast but short-lasting improvement of depressive symptoms by sleep deprivation (SD) in about 60% of patients with a major depressive disorder is well established, but the mechanisms of action are still not clear. Recent studies suggest that changes in non rapid eye movement (NREM) sleep, especially in slow wave activity (SWA), could be associated with the therapeutic outcome of SD. In the current study, spectral analysis of NREM sleep EEG directly prior to SD was performed to determine if automatically derived sleep parameters predict SD response. Sixteen pair matched and drug free patients with a major depressive disorder, 8 SD responders and 8 non-responders (response criterion: 50% reduction on the 6-item HAMD score), were included. Average EEG spectral power was calculated for the whole night before SD and for single NREM episodes. While whole-night averages of spectral power did not differ significantly between subgroups, SD responders showed a steady decrease of SWA across successive NREM episodes, whereas in non-responders an increase from the first to the second episode was observed. The different distribution of SWA was significantly expressed in the delta sleep ratio (quotient of SWA in the first to the second NREM episode). In conclusion, a high delta sleep ratio is a positive predictor for SD response. Referred to psycho- and pharmacotherapeutic results it is hypothesized that low and high values of the delta sleep ratio characterize subgroups of depressed patients with different neurobiological alterations, which could be relevant for further scientific and therapeutic approaches.     

Crisis intervention response and long-term outcome: a pilot study.

We investigated whether process variables (therapeutic alliance and insight) measured at the termination of crisis intervention predict long-term treatment compliance and 2-year outcome. Thirty-seven consecutive depressed psychiatric patients assigned to outpatient crisis intervention (CCI) were assessed with both questionnaires and standardized instruments at intake, 1 week, and CCI termination (mean, 6 weeks). Thirty-one subjects (84%) were also evaluated at 1-year and 2-year follow-up. We found that working alliance and development of insight predicted positive global change and symptom improvement at 1 and 2 years' follow-up. Furthermore, the observed correlation between process measures and 2-year outcome was found to be independent of age, sex, symptoms severity at intake, improvement of symptoms at CCI termination, premorbid adjustment, DSM-III-R axis I/axis II diagnosis, and therapeutic alliance at intake.     

The thyrotropin response to thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients.

We evaluated the predictive value of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in 32 depressed outpatients completing a double-blind placebo-controlled trial of s-adenosyl-l-methionine (SAMe), which failed to show any significant difference between SAMe and placebo. Treatment response was defined as the change in Hamilton Rating Scale for Depression (HRSD-24) score between baseline and the end of the six-week trial. Subjects with TSH response outside the normal range (7-25 uU/ml) had a significantly greater response than patients with a normal response. There was also a significant correlation between absolute deviations from the mean TSH response (16 uU/ml) and changes in HRSD-24 scores.     

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy

Objectives:  Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
Methods:  We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Results:  Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 – 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks ( t =−0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t =1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment ( t =1.11, p=0.28).
Conclusions:  Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.     

HPA axis activation in major depression and response to fluoxetine: a pilot study

Hypothalamic-pituitary-adrenal (HPA) axis activation is a frequently observed phenomenon in major depression. However, whether this activation has any implications for treatment is unknown. To address this question, we examined baseline response to metyrapone and 6-week response to fluoxetine. Premenopausal women (n = 20) who met criteria for major depression with no other confounding Axis I disorders, medications, or medical illnesses and were not taking hormonal contraceptives were evaluated with an evening metyrapone challenge before the onset of treatment. Twenty-one normal women were also studied with the evening metyrapone challenge. The depressed patients then entered an open label treatment with fluoxetine for 6 weeks. Subjects were classified as responders if they demonstrated a 50% or greater decrease in Hamilton Depression Rating Scale rating. As a group, the depressed women demonstrated significantly increased ACTH secretion compared to control women before the onset of treatment, during the metyrapone challenge. Before treatment, women who were non-responders to fluoxetine showed increased HPA axis activation compared to controls, while the fluoxetine responders did not differ significantly from normal subjects in their ACTH levels during metyrapone challenge. These results suggest that overactivity of the HPA axis may be one factor associated with slower response to fluoxetine. This may reflect the greater severity of subjects with HPA axis dysregulation or the need to normalize the HPA axis with medications for optimal response.     

Heart rate variability and cordance in rapid eye movement sleep as biomarkers of depression and treatment response

ObjectivesThe relevance of rapid eye movement (REM) sleep in affective disorders originates from its well-known abnormalities in depressed patients, who display disinhibition of REM sleep reflected by increased frequency of rapid eye movements (REM density). In this study we examined whether heart rate variability (HRV) and prefrontal theta cordance, both derived from REM sleep, could represent biomarkers of antidepressant treatment response.MethodsIn an open-label, case-control design, thirty-three in-patients (21 females) with a depressive episode were treated with various antidepressants for four weeks. Response to treatment was defined as a ≥50% reduction of HAM-D score at the end of the fourth week. Sleep EEG was recorded after the first and the fourth week of medication. HRV was derived from 3-min artifact-free electrocardiogram segments during REM sleep. Cordance was computed for prefrontal EEG channels in the theta frequency band during tonic REM sleep.ResultsHRV during REM sleep was decreased in depressed patients at week four as compared to controls (high effect size; Cohen's d > 1), and showed a negative correlation with REM density in both, healthy subjects and patients at week four. Further, the fourteen responders had significantly higher prefrontal theta cordance as compared to the nineteen non-responders after the first week of antidepressant medication; in contrast, HRV at week one did not discriminate between responders and non-responders.ConclusionsOur data suggest that HRV in REM sleep categorizes healthy subjects and depressed patients, whereas REM sleep-derived prefrontal cordance may predict the response to antidepressant treatment in depressed patients.     

Changes in prefrontal activity characterize clinical response in SSRI nonresponders: a pilot study

Previous studies in unipolar depression have shown that early decreases in prefrontal values of the QEEG cordance measure identified responders to pharmacotherapy. These studies have all examined individuals who were drug-free prior to the first physiologic assessment, yet in the clinical management of treatment resistant depression (TRD), many patients undergo changes in treatment without a drug-free interval between treatments. Here, we investigated whether cordance decreases were associated with response in Stage I TRD subjects without wash-out between treatment trials. Awake EEGs were recorded from 12 adults with unipolar depression. Subjects were receiving naturalistic treatment, had failed SSRI monotherapy, and were starting a new treatment prescribed by their treating psychiatrists. EEG data were recorded before starting the new treatment and after approximately 1 week. Six of the 12 subjects responded to treatment after 8--10 weeks. Five of the six responders showed an early cordance decreases, compared with two of the six nonresponders (accurate characterization in 75% of the cases). Consistent with previous treatment trials, decreases in prefrontal cordance differentiated responders from nonresponders in this setting as well. These findings suggest that cordance biomarkers may be a useful tool in effectiveness trials that parallel clinical practices in SSRI nonresponders, and may not require a wash-out period between treatments.     

Rapid response to the addition of lithium in iprindole-resistant unipolar depression: a pilot study

The authors administered lithium carbonate, 900 mg/day, in an open study to seven patients with a major unipolar depression refractory to 3-week treatment with iprindole, 90 mg/day, a tricyclic antidepressant devoid of any action on monoaminergic reuptake. All patients showed clinically significant improvement within 48 hours. Since iprindole induces in the animal a sensitization of forebrain neurons to serotonin (5-HT), as do other tricyclic antidepressants, and lithium enhances the activity of 5-HT neurons, the authors propose that an enhanced release of 5-HT on sensitized target neurons might underlie the rapid antidepressant effect in tricyclic-refractory depression when lithium is added to the treatment regimen.     

A pilot study of standardized treatment in geriatric bipolar disorder.

OBJECTIVE: The authors sought to determine the feasibility of treating elderly adults with bipolar disorder under standardized-treatment conditions. METHODS: Thirty-one patients age 60 and older with bipolar disorder were treated in standardized pathways. Mood state was checked at each study visit with the Hamilton Rating Scale for Depression-17 item (Ham-D-17) and the Young Mania Rating Scale (YMRS). RESULTS: Defining "well days" as both Ham-D and YMRS scores of 相似文献   

Neuroticism as a predictor of outcome in depression

Low levels of neuroticism have variably been associated with a better outcome of depressive disorders but the interpretation of this phenomenon is clouded by the knowledge that severity of depression may itself confound ratings of neuroticism. To clarify any relationship between neuroticism and outcome, the authors assessed the predictability of neuroticism (as assessed by questionnaire, psychiatrist rating, and subject self-report) in separate groups of psychiatric patients and symptomatic volunteers with nonmelancholic depression. Depressives' judgments of their own neuroticism correlated with neuroticism scores on the Eysenck Personality Inventory (EPI), but neither of these measures predicted improvement at 6 nor 20 weeks. Judgments of neuroticism made by psychiatrists, which did not correlate with EPI neuroticism scores, did predict improvement. The study suggests that differences in defining neuroticism contribute to its variable association with outcome and further suggests the relevance of clinically assessing neuroticism as a personality variable.