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.     

Brain functional changes (QEEG cordance) and worsening suicidal ideation and mood symptoms during antidepressant treatment

Hunter AM, Leuchter AF, Cook IA, Abrams M. Brain functional changes (QEEG cordance) and worsening suicidal ideation and mood symptoms during antidepressant treatment. Objective: Antidepressant medications are efficacious overall; however, some individuals experience worsening mood symptoms and increased suicidal ideation (SI) during treatment. We examined the quantitative electroencephalographic (QEEG) cordance biomarker of brain function biomarker in relation to treatment‐emergent symptom worsening. Method: Seventy‐two major depressive disorder (MDD) subjects were treated with fluoxetine 20 mg (n = 13), venlafaxine 150 mg (n = 24), or placebo (n = 35) under double‐blind conditions. Behavioral ratings determined whether each subject demonstrated worsening of depressed mood, anxiety, or SI during treatment. QEEG cordance data were analyzed to determine whether symptom worsening was associated with neurophysiological changes. Results: Antidepressant treatment‐emergent SI (13.5%) was associated with a large transient decrease in midline‐and‐right‐frontal (MRF) cordance 48 h after start of medication. Conclusion: Hypothesis‐generating results suggest a pattern of functional changes in midline and right frontal brain regions associated with antidepressant treatment‐emergent SI in MDD.     

Prefrontal changes and treatment response prediction in depression

A continuing challenge in the treatment of depression is how to determine whether an effective drug has been selected for a particular patient, given that individuals will respond to some antidepressants but not others. The factors that contribute to response for each person have been examined from a variety of perspectives, both psychological and physiological. Advances in neuroimaging and in quantitative electroencephalography (QEEG) have made it possible to examine features of brain activity that are associated with response. A new QEEG measure, cordance, is correlated with regional cortical perfusion, and has been used with retrospective and prospective studies to evaluate specific findings that are predictive of clinical response in major depression. We present here a series of depressed subjects treated with antidepressants of different classes; decreases in prefrontal activity were seen as early as 48 hours into treatment in responders and were absent in nonresponders. These findings suggest a role for the prefrontal region in mediating response to medications with different mechanisms of action and raise the possibility of using new QEEG measures to identify changes in brain activity that are predictive of clinical outcome from antidepressant treatment.     

A pilot sequential study of cognitive therapy and pharmacotherapy of atypical depression.

BACKGROUND: Parallel comparison studies of cognitive therapy and antidepressant medication have suggested that both treatments are effective. However, we cannot determine from these studies whether cognitive therapy and antidepressant medication are effective for the same populations of depressives. A sequential study in which nonresponders to the first treatment are then treated with the second can address this issue. METHOD: Twenty-seven patients meeting DSM-III criteria for major depression or dysthymic disorder and Columbia criteria for atypical depression received cognitive therapy followed by antidepressant medication for cognitive therapy nonresponders. A response rate with the second treatment equal to that expected with placebo would suggest both treatments target the same depressive population. RESULTS: Of the 25 completers of the study, 14 (56%) were judged responders to cognitive therapy alone. Sixty-nine percent (9/13) of the responders maintained their benefits for 6 months or more. Seven of the 11 cognitive therapy nonresponders (63%) responded to antidepressant medication. These results were compared with those of a concurrent double-blind medication study; both its sample and ours were drawn from the same population at the same time: cognitive therapy and antidepressant medication response rates were higher than expected with placebo (28%). CONCLUSION: The results suggest that (1) cognitive therapy and antidepressant medication are effective treatments for differing populations of depressed patients, as the antidepressant medication response of cognitive therapy nonresponders was greater than expected with placebo, and (2) cognitive therapy has a lasting effect.     

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.     

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.     

Antidepressant response trajectories and quantitative electroencephalography (QEEG) biomarkers in major depressive disorder

Individuals with Major Depressive Disorder (MDD) vary regarding the rate, magnitude and stability of symptom changes during antidepressant treatment. Growth mixture modeling (GMM) can be used to identify patterns of change in symptom severity over time. Quantitative electroencephalographic (QEEG) cordance within the first week of treatment has been associated with endpoint clinical outcomes but has not been examined in relation to patterns of symptom change. Ninety-four adults with MDD were randomized to eight weeks of double-blinded treatment with fluoxetine 20 mg or venlafaxine 150 mg (n = 49) or placebo (n = 45). An exploratory random effect GMM was applied to Hamilton Depression Rating Scale (Ham-D₁₇) scores over 11 timepoints. Linear mixed models examined 48-h, and 1-week changes in QEEG midline-and-right-frontal (MRF) cordance for subjects in the GMM trajectory classes. Among medication subjects an estimated 62% of subjects were classified as responders, 21% as non-responders, and 17% as symptomatically volatile—i.e., showing a course of alternating improvement and worsening. MRF cordance showed a significant class-by-time interaction (F_(2,41) = 6.82, p = .003); as hypothesized, the responders showed a significantly greater 1-week decrease in cordance as compared to non-responders (mean difference = −.76, Std. Error = .34, df = 73, p = .03) but not volatile subjects. Subjects with a volatile course of symptom change may merit special clinical consideration and, from a research perspective, may confound the interpretation of typical binary endpoint outcomes. Statistical methods such as GMM are needed to identify clinically relevant symptom response trajectories.     

Rostral anterior cingulate cortex theta current density and response to antidepressants and placebo in major depression

ObjectiveTo assess whether pretreatment theta current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC) differentiates responders from non-responders to antidepressant medication or placebo in a double-blinded study.MethodsPretreatment EEGs were collected from 72 subjects with Major Depressive Disorder (MDD) who participated in one of three placebo-controlled trials. Subjects were randomized to receive treatment with fluoxetine, venlafaxine, or placebo. Low-resolution brain electromagnetic tomography (LORETA) was used to assess theta current density in the rACC and mOFC.ResultsMedication responders showed elevated rACC and mOFC theta current density compared to medication non-responders (rACC: p = 0.042; mOFC: p = 0.039). There was no significant difference in either brain region between placebo responders and placebo non-responders.ConclusionsTheta current density in the rACC and mOFC may be useful as a biomarker for prediction of response to antidepressant medication.SignificanceThis is the first double-blinded treatment study to examine pretreatment rACC and mOFC theta current density in relation to antidepressant response and placebo response. Results support the potential clinical utility of this approach for predicting clinical outcome to antidepressant treatments in MDD.     

Pretreatment neurophysiologic function and ECT response in depression

OBJECTIVES: Recent brain imaging studies have provided evidence that brain function assessed prior to treatment of depression may be associated with eventual treatment response. The present study tested the hypothesis that brain activity in midline apical quantitative EEG (QEEG) electrodes would be associated with therapeutic response to electroconvulsive therapy (ECT). METHODS: Ten treatment-refractory patients with unipolar or bipolar depression received a Hamilton Rating Scale for Depression (Ham-D) at baseline, during, and following ECT treatment. Resting, eyes-closed, 35-lead QEEG recordings were done 1 day before the initial ECT treatment. Data were analyzed using QEEG power and cordance. RESULTS: The mean of the theta-band pretreatment cordance from the central brain region was strongly associated with percentage decrease in Ham-D score over the course of treatment (r = 0.80, P = 0.005). QEEG cordance from other brain regions and power from all brain regions did not show an association with clinical improvement. CONCLUSIONS: Depressed subjects with higher pretreatment central cordance appear to be more likely to experience therapeutic benefits of ECT. The location of central electrodes over the cingulate cortex may indicate that pretreatment cingulate activity is associated with response to ECT.     

Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression.

BACKGROUND: Pretreatment functional brain imaging was examined for never-hospitalized outpatients with unipolar depression compared with control subjects in a crossover treatment trial involving bupropion or venlafaxine monotherapy. METHODS: Patients (n = 20) with unipolar depression received baseline (medication-free) fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) scan and then at least 6 weeks of bupropion or venlafaxine monotherapy in a single-blind crossover trial. Age-matched healthy control subjects (n = 20) also received baseline FDG PET scans. For each medication PET data from patients compared with control subjects was analyzed as a function of treatment response (defined as moderate to marked improvement on the Clinical Global Impression Scale). RESULTS: Treatment response rates were similar for buproprion (32%) and venlafaxine (33%). Compared with control subjects, responders but not nonresponders, to both drugs demonstrated frontal and left temporal hypometabolism. Selectively, compared with control subjects bupropion responders (n = 6) also had cerebellar hypermetabolism, whereas venlafaxine responders (n = 7) showed bilateral temporal and basal ganglia hypometabolism. CONCLUSIONS: These data suggest that pretreatment frontal and left temporal hypometabolism in never-hospitalized depressed outpatients compared with control subjects is linked to positive antidepressant response and that additional alterations in regional metabolism may be linked to differential responsivity to bupropion and venlafaxine monotherapy.     

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.     

The change of QEEG prefrontal cordance as a response predictor to antidepressive intervention in bipolar depression. A pilot study

ObjectivesThe aim of the study was to examine whether the change of quantitative EEG (QEEG) theta prefrontal cordance after one week of various antidepressive interventions predicts response to a 4-week treatment in patients with bipolar depression.MethodsWe investigated 20 inpatients who completed a 4-week treatment. EEG data were monitored at baseline and after 1 week of treatment. QEEG cordance was computed at 3 frontal electrodes (Fp1, Fp2, Fz) in theta frequency band. Depressive symptoms and clinical status were assessed using Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression (CGI) and Young Mania Rating Scale (YMRS).ResultsSeven of 8 responders (reduction of MADRS ≥50%) and only 2 of 12 non-responders had decreased prefrontal theta cordance value after the first week of treatment (p = 0.02). The positive and negative predictive values of cordance reduction for response were 0.78 and 0.91, respectively. We also found significant differences in cordance value reductions between responders and non-responders after week 1 and higher baseline cordance in responders. Conclusion: The change in prefrontal theta cordance was associated with subsequent change in depressive symptoms and potentially might be a useful tool in the early detection of acute response to antidepressive interventions in bipolar depressed patients.     

A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly

Rapid transcranial magnetic stimulation (rTMS) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects. Older depressed patients, however, in one study showed a lower response rate than younger patients. The current study examined treatment response in 20 depressed, treatment-refractory patients (mean age 60.7 +/- 9.8 years) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80% of motor threshold or identical placebo stimulation, after patients had been withdrawn from their antidepressants. There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days' follow-up. There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders (p = .03). These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS.     

Influence of age, gender, health status, and depression on quantitative EEG

Quantitative electroencephalography (QEEG) has shown increasing utility in assessing brain function in clinical research studies of depression. QEEG findings may be influenced by a variety of factors other than the presence of depression, including age, gender, depression severity, and physical health status. Many of these factors have not been systematically evaluated. We therefore examined QEEG measures in 104 subjects with depression and normal controls to determine the influence of these factors. We examined QEEG power as well as cordance, a QEEG measure that has a stronger association with cerebral perfusion than conventional QEEG measures. Prefrontal cordance in the theta band has been associated with the pathophysiology of depression and response to treatment. We found that prefrontal cordance and relative power in the theta band were unaffected by age, gender, severity of depression, and health status, while prefrontal absolute power was higher in women than men. All of these measures were different from global measures of absolute and relative power, which were influenced by age, gender, and health status. These findings suggest that prefrontal cordance in depressed patients is not significantly affected by factors of age, gender, severity of depression, or physical illness. Global measures of power, and to a lesser extent prefrontal absolute power, must be interpreted with regard to confounding factors of age, gender, physical illness, and severity of depression.     

Baseline characteristics of 10-day placebo washout responders in antidepressant trials

In antidepressant drug trials, the randomized treatment phase is usually preceded by a single-blind placebo period or "washout." Ninety-four depressed patients who improved during this 10-day placebo period constitute our study focus. Analysis of baseline and postplacebo measures showed that the 10-day placebo responders in our sample were convincingly depressed at baseline and improved significantly after placebo washout. This group of patients differed from 6-week placebo responders in our randomized trials in being more mildly ill, being more chronic, containing fewer cases of primary depression, and having fewer illness precipitants. They differed from placebo nonresponders largely in manifesting milder illness symptoms across the range of psychopathology. The proportion of placebo washout responders declined in the winter months.     

Enhanced signal transduction by adenylate cyclase in platelet membranes of patients showing antidepressant responses to alprazolam: preliminary data

The triazolobenzodiazepine, alprazolam, was administered to 11 depressed patients over a period of six weeks, and six patients showed a favorable antidepressant response. There were no significant differences between responders and nonresponders in age, pretreatment Hamilton Depression Rating Scores, 4 p.m. postdexamethasone plasma cortisol levels, or platelet monoamine oxidase activities. Blood levels of alprazolam were not meaningfully different in responders and nonresponders when measured on treatment day 8. However, on treatment day 8, significantly enhanced prostaglandin D2-stimulated platelet adenylate cyclase activity, greater suppression of prostaglandin D2-stimulated platelet adenylate cyclase activity by epinephrine, and enhanced sodium fluoride-stimulated platelet adenylate cyclase activity were seen in the six patients who went on to respond to alprazolam, but not in the five nonresponders. In contrast, there were no significant changes in prostaglandin D2, (-)-isoproterenol, or fluoride ion-stimulated leukocyte adenylate cyclase activity in responders or nonresponders. No meaningful changes were observed in the mean densities of either the high-affinity platelet alpha 2-adrenergic receptor (for 3H-p-aminoclonidine) or the leukocyte beta-adrenergic receptor (for 3H-dihydroalprenolol) in responders or nonresponders. The present findings, taken in conjunction with findings from other recent studies, suggest that enhanced coupling between certain neurotransmitter or hormone receptors and adenylate cyclase through the guanine nucleotide regulatory proteins may help explain the antidepressant effects of alprazolam and possibly other forms of antidepressant treatment.     

Effect of sleep deprivation on brain metabolism of depressed patients.

OBJECTIVE: Sleep deprivation is a rapid, nonpharmacologic antidepressant intervention that is effective for a subset of depressed patients. The objective of this study was to identify which brain structures' activity differentiates responders from nonresponders and to study how metabolism in these brain regions changes with mood. METHOD: Regional cerebral glucose metabolism was assessed by positron emission tomography (PET) with [18F]deoxyglucose (FDG) before and after total sleep deprivation in 15 unmedicated awake patients with unipolar major depression and 15 normal control subjects, who did the continuous performance test during FDG uptake. RESULTS: After sleep deprivation, four patients showed a 40% or more improvement on the Hamilton Rating Scale for Depression. Before sleep deprivation the depressed responders had a significantly higher cingulate cortex metabolic rate than the depressed nonresponders, and this normalized after sleep deprivation. The normal control subjects and nonresponding depressed patients showed no change in cingulate metabolic rate after sleep deprivation. CONCLUSIONS: Overactivation of the limbic system as assessed by PET scans may characterize a subset of depressed patients. Normalization of activity with sleep deprivation is associated with a decrease in depression.     

Changes in brain function (quantitative EEG cordance) during placebo lead-in and treatment outcomes in clinical trials for major depression

OBJECTIVE: Decreases in prefrontal electroencephalogram (EEG) cordance that are detectable as early as 48 hours after the start of medication have been related to clinical outcome in treatment trials for major depressive disorder. The relationship between brain changes during the placebo lead-in phase and medication treatment outcome is unknown. The authors hypothesized that decreases in prefrontal cordance during the placebo lead-in phase would be associated with better clinical outcome in subjects treated with antidepressants. METHOD: Data were pooled examining 51 adults with major depressive disorder from two independent double-blind placebo-controlled trials. A 1-week single-blind placebo lead-in phase preceded 8 weeks of randomized treatment with medication (fluoxetine 20 mg or venlafaxine 150 mg) or placebo. The authors obtained quantitative EEG cordance measures at baseline and at the end of the placebo lead-in period. Relationships between regional cordance changes at the end of the placebo lead-in period and clinical outcome (the final 17-item Hamilton Rating Scale for Depression scores) were examined using multiple linear regression analysis. RESULTS: As hypothesized, decreases in prefrontal cordance during the placebo lead-in period were associated with lower final Hamilton depression scale scores in subjects randomly assigned to medication. Prefrontal changes explained 19% of the variance in final Hamilton depression scale scores. CONCLUSIONS: Neurophysiological changes during a placebo lead-in period may serve as nonpharmacodynamic biomarkers of eventual treatment outcomes in clinical trials for major depressive disorder.     

The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication

BACKGROUND: A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo. METHOD: Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John's wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John's wort or placebo were treated with an antidepressant for 24 weeks. RESULTS: During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John's wort extract, 5 (29.4%) relapsed. CONCLUSIONS: The subjects who did not respond to St. John's wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.     

Neurophysiologic predictors of treatment response to fluoxetine in major depression.

Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0+/-7.5 vs. 19.6+/-4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0+/-9.4 vs. 27.8+/-3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0+/-5.0 vs. 23.8+/-4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants.