Gender and racial/ethnic differences in physiologic responses in the Stimulant Reduction Intervention using Dosed Exercise Study.

Exercise may be beneficial for individuals in substance use disorder (SUD) treatment given the higher rates of both medical and psychiatric comorbidity, namely mood and anxiety disorders, compared to the general population. Gender and/or racial/ethnic differences in health benefits and response to prescribed exercise have been reported and may have implications for designing exercise interventions in SUD programs. METHOD: Data are from the National Drug Abuse Treatment Clinical Trials Network (NIDA/CTN) Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial. Gender differences across racial/ethnic groups in physiological responses and stimulant withdrawal severity across time were analyzed using linear mixed effects models. RESULTS: Males completed significantly more exercise sessions than females and were more adherent to the prescribed exercise dose of 12 Kcal/Kg/Week. Controlling for age, race/ethnicity, treatment group and stimulant withdrawal severity, there was a significant gender by time interaction for body mass index (BMI) (p < 0.001), waist circumference (p < 0.001) and heart rate measured prior to exercise sessions (p < 0.01). For females, body mass index (BMI) and waist circumference increased over time while for males BMI and waist circumference stayed unchanged or slightly decreased with time. Heart rate over time significantly increased for females at a higher rate than in males. Stimulant withdrawal severity was similar in males and females at baseline but males exhibited a significant decrease over time while females did not. Although baseline differences were observed, there were no time by race/ethnicity differences in physiologic responses. DISCUSSION: Gender differences in response to exercise may have implications for developing gender specific exercise interventions in SUD programs.

Racial and ethnic differences in treatment outcomes among adults with stimulant use disorders after a dosed exercise intervention.

The current study examined differences in substance abuse treatment outcomes among racial and ethnic groups enrolled in the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial, a multisite randomized clinical trial implemented through the National Institute on Drug Abuse's (NIDA's) Clinical Trials Network (CTN). STRIDE aimed to test vigorous exercise as a novel approach to the treatment of stimulant abuse compared to a health education intervention. A hurdle model with a complier average causal effects (CACE) adjustment was used to provide an unbiased estimate of the exercise effect had all participants been adherent to exercise. Among 214 exercise-adherent participants, we found significantly lower probability of use for Blacks (z = -2.45, p = .014) and significantly lower number of days of use for Whites compared to Hispanics (z = -54.87, p = <.001) and for Whites compared to Blacks (z = -28.54, p = <.001), which suggests that vigorous, regular exercise might improve treatment outcomes given adequate levels of adherence.

IL-1ß and BDNF are associated with improvement in hypersomnia but not insomnia following exercise in major depressive disorder.

Given the role of sleep in the development and treatment of major depressive disorder (MDD), it is becoming increasingly clear that elucidation of the biological mechanisms underlying sleep disturbances in MDD is crucial to improve treatment outcomes. Sleep disturbances are varied and can present as insomnia and/or hypersomnia. Though research has examined the biological underpinnings of insomnia in MDD, little is known about the role of biomarkers in hypersomnia associated with MDD. This paper examines biomarkers associated with changes in hypersomnia and insomnia and as predictors of improvements in sleep quality following exercise augmentation in persons with MDD. Subjects with non-remitted MDD were randomized to augmentation with one of two doses of aerobic exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. The four sleep-related items on the clinician-rated Inventory of Depressive Symptomatology (sleep onset insomnia, mid-nocturnal insomnia, early morning insomnia and hypersomnia) assessed self-reported sleep quality. Inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-6) and brain-derived neurotrophic factor (BDNF) were assessed in blood samples collected before and following the 12-week intervention. Reduction in hypersomnia was correlated with reductions in BDNF (ρ = 0.26, P = 0.029) and IL-1ß (ρ = 0.37, P = 0.002). Changes in these biomarkers were not associated with changes in insomnia; however, lower baseline levels of IL-1ß were predictive of greater improvements in insomnia (F = 3.87, P = 0.050). In conclusion, improvement in hypersomnia is related to reductions in inflammatory markers and BDNF in persons with non-remitted MDD. Distinct biological mechanisms may explain reductions in insomnia.

A computational analysis of flanker interference in depression.

BACKGROUND: Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. METHOD: One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials). RESULTS: Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = -0.28, p = 0.007). CONCLUSIONS: Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.

A significant dose-dependent relationship between mercury exposure from dental amalgams and kidney integrity biomarkers: a further assessment of the Casa Pia children's dental amalgam trial.

Dental amalgams are a commonly used dental restorative material. Amalgams are about 50% mercury (Hg), and Hg is known to significantly accumulate in the kidney. It was hypothesized that because Hg accumulates in the proximal tubules (PTs), glutathione-S-transferases (GST)-α (suggestive of kidney damage at the level of PT) would be expected to be more related to Hg exposure than GST-π (suggestive of kidney damage at the level of the distal tubules). Urinary biomarkers of kidney integrity were examined in children of 8-18 years old, with and without dental amalgam fillings, from a completed clinical trial (parent study). Our study determined whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and GST-α and GST-π as biomarkers of kidney integrity. Overall, the present study, using a different and more sensitive statistical model than the parent study, revealed a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary levels of GST-α, after covariate adjustment; where as, a nonsignificant relationship was observed with urinary levels of GST-π. Furthermore, it was observed that urinary GST-α levels increased by about 10% over the 8-year course of the study among individuals with an average exposure to amalgams among the study subjects from the amalgam group, in comparison with study subjects with no exposure to dental amalgams. The results of our study suggest that dental amalgams contribute to ongoing kidney damage at the level of the PTs in a dose-dependent fashion.

Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in major depressive disorder.

Exercise is an efficacious treatment for major depressive disorder (MDD) and has independently been shown to have anti-inflammatory effects in non-depressed subjects. Patients with MDD have elevated inflammatory cytokines but it is not known if exercise affects inflammation in MDD patients and whether these changes are clinically relevant. In the TReatment with Exercise Augmentation for Depression (TREAD) study, participants who were partial responders to a selective serotonin reuptake inhibitor were randomized to receive one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW), or 4 KKW for 12 weeks. Blood samples were collected before initiation and again at the end of the 12-week exercise intervention. Serum was analyzed using a multiplexed ELISA for interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher baseline levels of TNF-α were associated with greater decrease in depression symptoms over the 12-week exercise period (P<0.0001). In addition, a significant positive correlation between change in IL-1ß and change in depression symptom scores was observed (P=0.04). There were no significant changes in mean level of any cytokine following the 12-week intervention, and no significant relationship between exercise dose and change in mean cytokine level. Results suggest that high TNF-α may differentially predict better outcomes with exercise treatment as opposed to antidepressant medications for which high TNF-α is linked to poor response. Our results also confirm findings from studies of antidepressant medications that tie decreasing IL-1ß to positive depression treatment outcomes.

Does exercise improve self-reported sleep quality in non-remitted major depressive disorder?

BACKGROUND: Sleep disturbances are persistent residual symptoms following remission of major depressive disorder (MDD) and are associated with an increased risk of MDD recurrence. The purpose of the current study was to examine the effect of exercise augmentation on self-reported sleep quality in participants with non-remitted MDD. Method Participants were randomized to receive selective serotonin reuptake inhibitor (SSRI) augmentation with one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). The four sleep-related items on the IDS-C (Sleep Onset Insomnia, Mid-Nocturnal Insomnia, Early Morning Insomnia, and Hypersomnia) were used to assess self-reported sleep quality. RESULTS: Significant decreases in total insomnia (p < 0.0001) were observed, along with decreases in sleep onset, mid-nocturnal and early-morning insomnia (p's <0.002). Hypersomnia did not change significantly (p = 0.38). Changes in total, mid-nocturnal and early-morning insomnia were independent of changes in depressive symptoms. Higher baseline hypersomnia predicted a greater decrease in depression severity following exercise treatment (p = 0.0057). No significant moderating effect of any baseline sleep on change in depression severity was observed. There were no significant differences between exercise treatment groups on total insomnia or any individual sleep item. CONCLUSIONS: Exercise augmentation resulted in improvements in self-reported sleep quality in patients with non-remitted MDD. Given the prevalence of insomnia as a residual symptom following MDD treatment and the associated risk of MDD recurrence, exercise augmentation may have an important role in the treatment of MDD.

Change in psychosocial functioning and depressive symptoms during acute-phase cognitive therapy for depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent, is recurrent, and impairs people's work, relationships and leisure. Acute-phase treatments improve psychosocial impairment associated with MDD, but how these improvements occur is unclear. In this study, we tested the hypotheses that reductions in depressive symptoms exceed, precede and predict improvements in psychosocial functioning. METHOD: Patients with recurrent MDD (n=523; 68% women, 81% Caucasian, mean age 42 years) received acute-phase cognitive therapy (CT). We measured functioning and symptom severity with the Social Adjustment Scale - Self-Report (SAS-SR), Range of Impaired Functioning Tool (RIFT), Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HAMD) and Inventory for Depressive Symptomatology - Self-Report (IDS-SR). We tested cross-lagged correlations between functioning and symptoms measured at baseline and the beginning, middle and end of acute-phase CT. RESULTS: Pre- to post-treatment improvement in psychosocial functioning and depressive symptoms was large and intercorrelated. Depressive symptoms improved more and sooner than did psychosocial functioning. However, among four assessments across the course of treatment, improvements in functioning more strongly predicted later improvement in symptoms than vice versa. CONCLUSIONS: Improvements in psychosocial functioning and depressive symptoms correlate substantially during acute-phase CT, and improvements in functioning may play a role in subsequent symptom reduction during acute-phase CT.

A dose-dependent relationship between mercury exposure from dental amalgams and urinary mercury levels: a further assessment of the Casa Pia Children's Dental Amalgam Trial.

Dental amalgams are a commonly used dental restorative material, and amalgams are about 50% mercury (Hg). In our study, urinary Hg levels was examined in children of age 8-18 years, with and without dental amalgam fillings, from a completed clinical trial (parent study) that was designed to evaluate the potential health consequences of prolonged exposure to Hg from dental amalgam fillings. Our study was designed to determine whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and urinary Hg levels. Hg exposure depends on the size and number of teeth with dental amalgams. Overall, consistent with the results observed in the parent study, there was a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary Hg levels, after covariate adjustment. Further, it was observed that urinary Hg levels increased by 18% to 52% among 8 to 18 year old individuals, respectively, with an average exposure to amalgams, in comparison to study subjects with no exposure to amalgams. The results of our study suggest that dental amalgams contribute to ongoing Hg exposure in a dose-dependent fashion.

Diagnostic utility of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16) in the elderly.

OBJECTIVE: To evaluate psychometric properties and comparability ability of the Montgomery-Asberg Depression Rating Scale (MADRS) vs. the Quick Inventory of Depressive Symptomatology-Clinician-rated (QIDS-C(16)) and Self-report (QIDS-SR(16)) scales to detect a current major depressive episode in the elderly. METHOD: Community and clinic subjects (age >or=60 years) were administered the Mini-International Neuropsychiatric Interview (MINI) for DSM-IV and three depression scales randomly. Statistics included classical test and Samejima item response theories, factor analyzes, and receiver operating characteristic methods. RESULTS: In 229 elderly patients (mean age = 73 years, 39% male, 54% current depression), all three scales were unidimensional and with nearly equal Cronbach alpha reliability (0.85-0.89). Each scale discriminated persons with major depression from the non-depressed, but the QIDS-C(16) was slightly more accurate. CONCLUSION: All three tests are valid for detecting geriatric major depression with the QIDS-C(16) being slightly better. Self-rated QIDS-SR(16) is recommended as a screening tool as it is least expensive and least time consuming.

Dyadic discord at baseline is associated with lack of remission in the acute treatment of chronic depression.

BACKGROUND: Dyadic discord, while common in depression, has not been specifically evaluated as an outcome predictor in chronic major depressive disorder. This study investigated pretreatment dyadic discord as a predictor of non-remission and its relationship to depressive symptom change during acute treatment for chronic depression. METHOD: Out-patients with chronic depression were randomized to 12 weeks of treatment with nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy or their combination. Measures included the Marital Adjustment Scale (MAS) and the Inventory of Depressive Symptomatology - Self Report (IDS-SR30). Of 681 original patients, 316 were partnered and 171 of these completed a baseline and exit MAS, and at least one post-baseline IDS-SR30. MAS scores were analysed as continuous and categorical variables ('dyadic discord' v. 'no dyadic discord' defined as an MAS score >2.36. Remission was defined as an IDS-SR30 of 14 at exit (equivalent to a 17-item Hamilton Rating Scale for Depression of 7). RESULTS: Patients with dyadic discord at baseline had lower remission rates (34.1%) than those without dyadic discord (61.2%) (all three treatment groups) (chi2=12.6, df=1, p=0.0004). MAS scores improved significantly with each of the treatments, although the change was reduced by controlling for improvement in depression. Depression remission at exit was associated with less dyadic discord at exit than non-remission for all three groups [for total sample, 1.8 v. 2.4, t(169)=7.3, p<0.0001]. CONCLUSIONS: Dyadic discord in chronically depressed patients is predictive of a lower likelihood of remission of depression. Couple therapy for those with dyadic discord may increase remission rates.

Anticipated Benefits of Care (ABC): psychometrics and predictive value in psychiatric disorders.

BACKGROUND: Attitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available. METHOD: The Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated. RESULTS: Evaluation of the ABC's internal consistency yielded Cronbach's alpha of 0.90-0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for all patients and for patients with each disorder. For patients with MDD, lower anticipated benefits of treatment was associated with less symptom improvement and lower odds of treatment response [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.87, p=0.0011]. There was no association between ABC and symptom improvement or treatment response for patients with bipolar disorder or schizophrenia, possibly because these patients had modest benefits with treatment. CONCLUSIONS: The ABC is the first self-report that measures patient expectations about the benefits of treatment on everyday functioning, filling an important gap in available assessments of attitudes and expectations about treatment. The ABC is simple, easy to use, and has acceptable psychometric properties for use in research or clinical settings.

The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation.

BACKGROUND: The present study provides additional data on the psychometric properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief 16-item symptom severity rating scale that was derived from the longer form. Both the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and self-report (IDS-SR30; QIDS-SR16) formats. METHOD: The patient samples included 544 out-patients with major depressive disorder (MDD) and 402 out-patients with bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses including sensitivity to change with treatment were conducted. RESULTS: Internal consistencies (Cronbach's alpha) ranged from 0.81 to 0.94 for all four scales (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad mood, involvement, energy, concentration and self-outlook had the highest item-total correlations among patients with MDD and BD across all four scales. QIDS-SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at exit (c = 0.83). QIDS-C16 and IDS-C30 total scores were also highly correlated among patients with MDD (c = 0.82) and patients with BD (c = 0.81). The IDS-SR30, IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change, indicating high concurrent validity for all four scales. High concurrent validity was also documented based on the SF-12 Mental Health Summary score for the population divided in quintiles based on their IDS or QIDS score. CONCLUSION: The QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly acceptable psychometric properties and are treatment sensitive measures of symptom severity in depression.

Onset and persistence of postpartum depression in an inner-city maternal health clinic system.

OBJECTIVE: Postpartum depressive disorders lead to maternal disability and disturbed mother-infant relationships, but information regarding the rates of major depressive disorder in minority women is noticeably lacking. The goal of this study was to determine whether the risk factors for and rate of postpartum major depressive disorder in a predominantly African American and Hispanic clinic population would be similar to those reported for Caucasian women. METHOD: Investigators systematically screened all women scheduled for their first postpartum visit on selected days at four publicly funded inner-city community maternal health clinics in Dallas County (N=802). A multistage screening process included the Edinburgh Postnatal Depression Scale, the Inventory of Depressive Symptomatology, and the Structured Clinical Interview for DSM-IV for a maximum of three assessments during the initial 3-5-week postpartum period. RESULTS: The estimated rate of major depressive disorder during the postpartum period among women in this setting was between 6.5% and 8.5%. Only 50% of the depressed women reported onset following birth. Bottle-feeding and not living with one's spouse or significant other were associated with depression at the first evaluation; persistent depressive symptoms were linked with the presence of other young children at home. Greater severity of depressive symptoms at first contact predicted major depressive disorder several weeks later. CONCLUSIONS: Rates of postpartum depression among Latina and African American postpartum women are similar to epidemiologic rates for Caucasian postpartum and nonpostpartum women. As previously shown for Caucasian women, major depressive disorder in many Latina and African American postpartum women begins before delivery, revealing the need to screen pregnant women for depression.

An analysis of reported deaths following electroconvulsive therapy in Texas, 1993-1998.

Since 1993, Texas law has required that all deaths that occur within 14 days of electroconvulsive therapy (ECT) be reported to the Texas Department of Mental Health and Mental Retardation. This study attempted to differentiate deaths that may have been due to ECT or the associated anesthesia from those due to other causes. Among more than 8,000 patients who received 49,048 ECT treatments between 1993 and 1998, a total of 30 deaths were reported to the mental health department between 1993 and 1998. Only one death, which occurred on the same day as the ECT, could be specifically linked to the associated anesthesia. An additional four deaths could plausibly have been associated with the anesthesia, for which the calculated mortality rate is between two and ten per 100,000, but probably not with the stimulus of the ECT or seizure. The mortality rate associated with ECT (less than two per 100,000 treatments) in Texas is extremely low.

Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline.

Our objective was to determine if pretreatment anxiety levels were associated with preferential response to bupropion sustained release (n = 122) or sertraline (n = 126) during a 16-week randomized acute phase treatment study. Both agents had comparable antidepressant activity, and comparable anxiolytic effects using the intent-to-treat sample. Baseline anxiety levels were not related to antidepressant efficacy, and they did not differentiate responders to each agent. Time to clinically significant anxiolysis did not differentiate between treatment groups or between responders to each agent. These results contradict the commonly held, but unsubstantiated, belief that in clinically depressed anxious patients, serotonergic antidepressants are especially anxiolytic and that such patients preferentially benefit from the antidepressant or anxiolytic effects of selective serotonin reuptake inhibitors. Thus, the clinical decision to select between these two agents when treating depressed outpatients cannot rest on either levels of pretreatment anxiety or on anticipation of more rapid or more complete anxiolysis.

Does pretreatment anxiety predict response to either bupropion SR or sertraline?

BACKGROUND: A common clinical belief is that more sedating and/or serotonin-selective antidepressants are preferred for depressed patients with symptoms of anxiety compared with more activating and/or catecholamine-selective antidepressants. The purpose of this study was to determine whether higher baseline anxiety is associated with different antidepressant responses to bupropion sustained release (SR) or sertraline. METHODS: A retrospective data analysis was conducted using pooled data from two identical 8-week, randomized, double-blind, placebo-controlled multicenter studies of bupropion SR (n=234), sertraline (n=225), and placebo (n=233) in adult outpatients with recurrent, major depressive disorder. Anxiety symptoms were measured using the 14-item Hamilton Anxiety Rating Scale scores. RESULTS: Baseline anxiety levels were not related to antidepressant response to treatment with either bupropion SR or sertraline, nor did they differentiate between responders to bupropion SR and responders to sertraline. CONCLUSIONS: Baseline anxiety levels do not appear to be a basis for selecting between bupropion SR and sertraline in the treatment of outpatients with major depressive disorder.

Severe delayed thrombocytopenia associated with abciximab (ReoPro) therapy.

Acute thrombocytopenia associated with abciximab therapy has been well described, although the exact mechanism remains obscure. We report a case of delayed severe thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention that occurred following hospital discharge. The detection of this phenomenon is important as it may portend heightened risk for severe or profound thrombocytopenia on subsequent reexposure to abciximab therapy.

Which depressed patients respond to nefazodone and when?

BACKGROUND: Retrospective data analyses were conducted of a single-blind trial of 993 outpatients with nonpsychotic major depression (DSM-III-R) treated for 12 weeks with nefazodone to provide a more specific picture of the nature and timing of response or remission to acute-phase treatment. METHOD: All patients participated in a single-blind, 16-week lead-in to obtain responders eligible for a subsequent double-blind, randomized continuation phase trial. Outcomes were defined by the 17-item Hamilton Rating Scale for Depression (HAM-D). A > or = 50% reduction from baseline defined response, and a total HAM-D exit score of < or =8 defined remission. RESULTS: Of all patients who entered the trial, 41.8% (last observation carried forward) responded at or before week 4 (early responders), and an additional 25.2% responded thereafter; 18.3% achieved remission at or before week 4; 33.6% achieved remission after week 4. Thus, 77.3% of those responding ultimately remitted. On average, remission followed response by 2 weeks. The average end-of-treatment dose was 376 mg/day at exit (last observation carried forward). Responders or remitters (as opposed to nonresponders or nonremitters) had lower baseline depressive symptomatology and were more likely to be married or cohabiting. CONCLUSION: The full symptomatic benefit of antidepressant medication may not be apparent until completion of an 8- to 10-week trial. A high number of responders ultimately attained remission. Baseline demographic and clinical features were not highly predictive of who would or would not benefit from nefazodone. For routine care, a minimal acute-phase trial, using a 50% reduction in baseline symptom severity to define response, should be 8 weeks. Whether ultimate nonresponders can be identified earlier than 8 weeks deserves further study.