Response rates to fluoxetine in subjects who initially show no improvement.

Objective: This study sought to investigate the likelihood that subjects will respond to continued antidepressant therapy when little or no benefit has yet been observed.

Method: Six hundred twenty-seven subjects diagnosed with DSM-IV major depressive disorder were recruited in a 12-week open-label trial with fluoxetine, which was designed as a preliminary phase to a subsequent 52-week continuation trial, which was conducted in 1997-2003. For each week of the study, a calculation was made for all subjects who had heretofore demonstrated little or no improvement as to the likelihood of converting to a positive response in subsequent weeks as measured by the Clinical Global Impressions scale, the primary outcome measure.

Toward achieving optimal response: understanding and managing antidepressant side effects.

The safety and tolerability of antidepressants have improved considerably over the past two decades. Nevertheless, antidepressant side effects are still common and problematic. The majority of patients treated with contemporaty agents experience one or more bothersome side effects.

Simultaneous initiation (coinitiation) of pharmacotherapy with triiodothyronine and a selective serotonin reuptake inhibitor for major depressive disorder: a quantitative synthesis of double-blind studies.

To examine the efficacy and overall tolerability of the simultaneous initiation of treatment (coinitiation) with triiodothyronine (T3) and a selective serotonin reuptake inhibitor (SSRI) for major depressive disorder (MDD). Sources of date were Medline/Pubmed, EMBASE, the Cochrane database, and program syllabi from major psychiatric meetings held since 1995. The study selection comprised double-blind, randomized clinical trials comparing T3-SSRI coinitiation therapy versus SSRI monotherapy for MDD.

A clinically useful depression outcome scale.

If the optimal delivery of mental health treatment ultimately depends on examining outcome, then precise, reliable, valid, informative, and user-friendly measurement is the key to evaluating the quality and efficiency of care in clinical practice. Self-report questionnaires are a cost-effective option because they are inexpensive in terms of professional time needed for administration, and they correlate highly with clinician ratings. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we describe the reliability and validity of the Clinically Useful Depression Outcome Scale (CUDOS).

Remission in depressed outpatients: more than just symptom resolution?

Objective: In treatment studies of depression remission is defined according to scores on symptom severity scales. Normalization of functioning has often been mentioned as an important component of the definition of remission, though it is not used to identify remitted patients in studies of treatment efficacy. Conceptually, the return of normal functioning should be as fundamental to the concept of remission as is symptom resolution because the presence of both symptoms and impaired functioning are core constructs in the diagnosis of mental disorders.

Predicting recovery from episodes of major depression.

Background: This study examined psychosocial functioning as a predictor of recovery from episodes of unipolar major depression.

Methods: 231 subjects diagnosed with major depressive disorder according to Research Diagnostic Criteria were prospectively followed for up to 20 years as part of the NIMH Collaborative Depression Study. The association between psychosocial functioning and recovery from episodes of unipolar major depression was analyzed with a mixed-effects logistic regression model which controlled for cumulative morbidity, defined as the amount of time ill with major depression during prospective follow-up.

Impact of study design on the results of continuation studies of antidepressants.

Antidepressant continuation studies have used 2 different designs. In the placebo substitution design, all patients are initially treated with active medication in an open-label fashion, and then treatment responders are randomized to continue with medication or switch to placebo in a double-blind manner. In the extension design, patients are randomized to a double-blind placebo-controlled acute study at the outset, and responders to active treatment and placebo are continued on the treatment to which they initially responded.

Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials: meta-analysis.

Background: It remains unclear how much various factors contribute to the placebo response.

Aims: To estimate the therapeutic impact of follow-up assessments on placebo response in antidepressant trials.

Method: Double-blind, placebo-controlled antidepressant trials that reported weekly changes in Hamilton Rating Scale for Depression (HRSD) scores over 6 weeks were selected.

A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response.

The aim was to evaluate whether adjunctive T3 can help accelerate the antidepressant response and improve overall outcomes when used under naturalistic conditions. Fifty consecutive psychiatric outpatients diagnosed with major depressive disorder who were initiated on antidepressant therapy were randomized to receive adjunctive T3 or placebo in a double-blind manner over the course of 6 wk. There were no restrictions placed on the selection of antidepressant agent, dosing, ancillary medications, or psychotherapy, and there were few exclusion criteria.

Heterogeneity among depressed outpatients considered to be in remission.

More than a decade ago, a consensus panel recommended that remission be defined on the 17-item version of the Hamilton Rating Scale for Depression (HAM-D) as a cutoff of less than 7. Recently, some investigators have suggested that this threshold to define remission may be too high. If true, this means that heterogeneity exists within the group of treatment remitters accounting for variance in psychosocial function and relapse risk.

Developing brief scales for use in clinical practice: the reliability and validity of single-item self-report measures of depression symptom severity, psychosocial impairment due to depression, and quality of life.

Objective: Reliable, valid, user-friendly measurement is necessary to successfully implement an outcomes evaluation program in clinical practice. Self-report questionnaires, which generally correlate highly with clinician ratings, are a cost-effective assessment option. However, even self-administered questionnaires can be burdensome to patients because many are lengthy.

The naturalistic course of unipolar major depression in the absence of somatic therapy.

The goal of the study was to describe the naturalistic course of unipolar major depression in subjects not receiving somatic therapy for their depressive illness. Affectively ill individuals were recruited into the Collaborative Depression Study and followed prospectively for up to 15 years. One hundred thirty subjects who recovered from their intake episode of major depression subsequently experienced a recurrence that went untreated for at least 4 weeks following onset of the recurrence.

Validity of a self-report depression symptom scale for identifying remission in depressed outpatients.

In treatment studies of depression, remission is usually defined by scoring less than a threshold value on an interview-based measure of depression severity such as the Hamilton Rating Scale for Depression (HRSD). Although it has been recommended that measures such as the HRSD be used by clinicians in clinical practice to evaluate remission status, the time demands of clinical practice limit the feasibility of this suggestion. Self-report questionnaires are a cost-effective option to thoroughly, systematically, reliably, and validly evaluate clinical status because they are inexpensive in terms of professional time needed for administration and do not require special training for administration.

Discordance between self-reported symptom severity and psychosocial functioning ratings in depressed outpatients: implications for how remission from depression should be defined.

The diagnosis of depression is based on the presence of symptoms along with functional impairment. One might therefore expect the definition of remission of depressive disorder to be based on the resolution of both symptoms and functional impairments. This, however, is not how the field has been defining remission.

A description of next-step switching versus augmentation practices for outpatients with treatment-resistant major depressive disorder enrolled in an academic specialty clinic.

Background: There is a paucity of naturalistic studies from depression specialty clinics describing the next-step (augmentation versus switching) practices of clinicians for outpatients with major depressive disorder (MDD) resistant to an antidepressant trial of adequate dose and duration.

Methods: Eighty-five MDD outpatients enrolled in one of two specialty clinics, who had not achieved remission after a first adequate prospective antidepressant trial conducted at the clinic underwent either augmentation (n = 36) or switching (n=49) of their antidepressant regimen. Outcome was defined with the use of the Clinical Global Impressions (CGI) Scale.

How should remission from depression be defined? The depressed patient's perspective.

Objective: Although experts in the treatment of depression have suggested that achieving remission is the primary goal of treatment, questions remain about how remission should be defined. In antidepressant efficacy trials, remission is defined according to scores on symptom severity scales. Normalization of functioning is often mentioned as an important component of remission, although it is not used to identify patients with remission in treatment studies.

Prevalence and features of intermittent explosive disorder in a clinical setting.

Objective: To determine the lifetime and current prevalence, along with other characteristics such as age at onset, patterns of comorbidity, and interest in treatment, of DSM-IV intermittent explosive disorder (IED) in an outpatient psychiatric sample.

Method: 1300 individuals presenting for outpatient psychiatric treatment at Rhode Island Hospital, Providence, R.I.

Differences between minimally depressed patients who do and do not consider themselves to be in remission.

Objective: We recently derived a cutoff on a self-report scale corresponding to the most commonly used definition of remission in depression treatment studies (i.e., Hamilton Rating Scale for Depression [HAM-D] score < or = 7).

Empirical testing of two models for staging antidepressant treatment resistance.

Background: An increasing amount of attention has been paid to treatment resistant depression. Although it is quite common to observe nonremission to not just one but consecutive antidepressant treatments during a major depressive episode, a relationship between the likelihood of achieving remission and one's degree of resistance is not clearly known at this time. This study was undertaken to empirically test 2 recent models for staging treatment resistance.

Dual reuptake inhibitors incur lower rates of tachyphylaxis than selective serotonin reuptake inhibitors: a retrospective study.

Background: The notion that selective serotonin reuptake inhibitors (SSRIs) may be associated with higher relapse rates than other antidepressants during maintenance treatment (tachyphylaxis) has been discussed for years, but to date there is little or no empirical evidence confirming this phenomenon. In this study, we systematically assessed prior anti-depressant treatment history in a cohort of depressed patients who presented for outpatient psychiatric treatment. Rates of tachyphylaxis were compared in venlafaxine and tricyclic antidepressants (TCAs), which act as dual reuptake inhibitors, versus SSRIs.

Why isn't bupropion the most frequently prescribed antidepressant?

Objective: Reviews of antidepressant medication efficacy suggest that all antidepressants are equally effective. Bupropion is less likely than other antidepressants to cause weight gain and sexual dysfunction, the 2 side effects that are of greatest concern to patients and that have the greatest impact on long-term compliance. If bupropion is as effective as other antidepressants, and it does not cause the side effects that are the most frequent causes of long-term noncompliance, then why isn't it the most frequently prescribed antidepressant medication? To understand psychiatrists' decision making at the time an antidepressant is chosen, we conducted the Rhode Island Factors Associated With Antidepressant Choice Survey (FAACS).

Standardized clinical outcome rating scale for depression for use in clinical practice.

The integration of research into clinical practice to conduct effectiveness studies faces multiple obstacles. One obstacle is the burden of completing research measures of outcome. A simple, reliable, and valid measure that could be rated at every visit, incorporated into a clinician's progress note, and reflect the DSM-IV definition of a major depressive episode (including partial and full remission from the episode) would enhance the ability to conduct effectiveness research.

Tachyphylaxis in unipolar major depressive disorder.

Background: Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis.

Method: The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders.