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. In order to compare our findings with prior research, we focused primarily on outcomes at weeks 6, 8, and 12. RESULTS: The likelihood of converting to a positive response decreased the longer subjects remained unimproved. When week 6 was used as the end point, the likelihood of converting to a positive response for unimproved subjects at week 1 was 36% (n = 302); the respective conversion rates for weeks 2-5 were 29% (n = 208) at week 2, 18% (n = 151) at week 3, 17% (n = 120) at week 4, and 9% (n = 91) at week 5. When week 8 was used as the end point, the likelihood of converting to a positive response for unimproved subjects at week 4 was 23% (n = 118) and, at week 6, was 10% (n = 61). Finally, when week 12 was used as the end point, the likelihood of unimproved subjects at weeks 4, 6, and 8 converting to a positive response at week 12 was 50% (n = 117), 33% (n = 60), and 30% (n = 46), respectively. CONCLUSIONS: The study adds to a small, but growing literature that gives clinicians some guidelines to help decide whether to continue an antidepressant trial when little or no benefit has yet been observed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00427128.

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. Data were extracted with the use of a precoded form. Data from four clinical trials involving a total of 444 patients with MDD were identified and combined using a random effects model. There was no statistically significant difference in terms of remission rates or response rates at week 1, week 2, or at endpoint between the two treatment groups (SSRI+T3 coinitiation therapy vs. SSRI monotherapy). Pooled response and remission rates at endpoint for the SSRI+T3 versus SSRI monotherapy groups were 64.6 versus 58.5% and 46.8 versus 44.8%, respectively. In addition, there was no statistically significant difference in overall rates of premature discontinuation of treatment, or in the rate of premature discontinuation of treatment owing to inefficacy or intolerance between the two treatment groups. Notwithstanding important methodological differences between the studies included in the meta-analysis in terms of patient characteristics and treatment protocols, these results do not support the notion that simultaneous initiation of treatment of MDD with an SSRI and T3 is more effective than SSRI monotherapy. However, given the etiologically diverse and clinically heterogeneous nature of MDD, it is at least plausible that T3-SSRIs coinitiation therapy may be effective for a particular subgroup of patients including patients with atypical depression or patients with a functional polymorphism of the D-1 deiodinase gene. Clearly, further work is needed to help determine whether there are specific MDD populations that can, indeed, benefit from T3-SSRI coinitiation therapy.

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). The CUDOS was designed to be brief (completed in less than 3 minutes), quickly scored (in less than 15 seconds), clinically useful (fully covering the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition symptoms of major depressive disorder and dysthymic disorder), reliable, valid, and sensitive to change. We studied the CUDOS in more than 1400 psychiatric outpatients and found that the scale had high internal consistency and test-retest reliability. The CUDOS was more highly correlated with another self-report measure of depression than with measures of anxiety, substance use problems, eating disorders, and somatization, thereby supporting the convergent and discriminant validity of the scale. The CUDOS was also highly correlated with interviewer ratings of the severity of depression, and CUDOS scores were significantly different in depressed patients with mild, moderate, and severe levels of depression. The CUDOS was a valid measure of symptom change. Finally, the CUDOS was significantly associated with a diagnosis of major depressive disorder. Thus, the results of this large validation study of the CUDOS shows that it is a reliable and valid measure of depression that is feasible to incorporate into routine clinical practice.

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. Recovery was defined as at least eight consecutive weeks with either no symptoms of major depression, or only one or two symptoms at a mild level of severity. RESULTS: In the mixed-effects model, a one standard deviation increase in psychosocial impairment was significantly associated with a 22% decrease in the likelihood of subsequent recovery from an episode of major depression (OR=0.78, 95% CI: 0.74-0.82, Z=-3.17, p<0.002). Also, a one standard deviation increase in cumulative morbidity was significantly associated with a 61% decrease in the probability of recovery (OR=0.3899, 95% CI: 0.3894-0.3903, Z=-7.21, p<0.001). LIMITATIONS: The generalizability of the study is limited in so far as subjects were recruited as they sought treatment at academic medical centers. The analyses examined the relationship between psychosocial functioning and recovery from major depression, and did not include episodes of minor depression. Furthermore, this was an observational study and the investigators did not control treatment. CONCLUSIONS: Assessment of psychosocial impairment may help identify patients less likely to recover from an episode of major depression.

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. These side effects often create barriers to achieving depressive remission, as well as to preventing relapse and recurrence. Clinicians tend to underestimate the prevalence of side effects, and as many as one quarter of patients discontinue their antidepressants because of difficult-to-tolerate side effects; others may continue on antidepressant therapy but experience diminished quality of life related to troublesome side effects. This article reviews the prevalence of side effects, the impact of side effects on treatment adherence, and methodological issues including the challenge of distinguishing side effects from residual depressive symptoms, discontinuation effects, and general medical problems. In addition, we address the most common side effects such as sexual dysfunction, gastrointestinal problems, sleep disturbance, apathy and fatigue, and offer strategies for management that may help patients achieve optimal response to pharmacotherapy

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. A positive response was defined as a > or = 50% reduction in Montgomery-Asberg Depression Rating Scale scores. Response rates were higher for the adjunctive T3 cohort compared to the adjunctive placebo cohort after 1 wk (45% vs. 24%) and 2 wk (57% vs. 33%) of treatment. The likelihood of experiencing a positive response at any point over the 6-wk trial was 4.5 times greater in the adjunctive T3 cohort (95% CI 1.3-15.7). The study provides preliminary evidence that T3 can successfully be used in clinical practice to accelerate the antidepressant response and improve overall outcomes. The effectiveness model may be an untapped mechanism for evaluating the value of psychopharmacological agents.

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. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined the independent and additive association between level of severity of depressive symptoms and functional impairment in predicting depressed patients' subjective evaluation of their remission status. METHODS: Five hundred and fourteen depressed psychiatric outpatients filled out a questionnaire on which they rated the severity of the symptoms of depression, the level of impairment due to depression, and their quality of life. RESULTS: Symptom severity, functional impairment from depression, and quality of life were significantly and highly intercorrelated, and each was significantly associated with remission status. The results of a logistic regression analysis indicated that each of the three variables was a significant, independent, predictor of remission status. DISCUSSION: In treatment studies of depression remission is narrowly defined in terms of symptom resolution. Our results support broadening the concept of remission beyond symptom levels to include assessments of functioning and quality of life.

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. Included studies (n=41) were divided into those that conducted four, five or six follow-up assessments. Reductions in HRSD scores as a function of the different follow-up schedules were compared. RESULTS: An extra follow-up visit at week 3 was associated with a 0.86 further reduction in HRSD score; an extra visit at week 5 was associated with a 0.67 further reduction. These effects represented approximately 34-44% of the placebo response that occurred over these time frames. Two additional visits were associated with twice the reduction in HRSD score than one, suggesting that the therapeutic impact of assessment visits is cumulative and proportional. A comparable therapeutic effect was also found in participants receiving active medication. CONCLUSIONS: Follow-up assessments in antidepressant treatment trials incur a significant therapeutic effect for participants on placebo, and this represents about 40% of the placebo response.

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. We hypothesized that the design of antidepressant continuation studies would impact on the likelihood of relapse. In the extension design, there is no change in treatment. Whether patients responded to placebo or medication, the treatment that produced the response is continued. In contrast, in the placebo substitution design, there is an obvious change in treatment protocol upon initiation of the continuation phase. Patients are aware that they initially received active medication, and there is now a chance that they will be switched to placebo. We speculated that the expectation of a continued positive response is lower in patients treated using the placebo substitution design than the extension design and therefore predicted that relapse rates would be higher. We conducted a meta-analysis of antidepressant continuation studies and compared the relapse rates in continuation studies using these 2 different designs. As predicted, for both the active medication and placebo groups, the frequency of relapse was lower in studies using an extension design. We also found that the difference in relapse risk between antidepressants and placebo was greater with the extension design. Thus, the design of continuation studies of antidepressants was associated with the absolute percentage of patients who relapse on both active medication and placebo, as well as estimates of differential relapse risk between antidepressants and placebo.

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. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined whether there is heterogeneity within the group of patients that are typically classified as remitters. Three hundred three depressed psychiatric outpatients were rated on the Standardized Clinical Outcome Rating for Depression, an index of Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition remission status, and the 17-item HAM-D. Approximately half of the patients completed a measure of psychosocial impairment. Treatment responders were divided into 2 groups, remitters (HAM-D < or =7) and nonremitters (HAM-D > or =8). The treatment remitters were further subdivided into 2 groups, remitters with and without mild residual symptoms (HAM-D 3-7 vs 0-2). We refer to these 3 nonoverlapping groups as responders, partial remitters (ie, remitters with mild residual symptoms), and full remitters (remitters without residual symptoms). Responders scored statistically significantly higher, indicating greater psychosocial impairment, than the entire group of remitters, and the partial remitters scored significantly higher than the full remitters. Among the responders, the correlation between remission status and functioning was -.49 (P < .01). Among the remitters, the correlation between residual symptom status and functioning was nearly as high (-.42, P < .05). These results suggest that there is as much heterogeneity among patients who are typically considered to be in remission as there is among responders. This supports recommendations to lower the cutoff on the HAM-D to define remission.

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. Consequently, we developed and determined the reliability and validity of ultra-brief, single-item assessments of 3 domains important to consider when treating depressed patients: symptom severity, psychosocial functioning, and quality of life. METHOD: In the first study (conducted June 1997 to March 2002), 1278 psychiatric outpatients with various DSM-IV diagnoses completed single-item assessments of psychosocial functioning and quality of life as well as more detailed measures of these constructs. In the second study (conducted August 2003 to July 2004), 562 psychiatric outpatients who were in ongoing treatment for a DSM-IV major depressive episode completed a depression symptom scale and a measure of global severity of depression. RESULTS: The test-retest reliability of the psychosocial functioning and quality-of-life items was high. The single-item measures of symptom severity, psychosocial functioning, and quality of life were significantly correlated with the total scores and individual item scores of longer measures of the same constructs (p < .001). The single-item measures significantly discriminated between depressed patients in full remission, in partial remission, and in a current depressive episode (p < .001). CONCLUSION: These studies provide evidence of the reliability and validity of single-item measures of symptom severity, psychosocial functioning, and quality of life. Very brief measures, such as the ones described in the present report, are not burdensome for patients to complete and can be easily incorporated into a busy clinical practice in order to collect data on treatment effectiveness.

The impact of gender, age and depressed state on patients' perspectives of remission.

BACKGROUND: Current standards for treatment outcome from major depression assess remission solely from the vantage point of symptom resolution. Recent evidence, however, suggests that depressed patients consider factors beyond symptom resolution as important for defining remission. The goal of this study was to examine the influence of three predictors on patients' views of factors important for achieving remission: gender, age and current depressed state (i.e., remitted or depressed). METHODS: Five hundred and sixty-two depressed psychiatric outpatients completed a survey assessing the importance of 16 remission factors. Depressed state was assessed by the Standardized Clinical Outcome Rating scale for Depression (SCOR-D), a clinician rated scale that is based on the number of DSM-IV criteria for a major depressive episode and level of psychosocial impairment present during the past week. RESULTS: Relative to male patients, females showed a greater likelihood for rating remission factors related to emotional stabilization (e.g., achieving emotional control, being able to cope with normal stress) as very important. Relative to younger cohorts, the oldest depressed patients endorsed a greater number of remission factors as very important and emphasized positive mental health states (e.g., feeling satisfied, having a general sense of well-being) more. There were no significant differences between remitted and depressed patients in rating the remission factors' importance. CONCLUSION: Perspectives on remission may be differentially perceived by women versus men and by older versus younger depressed patients. LIMITATIONS: The study was conducted in a single outpatient clinical practice.

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. The duration of the recurrent episode was examined using survival analytic techniques. Of the 130 subjects, 46 obtained somatic therapy at some time during the course of their depressive illness, while 84 subjects received no somatic therapy throughout their entire depressive episode. Survival analysis, which accounts for these 46 individuals by censoring their episodes at the time treatment was obtained, yielded a median time to recovery of 23 weeks. In the subsample of 84 subjects whose depressive illness went untreated from its inception through its resolution, the median time to recovery was 13 weeks. These results suggest that there is a high rate of recovery in individuals not receiving somatic treatment of their depressive illness, particularly in the first 3 months of an episode. Because treatment-seeking behavior is known to be associated with a worse prognosis, 23 weeks probably represents a lower-limit approximation of the median duration of an untreated depressive episode.

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. In a previous report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we derived a cutoff on a self-report depression questionnaire corresponding to the widely used definition of remission on the HRSD (ie, < or = 7). In the present report, we examined the validity of this questionnaire as an indicator of remission among patients who responded to antidepressant treatment. Specifically, we examined psychosocial functioning in treatment responders who were and were not in remission according to the self-report symptom scale. In a sample of 371 depressed outpatients who were judged by their treating psychiatrists as having responded to treatment, 250 scored in the remission range on the symptom scale. Compared with treatment responders whose depression was not in remission, the patients who were in remission reported significantly less psychosocial impairment and significantly better quality of life and were significantly more likely to assert that they are in remission from their depression. These findings support the validity of a self-report depression questionnaire as an index of remission status among treatment responders.

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. Rather, in treatment studies of depression, remission has been defined in symptom terms only. Clinical experience suggests that there is sometimes discordance between patients' symptom severity and functioning. No studies, however, have examined the frequency of this discordance. We examined the concordance of ratings of depression symptom severity and psychosocial functioning in a sample of 503 outpatients receiving treatment for major depressive disorder. The majority of patients were concordant in these ratings (i.e. no symptoms and no functional impairment, or ongoing symptoms and impairment), though one quarter of the patients were discordant. Specifically, approximately one quarter of the patients with depressive symptoms denied concurrent psychosocial impairment. In contrast, it was rare for patients without symptoms to report functional impairment. Almost all patients without both symptoms and functional impairment considered themselves to be in remission, and almost all patients with both symptoms and functional impairment did not consider themselves to be in remission. Half of the patients who reported normal functioning despite ongoing depressive symptoms considered themselves to be in remission from their depression. This suggests that current symptom-based definitions of remission might be too narrow.

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. The authors' goal was to determine what depressed patients consider important in defining remission from depression. METHOD: A brief questionnaire was distributed to 535 psychiatric outpatients who were being treated for DSM-IV major depressive episode. They were asked to rate the importance of 16 statements in determining whether depression is in remission. RESULTS: The three items most frequently judged to be very important in determining remission were the presence of features of positive mental health such as optimism and self-confidence; a return to one's usual, normal self; and a return to usual level of functioning. The patients endorsed a statement about absence of symptoms with nearly similar frequency. CONCLUSIONS: Patients aspire to a range of outcomes from the treatment of their depression.

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., underwent structured diagnostic assessment for Axis I and II disorders. The diagnosis of IED was made according to DSM-IV criteria. RESULTS: 6.3% (SE, +/- 0.7%) of patients met criteria for lifetime DSM-IV IED, and 3.1% +/- 0.5% of patients met criteria for current DSM-IV IED. While DSM-IV IED was the current principal diagnosis in only 0.6% +/- 0.2% of patients, most patients with current DSM-IV IED (80%) were interested in treatment for their intermittent aggressive behavior. Only lifetime alcohol/drug disorder was more frequent in DSM-IV IED compared with non-IED patients. Age at onset for DSM-IV IED peaked in the teen years, was earlier for men than women, and occurred earlier than all comorbid disorders, with the exception of phobic anxiety disorders, suggesting that IED cannot be attributed to most comorbid conditions. CONCLUSIONS: DSM-IV IED in psychiatric samples is far more common than previously thought. DSM-IV IED develops early in life, especially in male patients, and its development may be independent of most other disorders.

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). However, recent research has suggested that use of this cutoff on the HAM-D to define remission is overinclusive. The goal of the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project was to examine how many depressed patients in ongoing treatment who are considered to be in remission by a self-report equivalent of the HAM-D definition of remission nonetheless do not consider themselves to be in remission. METHOD: Five hundred thirty-five psychiatric outpatients treated for a DSM-IV major depressive episode were asked whether they considered themselves to be in remission and completed the Clinically Useful Depression Outcome Scale (CUDOS), a measure of the severity of the DSM-IV symptoms of depression. The study was conducted from August 2003 until July 2004. RESULTS: Nearly one quarter of the patients who met the remission threshold on the CUDOS (55/249) did not consider themselves to be in remission. Among the CUDOS remitters, the total score on the CUDOS was significantly lower (p < .001) in patients who considered themselves to be in remission than in patients who did not indicate that they were in remission. Examination of specific symptoms revealed greater appetite disturbance and hypersomnia in the patients who did not think they were in remission. CONCLUSIONS: Our results suggest that heterogeneity of clinical status exists even among patients who are minimally depressed and considered to be in remission according to contemporary definitions on symptom severity scales.

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. MATERIALS AND METHODS: Psychiatrists from 2 academic sites reviewed charts of patients on their caseloads. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales were used to measure severity of depression and response to treatment, and 2 treatment-resistant staging scores were classified for each patient using the Massachusetts General Hospital staging method (MGH-S) and the Thase and Rush staging method (TR-S). RESULTS: Out of the 115 patient records reviewed, 58 (49.6%) patients remitted at some point during treatment. There was a significant positive correlation between the 2 staging scores, and logistic regression results indicated that greater MGH-S scores, but not TR-S scores, predicted nonremission. CONCLUSIONS: This study suggests that the hierarchical manner in which the field has typically gauged levels of treatment resistance may not be strongly supported by empirical evidence. This study suggests that the MGH staging model may offer some advantages over the staging method by Thase and Rush, as it generates a continuous score that considers both number of trials and intensity/optimization of each trial.