Clinically Significant Changes in the 17- and 6-Item Hamilton Rating Scales for Depression: A STAR*D Report.

OBJECTIVE: To develop clinically meaningful improvement thresholds in both the 17-item and the 6-item Hamilton Rating Scale for Depression (HRSD) total scores in depressed outpatients. METHODS: The post-hoc analysis included all adult outpatients with non-psychotic major depressive disorder in the STAR*D trial who entered and exited the first treatment step (up to 14 weeks of citalopram) with a complete set of study measures at baseline and exit and at least one post-baseline measure. Within-patient change and linear regression anchor-based analyses were conducted to define meaningful and substantial changes in the HRSD17 and HRSD6 using three patient-reported outcomes [Work and Social Adjustment Scale (WSAS), Quality of Life Enjoyment and Satisfaction-Short Form (Q-LES-Q-SF); Mini-Q-LES-Q] obtained at baseline and exit from the first treatment step in STAR*D. RESULTS: Linear regression analyses identified a meaningful change threshold for the HRSD17 as 3.9 [3.7-4.1] [lower, upper 95% CI] and a substantial change as 7.8 [7.4-8.3] with the WSAS. Analogous thresholds based on the Q-LES-Q-SF were 5.8 [5.5-6.1] and 11.6 [11.0-12.2], respectively, and 4.9 [4.7-5.2] and 9.9 [9.3-10.4] for the Mini-QLES-Q, respectively. For the HRSD6, linear regression analyses with the WSAS identified a meaningful change as 2.2 [2.1-2.4], while a substantial change was 4.5 [4.2-4.7]. Analogous figures based on the Q-LES-Q-SF were 3.2 [3.0-3.4] and 6.4 [6.1-6.8]. Similarly, based on the Mini-QLESQ, results were 2.8 [2.6-2.9] and 5.6 [5.3-5.9]. For both the HRSD17 and the HRSD6, within-patient analyses produced less precise estimates of the same change thresholds with substantial overlap between groups. Based on the WSAS, a clinically meaningful change in the HRSD17 total score was 9.6 (SD = 6.5), while a substantial change was 15.0 (SD = 6.7). Analogous change thresholds based on the Q-LESQ-SF were 12.9 (SD = 6.2) and 16.8 (SD = 6.4), respectively. For the Mini-Q-LES-Q, thresholds were 10.9 (SD = 6.5) and 16.1 (SD = 6.2). CONCLUSION: A 4-6 point change in the HRSD17 is clinically meaningful; a 7-12 point change is clinically substantial. For the HRSD6, analogous estimates were 2-3 and 4-7 point changes, respectively.

Delayed quadriparesis after posterior spinal fusion for scoliosis: a case series.

STUDY DESIGN: A multicenter retrospective IRB exempt case series analyzing clinical and radiographical data of patients treated by three surgeons over the past two decades was conducted. OBJECTIVE: To examine the factors involved in the development of quadriparesis in patients who underwent posterior spinal fusion for scoliosis. Delayed spinal cord infarcts usually present at the region of instrumentation according to reports from the Scoliosis Research Society. Nonetheless, there is a lack of data regarding factors associated with delayed quadriparesis following posterior spinal fusion METHODS: Evaluated variables were age, Cobb angle, blood loss, and curve correction percentage. Postoperative imaging was also evaluated to determine factors indicative of the etiology of the quadriparesis. RESULTS: Eight patients presented delayed postoperative quadriparesis. All patients had a postoperative examination equal to that of baseline. The first patient deteriorated at 6 h postoperatively and the most delayed patient presented 4 days postoperatively. Six patients had neuromuscular disorders and 2 had adolescent idiopathic scoliosis. Mean age was 13.7, mean curve magnitude was 78.7°, mean percent curve correction was 71% and the mean estimated blood loss was 1185 cc. Seven of eight patients had documented peri- or postoperative hypotension. CONCLUSIONS: Cervical infarction is the likely cause of delayed quadriparesis after posterior spinal fusion. Even though the underlying etiology continues to be unclear, postoperative hypotension, curve magnitude, percent curve correction, and the presence of cervical kyphosis/stenosis may be contributory and need to be closely evaluated. LEVEL OF EVIDENCE: IV, Case Series.

The Concise Health Risk Tracking-Self Report: Psychometrics within a placebo-controlled antidepressant trial among depressed outpatients.

BACKGROUND/AIMS: While substantial prior research has evaluated the psychometric properties of the 12-item Concise Health Risk Tracking-Self Report (CHRT-SR12), a measure of suicide propensity and suicidal thoughts, no prior research has investigated its factor structure, sensitivity to change over time, and other psychometric properties in a placebo-controlled trial of antidepressant medication, nor determined whether symptoms change throughout treatment. METHODS: Participants in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study ( n=278) provided data to evaluate the factor structure and sensitivity to change over time of the CHRT-SR12 through eight weeks of a clinical trial in which participants received either placebo or antidepressant medication (sertraline). RESULTS/OUTCOMES: Factor analysis confirmed two factors: propensity (comprised of first-order factors including pessimism, helplessness, social support, and despair) and suicidal thoughts. Internal consistency (α's ranged from 0.69-0.92) and external validity were both acceptable, with the total score and propensity factor scores significantly correlated with total scores and single-item suicidal-thoughts scores on the self-report Quick Inventory of Depressive Symptoms and the clinician-rated 17-item Hamilton Rating Scale for Depression. Through analyzing CHRT-SR12 changes over eight treatment weeks, the total score and both the factors decreased regardless of baseline suicidal thoughts. Change in clinician-rated suicidal thoughts was reflected by change in both the total score and propensity factor score. CONCLUSIONS/INTERPRETATION: These results confirm the reliability, validity, and applicability of the CHRT-SR12 to a placebo-controlled clinical trial of depressed outpatients receiving antidepressant medication.

Difficult-to-treat depression: A clinical and research roadmap for when remission is elusive.

OBJECTIVES: The report considers the pros and cons of the most commonly used conceptual model that forms the basis for most clinical practice guidelines for depression. This model promotes the attainment of sustained symptom remission as the treatment goal based on its well-established prognostic and functional importance. Sustained remission is very unlikely, however, after multiple treatment attempts. Our current model propels many clinicians to continue to change or add treatments despite little chance for remission or full functional restoration and despite the increasing risk of more adverse events from polypharmacy. An alternative 'difficult-to-treat depression' model is presented and considered. It accepts that the treatment aims for some depressed patients may shift to optimal symptom control rather than remission. When difficult-to-treat depression is suspected, the many treatable causes of persistent depression must be assessed and addressed (given the importance of remission when attainable) before difficult-to-treat depression can be ascribed. The clinical and research implications of the difficult-to-treat depression model are discussed. CONCLUSION: Suspected difficult-to-treat depression provides a practical basis for considering when to conduct a comprehensive evaluation. Once difficult-to-treat depression is confirmed, treatment may better focus on optimal disease management (symptom control and functional improvement).

Early Improvement in Psychosocial Function Predicts Longer-Term Symptomatic Remission in Depressed Patients.

The goal of this study was to evaluate the relationship between early change in psychosocial function independent of depression severity and longer-term symptomatic remission. Participants of Combining Medications to Enhance Depression Outcomes trial were randomly selected for model selection (n = 334) and validation (n = 331). Changes in psychosocial function (Work and Social Adjustment Scale, WSAS) from baseline to week 6 were assessed and two data-driven sub-groups of WSAS change were identified in the randomly selected model selection half. Results of analyses to predict symptomatic remission at 3 and 7 months were validated for these sub-groups in the second half (validation sample). From baseline to week 6, psychosocial function improved significantly even after adjusting for depression severity at each visit and select baseline variables (age, gender, race, ethnicity, education, income, employment, depression onset before age 18, anxious features, and suicidal ideation), treatment-arm, and WSAS score. The WSAS change patterns identified two (early improvement and gradual change) subgroups. After adjusting for baseline variables and remission status at week 6, participants with early improvement in the second half (validation sample) had greater remission rates than those with gradual change at both 3 (3.3 times) and 7 months (2.3 times) following acute treatment initiation. In conclusion, early improvement in psychosocial function provides a clinically meaningful prediction of longer-term symptomatic remission, independent of depression symptom severity.

Prognostic Utility of a Self-Reported Depression Questionnaire versus Clinician-Based Assessment on Renal Outcomes.

BACKGROUND: The prognostic utility of self-administered depression scales in chronic kidney disease (CKD) independent of a clinician-based major depressive disorder (MDD) diagnosis is neither clearly established nor are the optimal cutoff scores for predicting outcomes. The overlap between symptoms of depression and chronic disease raises the question of whether a cutoff score on a depression scale can be substituted for a time-consuming diagnostic interview to prognosticate risk. METHODS: The 16-item Quick Inventory of Depression Symptomatology-Self Report scale (QIDS-SR16) was administered to 266 consecutive outpatients with non-dialysis CKD, followed prospectively for 12 months for an apriori composite outcome of death or dialysis or hospitalization. Association of QIDS-SR16 best cutoff score, determined by receiver/responder operating characteristics curves, with outcomes was investigated using survival analysis. The effect modification of an interview-based clinician MDD diagnosis on this association was ascertained. RESULTS: There were 126 composite events. A QIDS-SR16 cutoff ≥8 had the best prognostic accuracy, hazards ratio (HR) = 1.77, 95% CI 1.24-2.53, p = 0.002. This cutoff remained significantly associated with outcomes even after controlling for comorbidities, estimated glomerular filtration rate, hemoglobin and serum albumin, adjusted HR (aHR) = 1.80, 95% CI 1.23-2.62, p = 0.002, and performed similarly to a clinician-based MDD diagnosis (aHR = 1.72, 95% CI 1.14-2.68). Adjustment for MDD conferred the association of QIDS-SR16 with outcomes no longer significant. CONCLUSIONS: QIDS-SR16 cutoff ≥8 adds to the prognostic information available to practicing nephrologists during routine clinic visits from comorbidities and laboratory data. This cutoff score performs similar to a clinician diagnosis of MDD and provides a feasible and time-saving alternative to an interview-based MDD diagnosis for determining prognosis in CKD patients.

Relationship between obesity and depression: characteristics and treatment outcomes with antidepressant medication.

OBJECTIVE: Obesity and major depressive disorder often co-occur. However, differences between obese and normal-weight depressed patients and the moderating effect of obesity on antidepressant treatment outcome are not well studied. METHODS: Adults (n = 662) with major depressive disorder in the Combining Medications to Enhance Depression Outcomes study were randomized to treatment with escitalopram plus placebo, bupropion plus escitalopram, or venlafaxine plus mirtazapine for a 12-week primary treatment phase and 16-week follow-up. Body mass index (BMI) was calculated at baseline and categorized according to World Health Organization criteria: normal or low weight (NW), overweight, Obese I and Obese II+. A repeated-effects model, unadjusted and adjusted for baseline variables, assessed outcomes. RESULTS: Obesity was common (46.2%), only 25.5% were NW. Higher BMI was associated with greater medical illness (p < .001), social phobia (p = .003), and bulimia (p = .026). Lower BMI was associated with more frequent post-traumatic stress disorder (p = .002) and drug abuse (p < .001). Treatment outcomes did not differ including Week 12 remission rates (NW 36%, overweight 40%, Obese I 43%, Obese II+ 37%; p = .69). Lower BMI was associated with more frequent (p = .024 [unadjusted] and .053 [adjusted]) and more severe (p = .008 [unadjusted] and .053 [adjusted]) adverse effects. CONCLUSIONS: BMI was related to clinical presentation and prevalence of comorbidities, but not antidepressant outcomes. Lower BMI classes had more psychiatric comorbidities, potentially obscuring the relationship between BMI and antidepressant effects. Trial Registration ClinicalTrials.gov identifier: NCT00590863.

Health impacts of caregiving for older adults with functional limitations: results from the Singapore survey on informal caregiving.

OBJECTIVE: To estimate the health impact, in terms of depression, self-rated health, and health services utilization, of providing care to older adults (75+) requiring human assistance in at least one activity of daily living (ADL) limitation. METHOD: Data from 1,077 caregivers and 318 noncaregivers, interviewed in the Singapore Survey on Informal Caregiving, was used to examine differences in depressive symptoms, self-rated health, and number of outpatient visits in the last 1 month between caregivers and noncaregivers. Multivariate models for the outcomes, adjusting for characteristics of the caregiver/noncaregiver and care-recipient/potential care recipient, were run. RESULTS: Caregivers were more depressed, had poorer self-rated health, and had a higher rate of outpatient visits in the past month compared to noncaregivers. DISCUSSION: The study indicates the need for support services to family caregivers of older adults with ADL limitations.

Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication.

Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR16) by treatment exit, and remission as a final QIDS-SR16 of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR16 and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patient's residual depressive symptoms.

CYP2C19 variation and citalopram response.

OBJECTIVE: Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n= 1074). RESULTS: Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P = 0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P = 0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P = 0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram.