Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate-to-severe plaque psoriasis and non-pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2 and UNCOVER-3).

BACKGROUND: Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. OBJECTIVE: To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis and moderate-to-severe non-pustular palmoplantar involvement. METHODS: In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis [UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224), UNCOVER-3 (N = 1346)] were randomized to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160-mg starting dose, or placebo through week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg etanercept biweekly. Patients entering the open-label long-term extension (UNCOVER-3) received ixekizumab Q4W weeks 12-60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index (PPASI) ≥8. RESULTS: Twenty-eight percent of UNCOVER-1, UNCOVER-2 and UNCOVER-3 patients had baseline palmoplantar involvement (PPASI ≥0, n = 1092) and 9.1% (n = 350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician's Global Assessment ≥4. Higher percentages of patients treated with ixekizumab vs. placebo or etanercept achieved PPASI 50 (approximately 80% vs. 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% vs. 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P < 0.05). PPASI 100 was achieved by higher percentages of ixekizumab-treated patients vs. placebo (approximately 50% vs. 8.2%, P < 0.001) and ixekizumab Q2W-treated patients vs. etanercept (51.8% vs. 32.2%, P < 0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1. CONCLUSION: In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment.

Treatment and outcomes for patients with depression who are partial responders to SSRI treatment: post-hoc analysis findings from the FINDER European observational study.

BACKGROUND: Remission is the goal in depression, but in practice many patients only experience a partial response to treatment. We sought to determine the prevalence, management and subsequent outcomes of partial responder patients. METHODS: Patients enrolled in the naturalistic Factors Influencing Depression Endpoints Research (FINDER) study with the Hospital Anxiety and Depression Scale depression subscale (HADS-D) score >10 at baseline who received only SSRI(s) between 0 and 3 months comprised the study cohort (n=1147). Patients were categorized as remitters, partial responders or non-responders at 3 months and then followed up at 6 months. RESULTS: At 3 months, 29.4% of the study population were considered non-responders, 27.6% were partial responders, and 39.3% were remitters. Most partial responders at 3 months remained on the same SSRI for the next 3 months. Of the 247 partial responders at 3 months and remained on the same SSRI(s) between 3 and 6 months, 10.9% met criteria for non-response at 6 months, 32.4% remained partial responders, and 56.3% achieved remission. Quality of life outcomes for the partial responders were significantly worse than those in remission (p<0.05). LIMITATIONS: FINDER was an observational study; the current analysis was conducted post-hoc. Multivariable methods were not applied and findings are primarily descriptive and exploratory. CONCLUSIONS: Partial response is common and patients in partial response have a poorer quality of life than those achieving remission. Despite this, the majority of partial responders continue to take the same SSRI. Our findings underscore the importance of continuing to strive for remission.

Impact of fatigue on outcome of selective serotonin reuptake inhibitor treatment: secondary analysis of STAR*D.

OBJECTIVE: To explore relationships between baseline and changes in fatigue during treatment with outcomes in patients with major depressive disorder (MDD) receiving citalopram monotherapy. RESEARCH DESIGN AND METHODS: Secondary analyses of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Level 1 treatment phase (≤14 weeks citalopram monotherapy). Fatigue was assessed with item 14 on energy level from the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16; scored 0-3: 0 = no fatigue, 3 = maximal fatigue); prospective fatigue: assessment of fatigue at Level 1 entry and exit (no fatigue, treatment-emergent fatigue, remitted fatigue, or residual fatigue). CLINICAL TRIAL REGISTRATION: Http://clinicaltrials.gov, NCT00021528. MAIN OUTCOME MEASURES: Remission of depressive symptoms (17-item Hamilton Rating Scale for Depression ≤7 or QIDS-SR16 ≤5); Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form; Short-Form Health Survey Mental and Physical subscales; and Work and Social Adjustment Scale (WSAS). RESULTS: At baseline, of 2868 patients included in the analyses, 5.5% had a QIDS-SR16 item 14 score of 0; 22.9%, a score of 1; 53.6%, a score of 2; and 18.0%, a score of 3. During Level 1 treatment, 3.5% of patients had no prospective fatigue, 2.1% had treatment-emergent fatigue, 33.6% had fatigue remitting during treatment, and 60.8% had residual fatigue. Female gender, unemployment, fewer years of education, and lower monthly income were significantly associated with higher rates of baseline fatigue (all P < 0.0001). Higher levels of baseline or prospective fatigue were associated with reduced likelihood of remission, decreased overall satisfaction (P < 0.0001), and reduced mental and physical function at outcome (P ≤ 0.05). Patients with higher baseline or prospective fatigue reported higher WSAS total scores (P < 0.0001), indicative of more severe functional impairment. CONCLUSIONS: Lower baseline fatigue and remission of fatigue during antidepressant treatment in patients with MDD are associated with higher rates of remission of depressive symptoms and better function and quality of life. Study limitations include use of the STAR*D Level 1 sample (citalopram as only antidepressant), use of a proxy measure of energy/fatigue (item 14 from the QIDS-SR16), and the secondary post-hoc analysis design.

Use of quetiapine in bipolar disorder: a case series with prospective evaluation.

Quetiapine, a new atypical antipsychotic, was added to ongoing treatment of bipolar I outpatients (n=15) for symptoms of illness (mood lability, irritability, psychosis and/or difficulty sleeping). All evaluations were prospectively obtained, with the majority of patients (n=9) showing much or very much improvement on the Clinical Global Impression for Bipolar Disorder (CGI-BP). Somatic complaints were limited. Mean (SD) duration before changes in medication regimens was 134 (100) days. Studies of the use of quetiapine in maintenance treatment of bipolar disorder are warranted.

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.

Texas Medication Algorithm Project: development and feasibility testing of a treatment algorithm for patients with bipolar disorder.

BACKGROUND: Use of treatment guidelines for treatment of major psychiatric illnesses has increased in recent years. The Texas Medication Algorithm Project (TMAP) was developed to study the feasibility and process of developing and implementing guidelines for bipolar disorder, major depressive disorder, and schizophrenia in the public mental health system of Texas. This article describes the consensus process used to develop the first set of TMAP algorithms for the Bipolar Disorder Module (Phase 1) and the trial testing the feasibility of their implementation in inpatient and outpatient psychiatric settings across Texas (Phase 2). METHOD: The feasibility trial answered core questions regarding implementation of treatment guidelines for bipolar disorder. A total of 69 patients were treated with the original algorithms for bipolar disorder developed in Phase 1 of TMAP. RESULTS: Results support that physicians accepted the guidelines, followed recommendations to see patients at certain intervals, and utilized sequenced treatment steps differentially over the course of treatment. While improvements in clinical symptoms (24-item Brief Psychiatric Rating Scale) were observed over the course of enrollment in the trial, these conclusions are limited by the fact that physician volunteers were utilized for both treatment and ratings. and there was no control group. CONCLUSION: Results from Phases 1 and 2 indicate that it is possible to develop and implement a treatment guideline for patients with a history of mania in public mental health clinics in Texas. TMAP Phase 3, a recently completed larger and controlled trial assessing the clinical and economic impact of treatment guidelines and patient and family education in the public mental health system of Texas, improves upon this methodology.

Guidelines for treatment of bipolar disorder.

Medication guidelines are being incorporated into psychiatric care, and may serve multiple functions, including ensuring consistent quality care, minimizing or managing costs, integration of new treatments, and providing clinicians with information necessary to make informed clinical decisions. Methods of guideline development and the published guidelines for the medication treatment of bipolar disorder are briefly reviewed. Despite limited research on the clinical efficacy of using guidelines, they serve other useful functions such as prioritizing multiple treatment options and providing a framework for treatment. The future role of treatment algorithms in psychiatric practice will be determined, in part, by results of studies evaluating the clinical impact of their use.

The longitudinal course of bipolar disorder.

Course of illness is central to our focus on bipolar disorder due to the lifelong nature of this illness in the majority of patients. In this overview, we highlight areas of consensus and debate on factors that impact course of illness. Findings on age at onset, psychiatric comorbidity, frequency of episodes, cycle pattern, rapid cycling, mixed symptoms, and precipitants of episodes including use of substances and antidepressants and lithium discontinuation are discussed. The diversity and range of presentation and even course of illness become quickly apparent in this review. Highlighting these factors rather than seeking a unifying theory should be a productive way to refine our ability to identify additive factors contributing to course of illness for patients with bipolar disorder.

AIDS education intervention utilizing a person with AIDS: examination and clarification.

The utility of a person with AIDS (PWA) in conveying AIDS information to college students is assessed. Mode of transmission of HIV is proposed to serve as a moderating variable in students' receptivity to the AIDS information and perception of the source of AIDS information. Two-hundred-sixty undergraduate students received a standardized lecture by a confederate, posing as a PWA, who revealed HIV positive status through either heterosexual transmission, homosexual transmission, needle-sharing, or a blood transfusion. Control conditions received the lecture from a neutral presenter (no HIV status disclosure) or no contact. All the HIV conditions were superior to the Control condition in increasing knowledge about AIDS and AIDS prevention. Additionally, students rated the PWA more positively than the neutral presenter on a number of evaluative dimensions. Mode of transmission served a mediating effect, with the confederate viewed most favorably in the Heterosexual and Transfusion conditions, and less favorably in the i.v. Drug and Homosexual conditions. Implications for educational programs are discussed.