Apremilast for the Treatment of Mild-to-Moderate Hidradenitis Suppurativa in a Prospective, Open-Label, Phase 2 Study

Background: Treatment options are limited for patients with hidradenitis suppurativa (HS). Apremilast, an oral phosphodiesterase 4 inhibitor, may offer an attractive therapeutic option for patients with mild-to-moderate HS. Methods: This open-label, phase 2 clinical trial enrolled adults (≥18 years of age) with mild-to-moderate HS. Patients received apremilast 30mg twice daily for 24 weeks after a 5-day titration period. Therapy was discontinued at week 24; data were collected up to week 28. Hidradenitis Suppurativa Clinical Response 30 (HiSCR30), ie, proportion of patients with a ≥30% reduction in abscesses and nodules at week 16, was the primary endpoint. HiSCR50, ie, ≥50% reduction, was also explored. Mean changes from baseline to week 24 in the modified Sartorius, Physician's Global Assessment, visual analog scale (VAS) for pain, and Dermatology Life Quality Index (DLQI) scores were analyzed using the Wilcoxon Rank-Sum test. Adverse events (AEs) were summarized. Results: Twenty patients (mean age, 32.5 years) were enrolled in the study. HiSCR30 was achieved in 65% of patients at weeks 16 and 24. A similar proportion of patients achieved HiSCR50. Significant mean improvements from baseline were observed for all assessments. At week 24, the overall Sartorius score improved from 35.6 to 13.9 (-21.7 change; P<0.001), the PGA score from 2.7 to 1.6 (-1.1 change; P<0.01), the VAS pain score from 27.6 to 10.9 (-16.8 change; P<0.05), and the DLQI score from 11.6 to 5.4 (-6.2 change; P<0.01). Diarrhea (20%), nausea (15%), and depression (10%) were the most commonly reported AEs. No serious AEs or deaths were reported. Conclusions: Apremilast was safe and effective in improving HS disease activity, pain, and QoL in patients with mild-to-moderate HS. These data suggest that apremilast may have a role in the early treatment of less severe HS. J Drugs Dermatol. 2019;18(2):170-176.

The Importance of Early Treatment in Psoriasis and Management of Disease Progression.

Psoriasis is a chronic, immune-mediated, inflammatory disease that if left untreated can result in prolonged subclinical inflammation that affects a variety of organs, including the heart, liver, kidney, and intestines, as well as joints and muscles. Relatedly, psoriasis significantly increases patients' risks for developing certain comorbidities. Disease progression in psoriasis is unpredictable, and some patients have mild disease that is stable for many years, while in others, mild disease quickly progresses to moderate-to-severe psoriasis. Adding to the complexity of this disease, subclinical systemic inflammation is present in patients with either mild or moderate-to-severe psoriasis. In this review, key factors in psoriasis progression, including the role that systemic inflammation has in psoriasis pathogenesis and the development of comorbidities, are highlighted along with the ability of various therapies to potentially stop or slow the progression of psoriasis and its associated comorbidities. Additionally, practical guidance is provided for physicians regarding treatment and monitoring of disease progression based on psoriasis severity and the risk of comorbidities. J Drugs Dermatol. 2018;17(7):737-742.

The Temporal Associations of Therapeutic Alliance and Manual Adherence With Depressive Symptom Change in Cognitive Behavioral Therapy for Adult Outpatient Major Depression.

Background: The therapeutic alliance is considered an important causal agent of psychotherapy efficacy. However, studies in cognitive behavioral therapy (CBT) for depression have suggested that alliance might be more of a consequence rather than a cause of depressive symptom change, while adherence to CBT specific techniques was found to be associated with subsequent depression change. We aimed to add to this body of literature by assessing the temporal associations of both therapeutic alliance and manual adherence with depressive symptom change in a relatively large sample of depressed adult outpatients over the full course of CBT. Methods: Adults with a major depressive episode (n = 98) participating in a randomized clinical trial were offered 22 weeks of CBT and rated the Penn Helping Alliance Questionnaire (HAq-I) at weeks 5 and 22. Therapists rated their adherence to the CBT manual after each session and observers assessed the Hamilton Depression Rating Scale scores at weeks 0, 5, 10, and 22. Linear mixed model analyses were used to assess the associations of alliance and adherence with prior and subsequent depression change. Results: HAq-I Relationship and manual adherence ratings were not significantly associated with prior nor with subsequent depression change (p > 0.14). Prior depression change was associated with the HAq-I subscale Perceived helpfulness at the end of treatment (r = 0.30, CI = 0.03-0.56, p = 0.03). Conclusion: We were not able to replicate prior depression change in CBT for depression to be associated with improved quality of the therapeutic alliance when using a more "pure" measure of the therapeutic relationship. Limitations of this study include the subjective alliance and adherence assessments. Our findings indicate the need to appropriately distinguish between the perceived helpfulness and the relationship factors when examining therapeutic alliance.

Early interventions in cognitive behavioral therapy for depression: A study contrasting a low-adherent and a highly adherent case.

In cognitive behavioral therapy for depression, the first sessions play a crucial role in determining treatment outcome. In the first sessions, the therapist needs to form an alliance to facilitate application of the techniques; agree with the patient on problem definition, problem solution, and goals; explain the rationale; and create confidence in therapy by producing early symptom relief. This article illustrates the cognitive behavioral therapy treatment process of two depressed clients: one for whom the treatment manual was followed neatly and one for whom the therapist chose not to adhere to the manual strictly. Both had a comparable end result in terms of symptom change and alliance scores. The existing literature shows evidence for starting off with behavioral techniques, supported by assigning and reviewing homework, structuring sessions, and negotiating goals. The cases also illustrate that there are circumstances, such as urgent financial problems, in which the therapists may need to leave the treatment manual early in the therapy process, albeit temporarily. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cognitive Behavioral Therapy versus Short Psychodynamic Supportive Psychotherapy in the outpatient treatment of depression: a randomized controlled trial.

BACKGROUND: Previous research has shown that Short Psychodynamic Supportive Psychotherapy (SPSP) is an effective alternative to pharmacotherapy and combined treatment (SPSP and pharmacotherapy) in the treatment of depressed outpatients. The question remains, however, how Short Psychodynamic Supportive Psychotherapy compares with other established psychotherapy methods. The present study compares Short Psychodynamic Supportive Psychotherapy to the evidence-based Cognitive Behavioral Therapy in terms of acceptability, feasibility, and efficacy in the outpatient treatment of depression. Moreover, this study aims to identify clinical predictors that can distinguish patients who may benefit from either of these treatments in particular. This article outlines the study protocol. The results of the study, which is being currently carried out, will be presented as soon as they are available. METHODS/DESIGN: Adult outpatients with a main diagnosis of major depressive disorder or depressive disorder not otherwise specified according to DSM-IV criteria and mild to severe depressive symptoms (Hamilton Depression Rating Scale score > or = 14) are randomly allocated to Short Psychodynamic Supportive Psychotherapy or Cognitive Behavioral Therapy. Both treatments are individual psychotherapies consisting of 16 sessions within 22 weeks. Assessments take place at baseline (week 0), during the treatment period (week 5 and 10) and at treatment termination (week 22). In addition, a follow-up assessment takes place one year after treatment start (week 52). Primary outcome measures are the number of patients refusing treatment (acceptability); the number of patients terminating treatment prematurely (feasibility); and the severity of depressive symptoms (efficacy) according to an independent rater, the clinician and the patient. Secondary outcome measures include general psychopathology, general psychotherapy outcome, pain, health-related quality of life, and cost-effectiveness. Clinical predictors of treatment outcome include demographic variables, psychiatric symptoms, cognitive and psychological patient characteristics and the quality of the therapeutic relationship. DISCUSSION: This study evaluates Short Psychodynamic Supportive Psychotherapy as a treatment for depressed outpatients by comparing it to the established evidence-based treatment Cognitive Behavioral Therapy. Specific strengths of this study include its strong external validity and the clinical relevance of its research aims. Limitations of the study are discussed. TRIAL REGISTRATION: Current Controlled Trails ISRCTN31263312.

Cognitive-behavioral versus psychodynamic therapy for major depression: Secondary outcomes of a randomized clinical trial.

OBJECTIVE: In a randomized clinical trial, we compared the efficacy of cognitive-behavioral therapy (CBT) and psychodynamic therapy for adult outpatient depression on measures of psychopathology, interpersonal functioning, pain, and quality of life. METHOD: There were 341 Dutch adults (70.1% female, mean age = 38.9, SD = 10.3) meeting Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV) criteria for a major depressive episode and with a Hamilton Depression Rating Scale (HAM-D) score ≥14, who were randomized to 16 sessions of individual manualized CBT or short-term psychodynamic supportive psychotherapy. Severely depressed patients (HAM-D >24) received additional antidepressant medication according to a protocol. Outcome measures included the Brief Symptom Inventory, Beck Anxiety Inventory, Outcome Questionnaire, a visual analogue scale for pain, and EuroQol. Data were analyzed with mixed model analyses using intention-to-treat samples. Noninferiority margins were prespecified as Cohen's d = -0.30. RESULTS: Across treatment conditions, 45-60% of the patients who completed posttreatment assessment showed clinically meaningful change for most outcome measures. We found no significant differences between the treatment conditions on any of the outcome measures at both posttreatment and follow-up. Noninferiority of psychodynamic therapy to CBT was shown for posttreatment and follow-up anxiety measures as well as for posttreatment pain and quality of life measures, but could not be consistently demonstrated for the other outcomes. CONCLUSIONS: This is the first study that shows that psychodynamic therapy can be at least as efficacious as CBT for depression on important aspects of patient functioning other than depressive symptom reduction. These findings extend the evidence-base of psychodynamic therapy for depression, but replication is needed by means of rigorously designed noninferiority trials. (PsycINFO Database Record

Therapist-rated outcomes in a randomized clinical trial comparing cognitive behavioral therapy and psychodynamic therapy for major depression.

BACKGROUND: The efficacy of psychodynamic therapy (PDT) for depression is debated due to a paucity of high-quality studies. We compared short psychodynamic supportive psychotherapy (SPSP) to cognitive behavioral therapy (CBT) in a randomized clinical trial. We used therapist-rated outcomes to examine how the course of change during treatment could be best represented and to compare treatment efficacy, hypothesizing non-significant differences. METHODS: Three hundred and forty-one adults meeting DSM-IV criteria for a depressive episode and with Hamilton Depression Rating Scale (HAM-D) scores ≥14 were randomized to 16 sessions of individual manualized CBT or SPSP. Severely depressed patients (HAM-D>24) received additional antidepressant medication. After each session, therapists rated the Clinical Global Impression Scale subscales 'Severity of Illness' (CGI-S) and 'Global Improvement' (CGI-I), and the DSM-IV Axis V Global Assessment of Functioning Scale (GAF). We fitted growth curves using mixed model analyses with intention-to-treat samples. RESULTS: CGI-S and GAF scores during treatment were best represented by a linear symptom decrease. CGI-I scores were best represented by an S-shaped curve with relative more improvement in the first and last phases than in the middle phase of treatment. No significant post-treatment treatment differences were found. A non-significant trend for a treatment effect on CGI-S scores vanished when controlling for therapist gender and profession. LIMITATIONS: Therapists were not specifically trained for CGI and GAF assessments. CONCLUSIONS: These findings add to the evidence-base of PDT for depression. Therapist characteristics and differences between severity and improvement measures might influence ratings and need to be taken into account when using therapist-rated outcome measures.

The efficacy of cognitive-behavioral therapy and psychodynamic therapy in the outpatient treatment of major depression: a randomized clinical trial.

OBJECTIVE: The efficacy of psychodynamic therapies for depression remains open to debate because of a paucity of high-quality studies. The authors compared the efficacy of psychodynamic therapy with that of cognitive-behavioral therapy (CBT), hypothesizing nonsignificant differences and the noninferiority of psychodynamic therapy relative to CBT. METHOD: A total of 341 adults who met DSM-IV criteria for a major depressive episode and had Hamilton Depression Rating Scale (HAM-D) scores ≥14 were randomly assigned to 16 sessions of individual manualized CBT or short-term psychodynamic supportive therapy. Severely depressed patients (HAM-D score >24) also received antidepressant medication according to protocol. The primary outcome measure was posttreatment remission rate (HAM-D score ≤7). Secondary outcome measures included mean posttreatment HAM-D score and patient-rated depression score and 1-year follow-up outcomes. Data were analyzed with generalized estimating equations and mixed-model analyses using intent-to-treat samples. Noninferiority margins were prespecified as an odds ratio of 0.49 for remission rates and a Cohen's d value of 0.30 for continuous outcome measures. RESULTS: No statistically significant treatment differences were found for any of the outcome measures. The average posttreatment remission rate was 22.7%. Noninferiority was shown for posttreatment HAM-D and patient-rated depression scores but could not be demonstrated for posttreatment remission rates or any of the follow-up measures. CONCLUSIONS: The findings extend the evidence base of psychodynamic therapy for depression but also indicate that time-limited treatment is insufficient for a substantial number of patients encountered in psychiatric outpatient clinics.