Stepwise Treatment Algorithm Research Articles

Optimizing diuretic management in acute decompensated heart failure: the impact of diuretic algorithm in real-world setting

Abstract Background/Introduction Achieving euvolaemia is an important prognostic factor in acutely decompensated heart failure (ADHF). The European Society of Cardiology (ESC) guidelines suggest that a stepwise diuretic treatment algorithm based on regular reassessment of urinary output and natriuresis may be superior compared to current standard of care. We studied the implementation and effectiveness of such a pre-specified algorithm in a real-word cohort for realizing euvolaemia. Methods In 2020 we implemented the stepped diuretic strategy from the Heart Failure Association position statement, now stated in the 2021 ESC guidelines, in a peripheral hospital. Afterwards we conducted a retrospective cohort study, including patients with ADHF (with hospitalization duration > 3 days for decongestive treatment). Patients admitted between 10-Jan-2021 and 04-Dec-2021, who were treated according to the diuretic algorithm (protocol cohort), were compared to patients who were treated between 04-Jan-2018 and 19-jan-2019 (before implementation of this algorithm). Our primary outcomes were length of hospital stay (days), complications during hospitalization, such as electrolyte disturbance, kidney function, arrhythmias, infections and mortality during hospitalization. Results The study comprised 221 patients, with 107 in the pre-protocol cohort and 114 in the protocol cohort. Baseline characteristics were similar between the cohorts, expect for the kidney function and NT-proBNP levels at admission. Mean eGFR was slightly better in the protocol cohort (53 [36-71] vs 43 [29-63] ml/min/1.73m2, p .016), were as NT-proBNP was higher in the pre-protocol cohort (990 vs 480 pmol/l) (Table 1). The mean length of stay was shorter in the protocol cohort (7.0 [5.1-10.3] vs 7.5 [5.9-10.9] days). The incidence of complications, such as electrolyte disturbances and arrhythmias, were comparable. Notably, the mean eGFR on third day of hospitalization was higher in the protocol cohort (50 ± 21 vs. 42 ± 19 ml/min/1.73m2). There was a difference in the median weight lost during the admission between the two cohorts (Figure 1). Conclusion Our data suggest that a pre-specified stepwise diuretic treatment algorithm, based on urinary output is feasible and effective in achieving euvolaemia in a real-world cohort. Furthermore, it reduces length of hospital stay without increasing the risk of complications.

2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines.

Canine and feline endocrinopathies reflect an endocrine gland disease or dysfunction with resulting hormonal abnormali ties that can variably affect the patient's wellbeing, quality of life, and life expectancy. These guidelines provide consensus recommendations for diagnosis and treatment of four canine and feline endocrinopathies commonly encountered in clini cal practice: canine hypothyroidism, canine hypercortisolism (Cushing's syndrome), canine hypoadrenocorticism (Addi son's disease), and feline hyperthyroidism. To aid the general practitioner in navigating these common diseases, a stepwise diagnosis and treatment algorithm and relevant background information is provided for managing each of these diseases. The guidelines also describe, in lesser detail, the diagnosis and treatment of three relatively less common endo crinopathies of cats: feline hyperaldosteronism, feline hypothyroidism, and feline hyperadrenocorticism. Additionally, the guidelines present tips on effective veterinary team utilization and client communication when discussing endocrine cases.

An Algorithm Recommendation for Management of Allergic Rhinitis in the United Arab Emirates: A Consensus Statement from an Expert Panel

Background: Allergic rhinitis (AR) is a common chronic health problem in the United Arab Emirates (UAE). Achieving adequate symptom control is pivotal to successful AR management, which may be attained following a stepwise treatment algorithm. Despite the availability of several guideline recommendations for the best management of AR, morbidity remains high in patients with AR, with treatment goals being far from the reach. Objective: The objective of this consensus statement was to discuss the currently available knowledge on the treatment of AR and to provide an expert opinion on the use of MP-AzeFlu (azelastine HCl, AZE; 137 µg per spray) and INCS (fluticasone propionate, FP; 50 µg per spray) for the effective management of AR in the UAE. Methods: A consensus meet involving 13 otorhinolaryngologists and one pulmonologist was held in Dubai, UAE, to discuss the current understanding on the treatment and management of AR. Results: The panel advised to start AR pharmacotherapy with antihistamines (AH), leukotriene receptor antagonist (LTRA), INCS or MP-AzeFlu based on the visual analogue scale (VAS) score. In mild intermittent AR (VAS score <5/10), AH or LTRA is recommended as first-line therapy. However, in case of VAS score ≥5/10 or persistent AR, and treatment failure with AHs alone, INCS or MP-AzeFlu is recommended followed by reassessment for 7 days to confirm a step-up or step-down down therapy. Patients non-responsive to therapy were advised to step-up with MP-AzeFlu. Conclusion: The panel advocated a combination of intranasal second-generation AH and INCS in a single device (Dymista®) as first-line therapy for the management of AR. The algorithm provided herein can be applied in most healthcare settings by following a step-up or step-down strategy based on the VAS scores for AR control in the UAE.

Taiwan guidelines for the diagnosis and management of pediatric atopic dermatitis: Consensus statement of the Taiwan Academy of Pediatric Allergy, Asthma and Immunology

Atopic dermatitis (also known as atopic eczema) is a chronic relapsing inflammatory skin disease commonly seen in children, with increasing prevalence over the past few decades in many countries including Taiwan. The management of pediatric atopic dermatitis can be challenging, particularly as treatment options are expanding with the emergence of novel systemic and topical anti-inflammatory medications in recent years. The Taiwan Academy of Pediatric Allergy, Asthma and Immunology (TAPAAI) has developed the Taiwan guidelines for the diagnosis and management of pediatric atopic dermatitis, which provides a concise overview of its epidemiology, clinical characteristics and diagnosis, mechanisms, treatments, and education. The contents of this guideline integrate the principles of recent national and international guidelines for the diagnosis and management of atopic dermatitis, latest research findings, and expert opinions of experienced pediatric allergy specialists in Taiwan. For practical purposes, this guideline presents simplified and easy-to-use diagnostic criteria and severity grading for pediatric atopic dermatitis. A stepwise treatment algorithm is also proposed to expedite rational, cost-effective, and evidence-based management strategy. This guideline, developed based on current best evidence and real-world experience of pediatric allergy experts in Taiwan, is intended to facilitate practical, up-to-date management of pediatric atopic dermatitis among physicians.

Treatment of paediatric Lisfranc injuries: A systematic review and introduction of a novel treatment algorithm.

Background:Pediatric Lisfranc injuries (PLI) are rare injuries that have few studies published about their occurrence and treatment in pediatric population. Due to this lack of information, the diagnostic criteria and surgical or non-surgical methods for treatment have not been clearly established within the pediatric orthopedic literature. The objective of this study was to review the published literature related to treatment options and develop a concise stepwise treatment algorithm for pediatric patients presenting with Lisfranc injuries.Methods:A systematic literature review was conducted using PubMed to find studies discussing the treatment of PLI with reported long-term outcomes. Data collection accounted for the mechanism of injury, diagnostic imaging modality used, injury type, fracture classification using the Myerson system, treatment method used, and postoperative complications.Results:An initial PubMed search revealed 290 articles, but only 10 studies fulfilled the criteria for in-depth review. A total of 114 patients were included in this review from the selected case reports and case series studies. Primary treatment methods were as follows: 44% (50/114) with open reduction internal fixation (ORIF) using Kirschner wires (K-wires) and/or screws, 3% (3/114) with closed reduction percutaneous fixation (CRPF), 4% (4/114) with suture-button constructs, 20% (23/114) with cast immobilization, and 29% (33/114) were described as not requiring reduction.Conclusion:There were two main limitations to this study. First, there are few published studies with longitudinal outcomes of PLI treatment. Second, some case series did not disclose which procedure a patient with post-treatment complications underwent. Therefore, an overall statistical analysis of success and failure rates with associated complications of each procedure could not be conducted. In conclusion, we found that a stepwise approach to evaluating conservative and surgical treatment options based on the presentation of the PLI should be utilized to optimize long-term outcomes.

Systemic Medical and Procedural Therapies for Mucosal Lichen Planus: Update and Review of Challenges and Successes

Context: Mucosal lichen planus is a chronic inflammatory debilitating condition that commonly affects the oral mucosa, but other sites such as the genital and ocular mucosae, esophagus and ear canal may also be involved, with risk of scarring and functional compromise. Spontaneous remission is rare and the condition tends to be recalcitrant to therapy, which makes management challenging. Topical therapies are often ineffective in severe cases and official treatment guidelines including systemic agents and procedural interventions are currently not available. Methods: We performed a literature review on current systemic therapies for mucosal lichen planus using PubMed, MEDLINE and Cochrane databases, with 74 publications identified including retrospective and prospective studies, case reports, and clinical trials. Therapies reviewed included biologics, immunosuppressive therapies, immunomodulating and anti-inflammatory drugs, vitamin A derivatives, devices and interventional therapies, and non-prescription drugs. Results: Reported treatments were classified into the following categories: biologics, anti-metabolic immunosuppressives, direct anti-T cell agents, other immunodulatory agents, antibiotics, retinoids, and procedure based interventions. Most studies on mucosal lichen planus are descriptive in nature and demonstrate low levels of evidence. Randomized controlled trials are lacking, which makes it difficult to directly compare different grading scales and outcome. Conclusions: The authors suggest clinical criteria for initiation of therapy in mucosal lichen planus, such as severe disease, lack of response to topical therapy, mucous membranes involvement and involvement of organs at risk of non-function. The authors also propose a stepwise treatment algorithm based on data from this review and their personal experience in an academic tertiary referral center.

Opioid-induced constipation: a stepwise treatment algorithm feasibility study

BackgroundOpioid-induced constipation (OIC) is frequently undertreated in patients with advanced cancer. Our hypothesis is that the use of a stepwise treatment algorithm, supported by regular patient-reported outcome measures, should improve...

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

ICS-formoterol reliever versus ICS and short-acting β2-agonist reliever in asthma: a systematic review and meta-analysis.

BackgroundThe Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting β2-agonist (SABA) reliever at step 2 of its stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on prevention of severe exacerbation.MethodsWe performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (identifier number CRD42020154680).ResultsFour RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95% CI 0.73–1.00; p=0.048) and reduced daily ICS dose (mean difference −177.3 μg, 95% CI −182.2–−172.4 μg). Asthma symptom control was worse in the as-needed group (Asthma Control Questionnaire-5 mean difference 0.12, 95% CI 0.09–0.14), although this did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (OR 1.07, 95% CI 0.84–1.36).ConclusionAs-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.

A Focused Update on Tardive Dyskinesia.

Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication following chronic exposure to centrally acting dopamine receptor antagonists, mainly of the class of antipsychotics drugs. New generations of antipsychotic drugs reduced its mean prevalence to 20%, but it continues to mar the drug experience and social integration in a significant fraction of patients. The underlying molecular cascade remains elusive, explaining in part why TD management is so often difficult. Protocol variations between experimental laboratories and inter-species differences in the biological response to antipsychotic drugs have added layers of complexity. The traditional dopamine D2 receptor supersensitivity hypothesis was revisited in an experimental nonhuman primate model. Findings in the striatum revealed a strong upregulation of D3, not D2, receptors specific to dyskinetic animals, and indirect evidence suggestive of a link between overactivation of glycogen synthase kinase-3β signaling and TD. New effective vesicular monoamine transporter type 2 inhibitors alleviating TD have been approved in the USA. They were integrated to an emerging stepwise treatment algorithm for troublesome TD, which also includes consideration for changes in the current antipsychotic drug regimen and recognition of potentially aggravating factors such as anticholinergic co-medications. These advances may benefit TD.

ICS-formoterol reliever therapy stepwise treatment algorithm for adult asthma

A practical “anti-inflammatory reliever therapy”-based algorithm based on the GINA 2019 update is presented, together with a prototype action plan to facilitate its implementation.http://bit.ly/33C2s5u

Diagnostic features, treatment, and outcome of dogs with inflammatory protein-losing enteropathy.

BackgroundProtein‐losing enteropathy (PLE) because of chronic inflammatory enteropathy (CIE) in dogs is often treated with a combination of glucocorticoids and second‐line immunosuppressant (SLI). This combined approach might not be necessary in all dogs.Hypothesis/objectivesTo describe diagnostic features and outcomes of dogs with PLE treated with glucocorticoids alone (group P) or with glucocorticoids and SLI (group S).AnimalsThirty‐one dogs with PLE.Material and methodsRetrospective analysis of signalment data from diagnostic procedures, treatment, and outcome of dogs with CIE/PLE (from 2015 to 2017), using the hospital's digital case database. Dogs with hypoalbuminemia and CIE were included. Because of a stepwise treatment algorithm, dogs were allocated to group P or S. Time to serum albumin concentrations ≥20 g/L and survival data were collected. Dogs were additionally categorized by their albumin and cobalamin serum concentrations. Multivariate and univariate analysis as well as Pearson's correlation and Kaplan‐Maier survival analysis were performed.ResultsSeventeen dogs were included in group P and 14 in group S. World Small Animal Veterinary Association score of the duodenum was different between groups (P = .05), but none of the other examined data. Median time until serum albumin reached >20 g/L was 13 days. Median survival time after start of treatment was 85 days (range, 13‐463 days) in group P and 166 days (range, 8‐390 days) in group S.Conclusion and Clinical ImportanceNo routine diagnostic test was predictive of clinical response, treatment group, or outcome. Glucocorticoid treatment alone can be appropriate in dogs with PLE.

Management Algorithm for Fungal Keratitis: The TST (Topical, Systemic, and Targeted Therapy) Protocol.

To evaluate the efficacy of the topical, systemic and targeted therapy (TST) protocol in management of fungal keratitis. All cases of treatment-naive smear- or culture-proven fungal keratitis presenting between June 2013 and May 2017 were recruited. The TST protocol included initial treatment with topical natamycin 5% with addition of oral ketoconazole or voriconazole in ulcers with size >5 mm, depth >50%, or impending perforation. Topical voriconazole 1% was included in case of poor response at 7 to 10 days. Intrastromal or intracameral antifungal injections were administered in case of poor response to combination therapy. Penetrating keratoplasty was performed in case of poor response to any of the regimen. The study included 223 cases of fungal keratitis with a mean age of 43.6 ± 15.3 years and a male-to-female ratio of 1.8:1. The mean area of the ulcer and infiltrate at presentation was 25.52 ± 19 and 25.7 ± 14.4 mm, respectively. Corrected distance visual acuity at presentation was 2.05 ± 0.43 logMAR that improved to 1.6 ± 0.4 logMAR at 3 months. Fusarium (42.2%) was the most common microorganism isolated, followed by Aspergillus (32.8%). The mean healing time was 41.5 ± 22.2 days, with a final scar size of 14.6 ± 8.2 mm. The treatment success rate with the TST protocol was 79.8%. Corneal perforation developed in 7% of cases (n = 15), and keratoplasty was performed for 20.2% of cases (n = 45). The TST protocol provides a stepwise treatment algorithm for management of cases of fungal keratitis with varying severity.

A standardized stepwise drug treatment algorithm for depression reduces direct treatment costs in depressed inpatients ‐ Results from the German Algorithm Project (GAP3)

BackgroundIn a previous single center study we found that a standardized drug treatment algorithm (ALGO) was more cost effective than treatment as usual (TAU) for inpatients with major depression. This report aimed to determine whether this promising initial finding could be replicated in a multicenter study. MethodsTreatment costs were calculated for two time periods: the study period (from enrolment to exit from study) and time in hospital (from enrolment to hospital discharge) based on daily hospital charges. Cost per remitted patient during the study period was considered as primary outcome. Results266 patients received ALGO and 84 received TAU. For the study period, ALGO costs were significantly lower than TAU (ALGO: 7 848 ± 6 065 €; TAU: 10 033 ± 7 696 €; p = 0.04). For time in hospital, costs were not different (ALGO: 14 734 ± 8 329 €; TAU: 14 244 ± 8 419 €; p = 0.617). Remission rates did not differ for the study period (ALGO: 57.9%, TAU: 50.0%; p=0.201). Remission rates were greater in ALGO (83.3%) than TAU (66.2%) for time in hospital (p = 0.002). Cost per remission was lower in ALGO (13 554 ± 10 476 €) than TAU (20 066 ± 15 391 €) for the study period (p < 0.001) and for time in hospital (ALGO: 17 582 ± 9 939 €; TAU: 21 516 ± 12 718 €; p = 0.036). LimitationsIndirect costs were not assessed. Different dropout rates in TAU and ALGO complicated interpretation. ConclusionsTreatment algorithms enhance the cost effectiveness of the care of depressed inpatients, which replicates our prior results in an independent sample.

Advances in Chronic Urticaria

In recent years, there have been important advances in our knowledge and management of chronic urticaria, a frequently debilitating disease. This review will be an update on the significant progress made in diagnostic and therapeutic procedures, as well as the classification, pathophysiology and assessment tools available for urticaria. Some of the latest advances will be detailed, including new findings that shed light on the mechanism of chronic urticaria. Updated information on optimal management of chronic urticaria will be discussed, including evidence on newer therapy, primarily the humanized monoclonal anti-IgE antibody, omalizumab. This is now considered to be third-line therapy after licensed doses of antihistamines and unlicensed updosing of antihistamines fourfold. Further understanding of the pathogenesis of chronic urticaria may help explain the mechanisms involved in the action of treatments. This would then aid the clinician with the appropriate diagnostic tests and therapeutic options. Extensive research on the administration of omalizumab has determined optimal dosage, the interval and duration of treatment. Recent studies have significantly advanced the treatment of chronic urticaria refractory to antihistamines, and the stepwise treatment algorithm has been updated in accordance with new evidence. Biomarkers, such as the basophil histamine release assay and autologous skin serum test, have been useful to identify chronic autoimmune urticaria, a subset of chronic urticaria, and may aid selection of third-line therapy, as well as predict speed of response and prognosis.

Outcomes After Conservative, Endoscopic, and Surgical Treatment of Groove Pancreatitis

Groove pancreatitis (GP) is a focal form of chronic pancreatitis affecting the paraduodenal groove area, for which consensus on diagnosis and management is lacking. We performed a systematic review of the literature to determine patient characteristics and imaging features of GP and to evaluate clinical outcomes after treatment. Eight studies were included reporting on 335 GP patients with a median age of 47 years (range, 34 to 64 y), with 90% male, 87% smokers, and 87% alcohol consumption, and 47 months (range, 15 to 122 mo) of follow-up. Most patients presented with abdominal pain (91%) and/or weight loss (78%). Imaging frequently showed cystic lesions (91%) and duodenal stenosis (60%).Final treatment was conservative (eg, pain medication) in 29% of patients. Endoscopic treatment (eg, pseudocyst drainage) was applied in 19% of patients-34% of these patients were subsequently referred for surgery. Overall, 59% of patients were treated surgically (eg, pancreatoduodenectomy). Complete symptom relief was observed in 50% of patients who were treated conservatively, 57% who underwent endoscopic treatment, and 79% who underwent surgery. GP is associated with male gender, smoking, and alcohol consumption. The vast majority of patients presents with abdominal pain and with cystic lesions on imaging. Although surgical treatment seems to be the most effective, both conservative and endoscopic treatment are successful in about half of patients. A stepwise treatment algorithm starting with the least invasive treatment options seems advisable.

PARADIGM - HF: The Rise of the Arnis.

Heart failure remains a widespread commonly encountered clinical condition. It is responsible for increased healthcare expenditure, driven by frequent and often prolonged hospital admissions associated with an increased mortality. A clinically useful classification of the syndrome is, patients with left ventricular systolic impairment (Heart Failure and reduced ejection fraction, HFREF) and patients with preserved left ventricular systolic function (HFPEF). The pharmacological treatment for patients with HFREF has evolved over the last twenty five years, focusing on modulation of the neurohormonal activation which represents a hallmark of this condition. This has led to the development of a stepwise treatment algorithm predominately based on inhibition of the renin angiotensin aldosterone pathway and counteracting sympathetic over-activation. In particular since the early trials in chronic heart failure (CHF) demonstrated a significant mortality benefit with ACE-inhibitors, subsequent studies have been conducted in conjunction with these drugs. The rationale being that it would be unethical to trial any new agent without the concomitant use of ACE-inhibitors. The recent publication of the PARADIGM -HF study has challenged this convention by trialling a novel pharmacological agent against an ACE-inhibitor in a landmark trial. The review sets out the current pharmacological treatment for patients with heart failure and discusses the recent findings with this novel class of medication.

A stepwise approach in the management of chronic spontaneous urticaria in children.

BackgroundThere is limited literature in the management of chronic urticaria in children. Treatment algorithms are generally extrapolated from adult studies.ObjectiveUtility of a weight and age-based algorithm for antihistamines in management of chronic spontaneous urticaria (CSU) in childhood. To document associated factors that predict for step of control of CSU and time taken to attain control of symptoms in children.MethodsA workgroup comprising of allergists, nurses, and pharmacists convened to develop a stepwise treatment algorithm in management of children with CSU. Sequential patients presenting to the paediatric allergy service with CSU were included in this observational, prospective study.ResultsNinety-eight patients were recruited from September 2012 to September 2013. Majority were male, Chinese with median age 4 years 7 months. A third of patients with CSU had a family history of acute urticaria. Ten point two percent had previously resolved CSU, 25.5% had associated angioedema, and 53.1% had a history of atopy. A total of 96.9% of patients achieved control of symptoms, of which 91.8% achieved control with cetirizine. Fifty percent of all the patients were controlled on step 2 or higher. Forty-seven point eight percent of those on step 2 or higher were between 2 to 6 years of age compared to 32.6% and 19.6% who were 6 years and older and lesser than 2 years of age respectively. Eighty percent of those with previously resolved CSU required an increase to step 2 and above to achieve chronic urticaria control.ConclusionWe propose a weight- and age-based titration algorithm for different antihistamines for CSU in children using a stepwise approach to achieve control. This algorithm may improve the management and safety profile for paediatric CSU patients and allow for review in a more systematic manner for physicians dealing with CSU in children.

Intraurethral Steroids are a Safe and Effective Treatment for Stricture Disease in Patients with Biopsy Proven Lichen Sclerosus

We investigated outcomes of the contemporary practice of administering intraurethral steroids to treat stricture disease in patients with biopsy proven lichen sclerosus. We performed an institutional review board approved review of the records of patients with biopsy proven lichen sclerosus stricture disease from October 2010 to September 2015. Study inclusion criteria were age 18 years or greater and male gender. Extracted data included patient demographics, comorbidities, location of lichen sclerosus, previous therapies and need for further interventions. Management was considered successful when there was no need for subsequent escalation of therapy. The intraurethral steroid regimen consisted of applying clobetasol cream to the affected urethra to lubricate a calibration device such as a urinary catheter or meatal dilator. The initial phase of therapy included twice daily application for 2 to 3 months, at which point the frequency was decreased by the clinician, enabling the patient to titrate medication use as needed. We identified 40 patients with biopsy proven lichen sclerosus who had urethral stricture as part of the disease state. Of these patients 28 received the intraurethral steroid regimen and success was achieved in 25 (89%). Mean followup was 24.8 months. No patient who was started on the intraurethral steroid regimen proceeded to urethroplasty. Based on our outcomes we have developed a stepwise treatment algorithm for patients with biopsy proven lichen sclerosus stricture disease that uses intraurethral steroids before initiating plans for invasive surgery.

The FKBP5 polymorphism rs1360780 influences the effect of an algorithm-based antidepressant treatment and is associated with remission in patients with major depression.

The FKBP5-gene influences the HPA-system by modulating the sensitivity of the glucocorticoid receptor (GR). The polymorphism rs1360780 has been associated with response in studies with heterogeneous antidepressant treatment. In contrast, several antidepressant studies with standardized antidepressant treatment could not detect this effect. We therefore compared patients with standardized vs naturalistic antidepressant treatment to (a) investigate a possible interaction between FKBP5-genotype and treatment mode and (b) replicate the effect of the FKBP5-genotype on antidepressant treatment outcome. A total of 298 major depressive disorder (MDD) inpatients from the multicentred German project and the Zurich Algorithm Project were genotyped for their FKBP5 status. Patients were treated as usual (n=127) or according to a standardized algorithm (n=171). Main outcome criteria was remission (Hamilton Depression Rating Scale-21<10). We detected an interaction of treatment as usual (TAU) treatment and C-allele with the worst outcome for patients combining those two factors (HR=0.46; p=0.000). Even though C-allele patients did better when treated in the structured, stepwise treatment algorithm (SSTR) group, we still could confirm the influence of the FKBP5-genotype in the whole sample (HR=0.52; p=0.01). This is the first study to show an interaction between a genetic polymorphism and treatment mode. Patients with the C-allele of the rs1360780 polymorphism seem to benefit from a standardized antidepressant treatment.