The STAR*D Project results: A comprehensive review of findings

Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9086, USA.
Current Psychiatry Reports (Impact Factor: 3.24). 01/2008; 9(6):449-59. DOI: 10.1007/s11920-007-0061-3
Source: PubMed


The Sequenced Treatment Alternatives to Relieve Depression trial enrolled outpatients with nonpsychotic major depressive disorder treated prospectively in a series of randomized controlled trials. These were conducted in representative primary and psychiatric practices. Remission rates for treatment steps 1 to 4 based on the 16-item Quick Inventory of Depressive Symptomatology-Self-report were 37%, 31%, 14%, and 13%, respectively. There were no differences in remission rates or times to remission among medication switch or among medication augmentation strategies at any treatment level. Participants who required increasing numbers of treatment steps showed greater depressive illness burden and increasingly greater relapse rates in the naturalistic follow-up period (40%-71%). Prognosis was better at all levels for participants who entered follow-up in remission as opposed to those who entered with response without remission. These results highlight the prevalence of treatment-resistant depression and suggest potential benefit for using more vigorous treatments in the earlier steps.

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Available from: Madhukar H Trivedi,
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    • "The STAR*D research program, for example, used an equipoised stratified randomized design and gave each patient the possibility to accept the assignment to a particular treatment strategy (e.g., pharmacotherapy and CBT) or decline it and to move to another study arm. This procedure was intended to be more close to what happens in routine care and to reduce the number of non-consenters, resulting in a higher external validity of the study's findings (Warden et al., 2007). "
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    ABSTRACT: Background: The efficacy of cognitive behavioral therapy (CBT) for the treatment of depressive disorders has been demonstrated in many randomized controlled trials (RCTs). This study investigated whether for CBT similar effects can be expected under routine care conditions when the patients are comparable to those examined in RCTs. Method: N=574 CBT patients from an outpatient clinic were stepwise matched to the patients undergoing CBT in the National Institute of Mental Health Treatment of Depression Collaborative Research Program (TDCRP). First, the exclusion criteria of the RCT were applied to the naturalistic sample of the outpatient clinic. Second, propensity score matching (PSM) was used to adjust the remaining naturalistic sample on the basis of baseline covariate distributions. Matched samples were then compared regarding treatment effects using effect sizes, average treatment effect on the treated (ATT) and recovery rates. Results: CBT in the adjusted naturalistic subsample was as effective as in the RCT. However, treatments lasted significantly longer under routine care conditions. Limitations: The samples included only a limited amount of common predictor variables and stemmed from different countries. There might be additional covariates, which could potentially further improve the matching between the samples. Conclusions: CBT for depression in clinical practice might be equally effective as manual-based treatments in RCTs when they are applied to comparable patients. The fact that similar effects under routine conditions were reached with more sessions, however, points to the potential to optimize treatments in clinical practice with respect to their efficiency.
    Journal of Affective Disorders 09/2015; 189. DOI:10.1016/j.jad.2015.08.072 · 3.38 Impact Factor
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    • "Additionally, non-steroidal anti-inflammatory drugs might be beneficial as adjunctive treatments in unipolar (Akhondzadeh et al., 2009; Muller et al., 2006) and bipolar (Nery et al., 2008) disorders and the TNFα antagonist infliximab may particularly benefit depressed individuals with a history of treatment resistance and high inflammation (Raison et al., 2013). Treatment non-response contributes greatly to the burden of affective illnesses (Gibson et al., 2010); it is common, affecting at least a third of patients (Warden et al., 2007), and is generally associated with poorer long-term outcomes (Fekadu et al., 2009). To improve the rate and robustness of clinical response in depression there is a need for novel treatment strategies (Kupfer et al., 2012), including enhancing the personalisation of treatment provision using stratification . "
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    ABSTRACT: The depressive state has been characterised as one of elevated inflammation, which holds promise for better understanding treatment-resistance in affective disorders as well as for future developments in treatment stratification. Aiming to investigate alterations in the inflammatory profiles of individuals with depression as putative biomarkers for clinical response, we conducted a meta-analyses examining data from 35 studies that investigated inflammation before and after treatment in depressed patients together with a measure of clinical response. There were sufficient data to analyse IL-6, TNFα and CRP. Levels of IL-6 decreased with antidepressant treatment regardless of outcome, whereas persistently elevated TNFα was associated with prospectively determined treatment resistance. Treatment non-responders tended to have higher baseline inflammation, using a composite measure of inflammatory markers. Our findings suggest that elevated levels of inflammation are contributory to treatment resistance. Combining inflammatory biomarkers might prove a useful tool to improve diagnosis and detection of treatment refractoriness, and targeting persistent inflammation in treatment-resistant depression may offer a potential target for the development of novel intervention strategies. Copyright © 2015. Published by Elsevier B.V.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2015; 25(10). DOI:10.1016/j.euroneuro.2015.06.007 · 4.37 Impact Factor
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    • "First line therapy for major depressive disorder relies on the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinepherine reuptake inhibitors (SNRIs) (Rush et al. 2006; Gelenberg et al. 2010). Although SSRIs and SNRIs have dramatically expanded treatment options for major depressive disorder, there is still a significant unmet medical need for management of this disorder, including therapeutics delayed onset, and treatment resistance (Rush et al. 2006; Warden et al. 2007; Reeves et al. 2008; Gelenberg et al. 2010). It has been reported that pindolol, a 5-HT 1A/1B and b adrenergic receptor partial agonist, may accelerate antidepressants onset and enhance SSRIs beneficial effects in treatment-resistant depression. "
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    ABSTRACT: Enhancement of serotonergic neurotransmission has been the main stream of treatment for patients with depression. However, delayed therapeutic onset and undesirable side effects are major drawbacks for conventional serotonin reuptake inhibitors. Here, we show that DSP-1053, a novel serotonin reuptake inhibitor with 5-HT1A partial agonistic activity, displays fast antidepressant efficacy with minimal undesirable effects, especially nausea and emesis in animal models. DSP-1053 bound human serotonin transporter and 5-HT1A receptor with the Ki values of 1.02 ± 0.06 and 5.05 ± 1.07 nmol/L, respectively. This compound inhibited the serotonin transporter with an IC50 value of 2.74 ± 0.41 nmol/L and had an intrinsic activity for 5-HT1A receptors of 70.0 ± 6.3%. In rat microdialysis, DSP-1053, given once at 3 and 10 mg kg−1, dose-dependently increased extracellular 5-HT levels. In the rat forced swimming test, 2-week administration of DSR-1053 (1 mg kg−1) significantly reduced rats immobility time after treatment, whereas paroxetine (3 and 10 mg kg−1) required 3-week administration to reduce rats immobility time. In olfactory bulbectomy model, 1- and 2-week administration of DSP-1053 reduced both of emotional scores and activity in the open field, whereas paroxetine required 2 weeks to show similar beneficial effects. Although single administration of DSP-1053-induced emesis and vomiting in the rat and Suncus murinus, multiple treatment with this compound, but not with paroxetine, decreased the number of vomiting episodes. These results highlight the important role of 5-HT1A receptors in both the efficacy and tolerability of DSP-1053 as a new therapeutic option for the treatment of depression.
    06/2015; 3(3). DOI:10.1002/prp2.142
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