Background: There is a need for novel approaches to the treatment of stimulant abuse and dependen... more Background: There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction ...
BackgroundAttitudes and expectations about treatment have been associated with symptomatic outcom... more BackgroundAttitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available.MethodThe Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated.ResultsEvaluation of the ABC's internal consistency yielded Cronbach's α of 0.90–0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for al...
BackgroundPrior studies have suggested that major depressive disorder (MDD) with pre-adult onset ... more BackgroundPrior studies have suggested that major depressive disorder (MDD) with pre-adult onset represents a distinct subtype with greater symptom severity and higher rates of suicidal ideation. Whether these patients have poorer response to various types of antidepressant treatment than those with adult-onset MDD is unclear.MethodA total of 665 psychiatric and primary care out-patients (aged 18–75 years) with non-psychotic chronic or recurrent MDD participated in a single-blind, randomized trial that compared the efficacy of escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine. We compared participants who self-reported MDD onset (before age 18) to those with a later onset (adult onset) with respect to baseline characteristics and treatment/outcome variables at 12 and 28 weeks.ResultsEarly-onset chronic/recurrent MDD was associated with a distinct set of sociodemographic (female, younger age) and clinical correl...
Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and ma... more Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of side effects or the frequency, intensity, or burden of side effects, interventions to maximize retention could be focused on patients with these events. Outpatient participants (n=265) with nonpsychotic major depressive disorder entered an 8-week trial with an SSRI. At baseline and week 2, specific side effects were evaluated with the Systematic Assessment for Treatment Emergent Events – Systematic Inquiry, and at week 2 the Frequency, Intensity, and Burden of Side Effects Rating globally assessed side effects. Attrition was defined by those participants who left treatment after week 2 but before week 8. No specific week 2 side effect, either treatment emergent or with worsening intensity, was independently associated with attrition. Global ratings of side effect frequency, intensity, or bur...
To evaluate exercise as a treatment for stimulant use disorders. The STimulant Reduction Interven... more To evaluate exercise as a treatment for stimulant use disorders. The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks. The primary outcome of percent stimulant abstinent days during study weeks 4 to 12 was estimated using a novel algorithm adjustment incorporating self-reported Timeline Followback (TLFB) stimulant use and urine drug screen (UDS) data. Mean percent of abstinent days based on TLFB was 90.8% (SD = 16.4%) for Exercise and 91.6% (SD = 14.7%) for Health Education partic...
Missing data in substance use disorder (SUD) research pose a significant threat to internal valid... more Missing data in substance use disorder (SUD) research pose a significant threat to internal validity. Participants terminate involvement or become less likely to attend intervention and research visits for many reasons, which should be addressed prior to becoming problematic. During a 9-month study targeting stimulant abuse, early dropouts and participant reported attendance barriers led to implementing a structured, pre-randomization protocol with participants about retention and solution-focused strategies (the "Fireside Chat"). Our aim is to outline this approach and present data on intervention participation and research visit attendance after implementation. STimulant Reduction using Dosed Exercise (STRIDE) was a two-arm, multisite randomized clinical trial testing treatment-as-usual for stimulant abuse/dependence augmented by Exercise or Health Education. For both groups, study intervention visits at the site were scheduled 3/week for 12weeks followed by 1/week for 2...
This study aimed to determine if current comorbid psychiatric disorders differ in adults with coc... more This study aimed to determine if current comorbid psychiatric disorders differ in adults with cocaine use disorder, other stimulant (primarily methamphetamine) use disorder, or both, and identify demographic and clinical characteristics in those with increasing numbers of comorbid disorders. Baseline data from a randomized controlled trial beginning in residential settings (N=302) was used. Mood disorders were present in 33.6%, and anxiety disorders in 29.6%, with no differences among stimulant use disorder groups. Panic disorder was more frequently present with other stimulant use disorder. Those with two or more comorbid psychiatric disorders were more often female, White, had more symptoms of depression, greater propensity and risk for suicidal behavior, lower functioning in psychiatric and family domains, lower quality of life, more symptoms with stimulant abstinence and greater likelihood of marijuana dependence. Those with one or more comorbid disorders had more medical disord...
The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (ST... more The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a large-scale practical clinical trial to determine which of several treatments are the most effective "next-steps" for patients with major depressive disorder whose symptoms do not remit or who cannot tolerate an initial treatment and, if needed, ensuing treatments. Entry criteria were broadly defined and inclusive, and patients were enrolled from psychiatric and primary care clinics. All participants began on citalopram and were managed by clinic physicians, who followed an algorithm-guided acute-phase treatment through five visits over 12 weeks. At the end of each sequence, patients whose depression had not fully remitted were eligible for subsequent randomized trials in a sequence of up to three clinical trials. In general, remission rates in the study clinics were lower than expected, suggesting the need for several steps to achieve remission for most patients. There was no clear medication "winner" for patients whose depression did not remit after one or more aggressive medication trials. Both switching and augmenting appeared to be reasonable options when an initial antidepressant treatment failed, although these two strategies could not be directly compared. Further, the likelihood of remission after two vigorous medication trials substantially decreased, and remission would likely require more complicated medication regimens for which the existing evidence base is quite thin. STAR*D demonstrated that inclusion of more real-world patients in clinical trials is both feasible and informative. Policy implications of the findings, as well as the study's limitations, are discussed.
The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions, 2016
Rates of medical illnesses may be higher among individuals with substance use disorders, complica... more Rates of medical illnesses may be higher among individuals with substance use disorders, complicating their care. This study aimed to expand the understanding of other medical conditions in treatment-seeking adults with stimulant use disorder (SUD) using data from Stimulant Reduction Intervention using Dose Exercise (STRIDE), a randomized, multisite trial investigating exercise augmentation of treatment as usual. Utilizing STRIDE baseline data, we examined demographic and clinical characteristics based on the number of self-reported diagnosed medical conditions among participants meeting eligibility criteria (passing medical screening exam and maximal exercise test, non-opioid dependent, no concomitant beta blocker, or opioid replacement therapy). The majority (59%) of study participants (N = 302, mean age all participants = 39 years) did not report any history of other medical problems. Those with two or more conditions were older (mean age 46 years), reported more pain and worse p...
Although major depressive disorder (MDD) is associated with significant impairments in health-rel... more Although major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQOL), few studies have evaluated HRQOL dysfunction in multiple domains. This report examined the psychological, physical, and social domains in a large sample of outpatients who entered the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. The relationship of HRQOL and baseline sociodemographic and clinical features, including depressive severity, was evaluated. We assessed HRQOL with the 12-item Short Form Health Survey, the 5-item Work and Social Adjustment Scale, and the 16-item Quality of Life Enjoyment and Satisfaction Questionnaire. Among 2307 participants, greater depressive symptom severity was associated with poorer HRQOL. After controlling for age and depression severity, lower HRQOL was related independently to being African American or Hispanic, less educated, unemployed, divorced or separated, having public medical insurance, and to having more general medical disorders. We found impairments across all 3 domains, with low correlations between the 3 measures of HRQOL chosen, suggesting that they evaluate different and nonoverlapping aspects of function. Sociodemographically disadvantaged patients with greater general medical and depressive illness burden are at greatest risk for poorer quality of life. Distinct impairments are seen in the 3 domains of HRQOL.
The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequen... more The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequenced, randomized treatment trials following a first and, if needed, subsequent treatment steps to define the tolerability and effectiveness of various options in both acute and longer term treatment. Adult outpatients (n=4041) with nonpsychotic major depressive disorder, substantial chronic and recurrent depression, and co-morbid psychiatric and general medical conditions were enrolled in 41 representative primary and specialty care settings. About one-third of participants remitted in first step treatment with citalopram, 50% of these within 6 weeks. Poorer outcomes were associated with minority status, socioeconomic disadvantage, more axis I and III co-morbid disorders, lower function and quality of life, and anxious and melancholic features. In step 2 medication switch, there were no significant differences in remission among within-class, out-of-class or dual-action agents: sertraline (27%), bupropion-sustained release (26%) and venlafaxine-extended release (25%). In step 2 medication augmentation of citalopram, there was no significant difference in remission between bupropion-sustained release (39%) and buspirone (33%), although participants using bupropion-sustained release had greater symptom reduction and better tolerability. There were no significant differences in remission in step 2 between cognitive therapy and medication treatment in either the switch (31% vs 27%) or augmentation (31% vs 33%) strategies, although participants in cognitive therapy augmentation had a longer time to remission than those in medication augmentation (55 vs 40 days). In step 3, there were no differences in remission between a switch to mirtazapine (8%) or nortriptyline (12%), or between augmentation with lithium (13%) or T(3) (triiodothyronine, liothyronine) [25%], although more participants discontinued lithium due to adverse effects than discontinued T(3). In the fourth step, there was no difference in remission between tranylcypromine (14%) or venlafaxine-extended release plus mirtazapine (16%), although the combination treatment had fewer adverse effects and had the advantages of not requiring a washout period or diet restrictions. Participants requiring more than two well delivered treatments may be characterized as treatment resistant given the substantially lower remission rates after that point. Treatment resistance was associated with more concurrent axis I or III co-morbid conditions, socioeconomic disadvantage, chronicity and melancholic or anxious features. However, if participants remained in treatment for up to four steps, about 67% reached remission. Times to remission were not substantially longer for later treatment steps. The importance of reaching remission is highlighted by the lower relapse rates in naturalistic follow-up for participants entering in remission compared with those entering with response but not remission (step 1: 34% vs 59%; step 2: 47% vs 68%; step 3: 42% vs 76%; step 4: 50% vs 83%). Clinical decision making based on the itemized measurement of symptoms and adverse effects at each treatment visit was feasible in STAR*D's real world settings and resulted in adequate dosages and durations of treatment that generally exceeded those typically found in practice settings. Although switch and augmentation strategies could not be directly compared due to the equipoise stratified randomized design, the higher remission rates at step 2 with medication augmentation are intriguing and merit further study.
Background: There is a need for novel approaches to the treatment of stimulant abuse and dependen... more Background: There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction ...
BackgroundAttitudes and expectations about treatment have been associated with symptomatic outcom... more BackgroundAttitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available.MethodThe Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated.ResultsEvaluation of the ABC's internal consistency yielded Cronbach's α of 0.90–0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for al...
BackgroundPrior studies have suggested that major depressive disorder (MDD) with pre-adult onset ... more BackgroundPrior studies have suggested that major depressive disorder (MDD) with pre-adult onset represents a distinct subtype with greater symptom severity and higher rates of suicidal ideation. Whether these patients have poorer response to various types of antidepressant treatment than those with adult-onset MDD is unclear.MethodA total of 665 psychiatric and primary care out-patients (aged 18–75 years) with non-psychotic chronic or recurrent MDD participated in a single-blind, randomized trial that compared the efficacy of escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine. We compared participants who self-reported MDD onset (before age 18) to those with a later onset (adult onset) with respect to baseline characteristics and treatment/outcome variables at 12 and 28 weeks.ResultsEarly-onset chronic/recurrent MDD was associated with a distinct set of sociodemographic (female, younger age) and clinical correl...
Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and ma... more Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of side effects or the frequency, intensity, or burden of side effects, interventions to maximize retention could be focused on patients with these events. Outpatient participants (n=265) with nonpsychotic major depressive disorder entered an 8-week trial with an SSRI. At baseline and week 2, specific side effects were evaluated with the Systematic Assessment for Treatment Emergent Events – Systematic Inquiry, and at week 2 the Frequency, Intensity, and Burden of Side Effects Rating globally assessed side effects. Attrition was defined by those participants who left treatment after week 2 but before week 8. No specific week 2 side effect, either treatment emergent or with worsening intensity, was independently associated with attrition. Global ratings of side effect frequency, intensity, or bur...
To evaluate exercise as a treatment for stimulant use disorders. The STimulant Reduction Interven... more To evaluate exercise as a treatment for stimulant use disorders. The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks. The primary outcome of percent stimulant abstinent days during study weeks 4 to 12 was estimated using a novel algorithm adjustment incorporating self-reported Timeline Followback (TLFB) stimulant use and urine drug screen (UDS) data. Mean percent of abstinent days based on TLFB was 90.8% (SD = 16.4%) for Exercise and 91.6% (SD = 14.7%) for Health Education partic...
Missing data in substance use disorder (SUD) research pose a significant threat to internal valid... more Missing data in substance use disorder (SUD) research pose a significant threat to internal validity. Participants terminate involvement or become less likely to attend intervention and research visits for many reasons, which should be addressed prior to becoming problematic. During a 9-month study targeting stimulant abuse, early dropouts and participant reported attendance barriers led to implementing a structured, pre-randomization protocol with participants about retention and solution-focused strategies (the "Fireside Chat"). Our aim is to outline this approach and present data on intervention participation and research visit attendance after implementation. STimulant Reduction using Dosed Exercise (STRIDE) was a two-arm, multisite randomized clinical trial testing treatment-as-usual for stimulant abuse/dependence augmented by Exercise or Health Education. For both groups, study intervention visits at the site were scheduled 3/week for 12weeks followed by 1/week for 2...
This study aimed to determine if current comorbid psychiatric disorders differ in adults with coc... more This study aimed to determine if current comorbid psychiatric disorders differ in adults with cocaine use disorder, other stimulant (primarily methamphetamine) use disorder, or both, and identify demographic and clinical characteristics in those with increasing numbers of comorbid disorders. Baseline data from a randomized controlled trial beginning in residential settings (N=302) was used. Mood disorders were present in 33.6%, and anxiety disorders in 29.6%, with no differences among stimulant use disorder groups. Panic disorder was more frequently present with other stimulant use disorder. Those with two or more comorbid psychiatric disorders were more often female, White, had more symptoms of depression, greater propensity and risk for suicidal behavior, lower functioning in psychiatric and family domains, lower quality of life, more symptoms with stimulant abstinence and greater likelihood of marijuana dependence. Those with one or more comorbid disorders had more medical disord...
The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (ST... more The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a large-scale practical clinical trial to determine which of several treatments are the most effective "next-steps" for patients with major depressive disorder whose symptoms do not remit or who cannot tolerate an initial treatment and, if needed, ensuing treatments. Entry criteria were broadly defined and inclusive, and patients were enrolled from psychiatric and primary care clinics. All participants began on citalopram and were managed by clinic physicians, who followed an algorithm-guided acute-phase treatment through five visits over 12 weeks. At the end of each sequence, patients whose depression had not fully remitted were eligible for subsequent randomized trials in a sequence of up to three clinical trials. In general, remission rates in the study clinics were lower than expected, suggesting the need for several steps to achieve remission for most patients. There was no clear medication "winner" for patients whose depression did not remit after one or more aggressive medication trials. Both switching and augmenting appeared to be reasonable options when an initial antidepressant treatment failed, although these two strategies could not be directly compared. Further, the likelihood of remission after two vigorous medication trials substantially decreased, and remission would likely require more complicated medication regimens for which the existing evidence base is quite thin. STAR*D demonstrated that inclusion of more real-world patients in clinical trials is both feasible and informative. Policy implications of the findings, as well as the study's limitations, are discussed.
The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions, 2016
Rates of medical illnesses may be higher among individuals with substance use disorders, complica... more Rates of medical illnesses may be higher among individuals with substance use disorders, complicating their care. This study aimed to expand the understanding of other medical conditions in treatment-seeking adults with stimulant use disorder (SUD) using data from Stimulant Reduction Intervention using Dose Exercise (STRIDE), a randomized, multisite trial investigating exercise augmentation of treatment as usual. Utilizing STRIDE baseline data, we examined demographic and clinical characteristics based on the number of self-reported diagnosed medical conditions among participants meeting eligibility criteria (passing medical screening exam and maximal exercise test, non-opioid dependent, no concomitant beta blocker, or opioid replacement therapy). The majority (59%) of study participants (N = 302, mean age all participants = 39 years) did not report any history of other medical problems. Those with two or more conditions were older (mean age 46 years), reported more pain and worse p...
Although major depressive disorder (MDD) is associated with significant impairments in health-rel... more Although major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQOL), few studies have evaluated HRQOL dysfunction in multiple domains. This report examined the psychological, physical, and social domains in a large sample of outpatients who entered the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. The relationship of HRQOL and baseline sociodemographic and clinical features, including depressive severity, was evaluated. We assessed HRQOL with the 12-item Short Form Health Survey, the 5-item Work and Social Adjustment Scale, and the 16-item Quality of Life Enjoyment and Satisfaction Questionnaire. Among 2307 participants, greater depressive symptom severity was associated with poorer HRQOL. After controlling for age and depression severity, lower HRQOL was related independently to being African American or Hispanic, less educated, unemployed, divorced or separated, having public medical insurance, and to having more general medical disorders. We found impairments across all 3 domains, with low correlations between the 3 measures of HRQOL chosen, suggesting that they evaluate different and nonoverlapping aspects of function. Sociodemographically disadvantaged patients with greater general medical and depressive illness burden are at greatest risk for poorer quality of life. Distinct impairments are seen in the 3 domains of HRQOL.
The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequen... more The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequenced, randomized treatment trials following a first and, if needed, subsequent treatment steps to define the tolerability and effectiveness of various options in both acute and longer term treatment. Adult outpatients (n=4041) with nonpsychotic major depressive disorder, substantial chronic and recurrent depression, and co-morbid psychiatric and general medical conditions were enrolled in 41 representative primary and specialty care settings. About one-third of participants remitted in first step treatment with citalopram, 50% of these within 6 weeks. Poorer outcomes were associated with minority status, socioeconomic disadvantage, more axis I and III co-morbid disorders, lower function and quality of life, and anxious and melancholic features. In step 2 medication switch, there were no significant differences in remission among within-class, out-of-class or dual-action agents: sertraline (27%), bupropion-sustained release (26%) and venlafaxine-extended release (25%). In step 2 medication augmentation of citalopram, there was no significant difference in remission between bupropion-sustained release (39%) and buspirone (33%), although participants using bupropion-sustained release had greater symptom reduction and better tolerability. There were no significant differences in remission in step 2 between cognitive therapy and medication treatment in either the switch (31% vs 27%) or augmentation (31% vs 33%) strategies, although participants in cognitive therapy augmentation had a longer time to remission than those in medication augmentation (55 vs 40 days). In step 3, there were no differences in remission between a switch to mirtazapine (8%) or nortriptyline (12%), or between augmentation with lithium (13%) or T(3) (triiodothyronine, liothyronine) [25%], although more participants discontinued lithium due to adverse effects than discontinued T(3). In the fourth step, there was no difference in remission between tranylcypromine (14%) or venlafaxine-extended release plus mirtazapine (16%), although the combination treatment had fewer adverse effects and had the advantages of not requiring a washout period or diet restrictions. Participants requiring more than two well delivered treatments may be characterized as treatment resistant given the substantially lower remission rates after that point. Treatment resistance was associated with more concurrent axis I or III co-morbid conditions, socioeconomic disadvantage, chronicity and melancholic or anxious features. However, if participants remained in treatment for up to four steps, about 67% reached remission. Times to remission were not substantially longer for later treatment steps. The importance of reaching remission is highlighted by the lower relapse rates in naturalistic follow-up for participants entering in remission compared with those entering with response but not remission (step 1: 34% vs 59%; step 2: 47% vs 68%; step 3: 42% vs 76%; step 4: 50% vs 83%). Clinical decision making based on the itemized measurement of symptoms and adverse effects at each treatment visit was feasible in STAR*D's real world settings and resulted in adequate dosages and durations of treatment that generally exceeded those typically found in practice settings. Although switch and augmentation strategies could not be directly compared due to the equipoise stratified randomized design, the higher remission rates at step 2 with medication augmentation are intriguing and merit further study.
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