Partial Response and Nonresponse to Antidepressant Therapy

Hirschfeld, Robert M. A.; Montgomery, Stuart; Aguglia, Eugenio; Amore, Mario; Delgado, Pedro L.; Gastpar, Markus; Hawley, Christopher J.; Kasper, S.; Lindén, Michael; Massana, Joan; Mendlewicz, Julien; Möller, Hans; Nemeroff, Charles B.; Sáiz, Jerónimo; Such, Pedro; Torta, Riccardo; Versiani, Márcio

doi:10.4088/jcp.v63n0913

Cited by 176 publications

(84 citation statements)

References 54 publications

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“…Remission of major depression is difficult to achieve for many patients and less than 50% of depressed patients will respond to standard treatments (Hirchfield et al, 2002;Keitner et al, 2006;Rush et al, 2004;Trivedi et al, 2006). Several treatment strategies are available for depressed patients who fail to respond, or only partially respond, to an adequate trial of antidepressant monotherapy but the next step after a failed adequate medication trial remains unclear (Keller, 2005;Nelson, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…An estimated 30-50% of depressed patients do not respond, or only partially respond, to an adequate treatment with antidepressant medication (Appelberg et al, 2001;Fava and Davidson, 1996;Fleck and Horwath, 2005;Hirchfield et al, 2002;Keitner et al, 2006;Rubio et al, 2004). Furthermore, rapid recovery of severe depression is the exception rather than the rule (Lewis, 2003).…”

Section: Introductionmentioning

confidence: 99%

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A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

Keitner

Garlow

Ryan

et al. 2009

Journal of Psychiatric Research

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Objective-Patients (30-50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication.Method-Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5-3 mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of ≤10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire.Results-Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR = 3.33, p = . 011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS ≤ 10) compared to 24% of the placebo augmentation group (CMH(1) = 6.48, p = .011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no betweengroup differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone. Conclusion-Augmentation of an antidepressant with risperidone for patients with difficult-totreat depression leads to more rapid response and a higher remission rate and better quality-of-life.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

Keitner

Garlow

Ryan

et al. 2009

Journal of Psychiatric Research

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“…[23] Response rates (including those who remitted) were 48.6, 28.5, 17.4, and 18.1% for Steps 1-4. [23] Recent reviews of depression and its treatment have either focused on the cost of illness of depression [24,25] or on clinical efficacy [26][27][28][29][30] or cost-effectiveness [31][32][33][34][35] of treatments for depression including depression that is not responsive to the initial treatment regimen. To supplement this literature, this review presents a summary of published data focused on the following two important questions:…”

Section: Introductionmentioning

confidence: 99%

Nonresponse, partial response, and failure to achieve remission: humanistic and cost burden in major depressive disorder

et al. 2009

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Objective: To characterize the spectrum of clinical outcomes achieved with depression treatment and the associated impact on quality of life (QOL), functional status, overall well-being, health-care costs, and productivity. Sources: Electronic databases including Medline were searched for English language sources between 1995 and 2007 using key words of depression, nonresponse, partial response, and remission and QOL, functional status, utility, cost, and productivity. Study selection: Relevant abstracts were obtained for 488 references and full-text articles were reviewed that included primary data and compared outcomes by treatment response. Data were abstracted from 26 full-text articles. Data abstraction: Detailed evidence tables were prepared with the relevant data as well as information on the study design. All data abstracted were checked for accuracy. Synthesis: Treatment remitters and partial responders reported clinically and statistically significant improvements in QOL, functional status, and overall well-being compared to nonresponders. Annual health-care costs and productivity losses were significantly lower for remitters and partial responders compared to nonresponders. Conclusions: The reduced disease burden for remitters and partial responders compared to nonresponders indicates that new treatment strategies that improve the rates of response/remission with initial treatment might have value to patients and to society. Depression and Anxiety 26:83-97, 2009.

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“…Patients who fail to achieve full remission have been shown to be at greater risk of subsequent relapse, recurrence, and chronicity [Judd et al, 2000;Paykel et al, 1995], and have impaired long-term social functioning [Kennedy and Paykel, 2004]. However, a substantial proportion of patients exhibit a suboptimal response to an initial course of antidepressant therapy [Hirschfeld et al, 2002]. Although switching or combination/augmentation strategies may eventually be considered for these patients, a first approach to managing patients with an inadequate treatment response is to increase the dose of the current medication [Hirschfeld et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

“…However, a substantial proportion of patients exhibit a suboptimal response to an initial course of antidepressant therapy [Hirschfeld et al, 2002]. Although switching or combination/augmentation strategies may eventually be considered for these patients, a first approach to managing patients with an inadequate treatment response is to increase the dose of the current medication [Hirschfeld et al, 2002]. The safety and tolerability profile associated with such a dose escalation is therefore of considerable interest for clinicians.…”

Section: Introductionmentioning

confidence: 99%

Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation

et al. 2006

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Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. To further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This singlearm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age Z18 years) meeting DSM-IV criteria for MDD (n 5 128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (Po.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by 410% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of...

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Partial Response and Nonresponse to Antidepressant Therapy

Cited by 176 publications

References 54 publications

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

Nonresponse, partial response, and failure to achieve remission: humanistic and cost burden in major depressive disorder

Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation

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