Dataset Information

Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study.

ABSTRACT: The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double-blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18-70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients were required to be taking an allowed antidepressant for at least four weeks prior to screening. Patients were randomized equally to receive 15 double-blind intravenous infusions of adjunctive lanicemine 50?mg, lanicemine 100?mg, or saline over a 12-week course, in addition to ongoing antidepressant. The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6. Secondary efficacy outcome variables included change in MADRS score from baseline to week 12, response and remission rates, and changes in Clinical Global Impression scale, Quick Inventory of Depressive Symptomology Self-Report score, and Sheehan Disability Scale score. Of 302 randomized patients, 240 (79.5%) completed treatment. Although lanicemine was generally well tolerated, neither dose was superior to placebo in reducing depressive symptoms on the primary end point or any secondary measures. There was no significant difference between lanicemine and placebo treatment on any outcome measures related to MDD. Post hoc analyses were performed to explore the possible effects of trial design and patient characteristics in accounting for the contrasting results with a previously reported trial.

SUBMITTER: Sanacora G

PROVIDER: S-EPMC5312066 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study.

Sanacora Gerard G Johnson Michael R MR Khan Arif A Atkinson Sarah D SD Riesenberg Robert R RR Schronen Juan P JP Burke Michael A MA Zajecka John M JM Barra Luis L Su Hong-Lin HL Posener Joel A JA Bui Khanh H KH Quirk Michael C MC Piser Timothy M TM Mathew Sanjay J SJ Pathak Sanjeev S

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20160929 4

The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double-blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18-70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients ...[more]

PMID: 27681442

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Project description:IntroductionPatients with major depressive disorder (MDD) often fail to respond to first-line antidepressant treatments (ADTs); subsequent strategies include dosage increase, switch to a different ADT, or addition of another ADT or other drug. The objective of this prospective, case review study was to identify factors that influence the decision to prescribe adjunctive antipsychotics for patients with MDD and inadequate response to ADT.MethodsPsychiatrists or primary care physicians (n=411) based in the USA and Europe each completed an online survey for ten consecutive adults with MDD and inadequate response to ADTs, and for whom a treatment change was considered. A t test was used to compare survey responses between groups of patients.ResultsThe survey was completed for 4018 patients; an adjunctive antipsychotic was considered for 961/4018 patients (23.9%) and actually prescribed for 514/4018 (12.8%). Compared with patients not considered for an adjunctive antipsychotic, those who were considered for this treatment had more previous major depressive episodes (MDEs), longer duration of the current MDE, more severe illness both at ADT initiation and current consultation, and more treatment changes. Patients who were prescribed adjunctive antipsychotics had at baseline more functional impairment and absences from work than those considered for but not prescribed this treatment. Key symptoms that prompted physicians to consider antipsychotics were psychotic symptoms, psychomotor agitation, hostility, irritability, impulsivity, and anger bursts. Anxious mood and irritability were mentioned significantly more often by physicians who actually prescribed adjunctive antipsychotics. Obstacles to prescribing included a tendency to wait to see if symptoms improved and concern over side effects.ConclusionThis real-world study suggested that the decision to prescribe an adjunctive antipsychotic for patients with MDD and inadequate response to ADT is influenced by a broad spectrum of factors, predominantly related to severity of illness, functional impairment, and symptom profile.FundingOtsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, USA) and H. Lundbeck A/S (Valby, Denmark).

Project description:ObjectivePatients with major depressive disorder (MDD) with inadequate response to antidepressant treatment (ADT) may suffer a prolonged loss of functioning. This review aimed to determine if self-rated functional measures are informative in randomized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT.MethodsThis was a systematic literature review of articles in any language from the MEDLINE database published between January 1990 and March 2017. Eligible studies met the following criteria: patients with MDD; inadequate response to at least one ADT; adjunctive therapy (pharmacological or otherwise) to ADT; placebo control group; randomized controlled trial or a post hoc analysis of a randomized controlled trial; reported a self-rated functioning scale. Study characteristics and functioning efficacy data were extracted.ResultsA total of 2,090 discrete records were screened, 293 full-text articles were assessed for eligibility, and 26 studies were included. All studies were acute (6-12 weeks) except for one 52-week study. The only self-rated functioning scale used in the included studies was the Sheehan Disability Scale (SDS). Of the 13 adjunctive agents identified, aripiprazole, brexpiprazole, edivoxetine, and risperidone improved functioning versus placebo (p<0.05), as measured by the SDS total or mean score. On the SDS "work/studies" item, only aripiprazole had a statistically significant benefit, in one study out of four. Thus, where a benefit was observed on the SDS total or mean, this was generally driven by improvement on the "social life" and "family life" items. A limitation of the review is that it only considered published literature from one database.ConclusionThe SDS, a self-rated functional measure, is informative in acute randomized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT. However, the item that measures work performance may be less relevant to this population than the items that measure social and family life.

Project description:ObjectiveEpisodes of major depressive disorder (MDD) characterized by high levels of anxiety symptoms are less likely to respond to some forms of antidepressant treatment (ADT). This report examines the effects of adjunctive brexpiprazole on depressive symptoms among patients with MDD and anxiety symptoms.Materials and methodsThis was a post hoc analysis of 1,171 patients from the 6-week, randomized, double-blind phases of three studies in adults with MDD and inadequate response to ADTs (NCT01360645, NCT01360632, NCT02196506). Data were pooled for brexpiprazole 2-3 mg/day and for placebo (adjunct to ADT). Montgomery-Åsberg Depression Rating Scale Total score changes were assessed in subgroups of patients with and without anxious distress (based on proxies for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria) and anxious depression (defined as a Hamilton Depression Rating Scale Anxiety/somatization factor score of ?7). Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs).ResultsBenefits were seen for adjunctive brexpiprazole (compared with adjunctive placebo) in both anxiety definition subgroups. For patients with anxious distress, the least squares mean difference (95% CI) at week 6 was -3.00 (-4.29, -1.71; P<0.0001) and, for those without anxious distress, was -1.38 (-2.71, -0.05; P=0.043). For patients with anxious depression, the difference was -2.19 (-3.60, -0.78; P=0.0023), compared with -2.34 (-3.58, -1.10; P=0.0002) for those without anxious depression. The most common TEAEs among patients with anxiety symptoms receiving ADT + brexpiprazole were akathisia, headache, restlessness, somnolence, and weight increase. There were no clinically meaningful differences in the rates of these TEAEs according to the presence or absence of anxiety symptoms.ConclusionAdjunctive brexpiprazole 2-3 mg/day may be efficacious in reducing depressive symptoms, and was well tolerated, in patients with clinically relevant anxiety symptoms.

Dataset Information

Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study.

Publications

Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study.

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