quetiapine-fumarate and Depressive-Disorder--Treatment-Resistant

Objective Augmentation of antidepressants with atypical antipsychotics is used in depressive patients with non-response to antidepressants. We investigated the utility of this strategy.Methods Systematic computer-based search in the online library Pubmed for randomized placebo-controlled double-blind trials (RCT) from the years 1990 to 2011.Results We found 14 RCT about augmentation of antidepressants with atypical antipsychotics in depressive patients with non-response to antidepressants. Trials examined olanzapine, risperidone, quetiapine and aripiprazole.Conclusions Augmentation of antidepressants with atypical antipsychotics is an alternative to the augmentation with lithium in unipolar depressive patients with non-response to antidepressants. But treatment with atypical antipsychotics as opposed to placebo increases the risk of non-compliance due to side-effects of medication. Augmentation of antidepressants with atypical antipsychotics in unipolar depression is an off-label therapy in Germany except for the augmentation with extended-release quetiapine. Knowledge about treatment strategies regarding augmentation of antidepressants with atypical antipsychotics can increase the chance of a successful treatment, but interactions and side-effects should be considered.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Treatment-Resistant; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium Carbonate; Olanzapine; Patient Compliance; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone

In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown.. In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures.. Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P = 0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments.. In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.).

Topics: Antidepressive Agents; Delayed-Action Preparations; Depression; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Humans; Ketamine; Nasal Sprays; Quetiapine Fumarate; Recurrence; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Single-Blind Method; Treatment Outcome

Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group.. The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects.. The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies.. ISRCTN registry: ISRCTN16387615 , registered 28 February 2016. ClinicalTrials.gov: NCT03004521 , registered 17 November 2016.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Cost-Benefit Analysis; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Humans; Lithium; Quetiapine Fumarate

Approximately 50% of patients with major depressive disorder do not respond adequately to their antidepressant treatment, underscoring the need for more effective treatment options. The objective of this study was to investigate the effect of adjunctive brexpiprazole on depressive symptoms in patients with major depressive disorder who were not responding to adjunctive or combination therapy of their current antidepressant treatments with several different classes of agents (NCT02012218).. In this 6-week, open-label, phase 3b study, patients with major depressive disorder who had an inadequate response to ≥1 adjunctive or combination therapy, in addition to history of ≥1 failure to monotherapy antidepressant treatment, were switched to adjunctive brexpiprazole. Efficacy was assessed by change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score. Patient functioning was assessed using the Sheehan Disability Scale and the Cognitive and Physical Functioning Questionnaire. Safety and tolerability were also assessed.. A total of 51/61 (83.6%) patients completed 6 weeks of treatment with adjunctive brexpiprazole. Improvements in depressive symptoms were observed (least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score, -17.3 [P < .0001]) as well as improvements in general and cognitive functioning (mean changes from baseline to week 6: Sheehan Disability Scale, -3.1 [P < .0001]; Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire, -9.2 [P < .0001]). The most common adverse event was fatigue (14.8%); akathisia was reported by 8.2% of patients.. In patients with major depressive disorder who had switched to open-label adjunctive brexpiprazole following inadequate response to previous adjunctive or combination therapy, improvements were observed in depressive symptoms, general functioning, cognitive function, and energy/alertness.

Topics: Antidepressive Agents; Aripiprazole; Bupropion; Central Nervous System Stimulants; Cognition; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Female; Humans; Impulsive Behavior; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Quinolones; Sleep; Thiophenes; Treatment Outcome

Patients with treatment-resistant major depressive disorder (MDD) remain a common clinical challenge.. This 6-week, randomised, open-label, rater-blinded trial evaluated once-daily extended-release quetiapine fumarate (quetiapine XR; 300 mg/day) as add-on to ongoing antidepressant and quetiapine XR monotherapy (300 mg/day) compared with add-on lithium (0.6-1.2 mmol/L) in patients with treatment-resistant MDD. Primary efficacy measure: change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomisation to week 6 with a pre-specified non-inferiority limit of 3 points on the MADRS.. At week 6, both add-on quetiapine XR (n=231) and quetiapine XR monotherapy (n=228) were non-inferior to add-on lithium (n=229); least squares means (LSM) differences (97.5% CI) in MADRS total score changes were -2.32 (-4.6, -0.05) and -0.97 (-3.24, 1.31), respectively. LSM MADRS total score change was numerically greater at day 4 for both quetiapine XR groups (add-on and monotherapy; p<0.01) compared with add-on lithium. At week 6, the differences between groups for the secondary endpoints of MADRS response (≥ 50% reduction in total score), MADRS remission (total score ≤ 10, add-on quetiapine XR only) and Clinical Global Impressions ('much'/'very much' improved) were numerically similar. Overall tolerability was consistent with the known profiles of both treatments.. Limitations included the open-label study design (although MADRS and laboratory measurements were performed by treatment-blinded raters) and relatively short study duration with no assessments in the continuation phase.. Add-on quetiapine XR (300 mg/day) and quetiapine XR monotherapy (300 mg/day) are non-inferior to add-on lithium in the management of patients with treatment-resistant MDD.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lithium; Lithium Compounds; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Young Adult

Topics: Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Humans; Ketamine; Quetiapine Fumarate; Treatment Outcome

Treatment-resistant depression (TRD) has a profound cost to patients and healthcare services worldwide. Pharmacological augmentation is one therapeutic option for TRD, with lithium and quetiapine currently recommended as first-line agents. Patient opinions about pharmacological augmentation may affect treatment outcomes, yet these have not been systematically explored.. This study aimed to qualitatively assess patient experiences of lithium and quetiapine augmentation.. Semi-structured interviews were conducted with 32 patients from the ongoing lithium versus quetiapine open-label trial comparing these augmentation agents in patients with TRD. Interviews were audio recorded, transcribed and a thematic analysis was used to assess patient opinions of each agent.. Four main themes were generated from the thematic analysis: 'Initial concerns', 'Experience of side effects', 'Perception of treatment efficacy' and 'Positive perception of treatment monitoring'. Patient accounts indicated a predominantly positive experience of lithium and quetiapine augmentation. Greater apprehension about side effects was reported for lithium prior to treatment initiation, but greater experience of negative side effects was reported for quetiapine. Clinical monitoring was perceived positively.. Patient accounts suggested treatment augmentation with lithium or quetiapine was acceptable and helpful for most patients. However, anticipation and experiences of adverse side effects may prevent some patients from benefitting from these treatments.

Topics: Antidepressive Agents; Antipsychotic Agents; Depression; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Humans; Lithium; Quetiapine Fumarate; Treatment Outcome

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Treatment-Resistant; Drug Interactions; Drug Therapy, Combination; Fluoxetine; Humans; Ketamine; Lithium Compounds; Lorazepam; Middle Aged; Quetiapine Fumarate

Topics: Antimanic Agents; Antipsychotic Agents; Depressive Disorder, Treatment-Resistant; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Edema; Female; Humans; Lower Extremity; Medication Therapy Management; Middle Aged; Pharmacovigilance; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Valproic Acid