quetiapine-fumarate and Depressive-Disorder--Major

Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy.. A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events.. Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13,. Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Humans; Olanzapine; Quetiapine Fumarate; Risperidone

Quetiapine is a common off-label antipsychotic drug for treating insomnia. Its effects in different disease conditions and dosages remain unclear. We conducted a systematic review and meta-analysis in clinical trials examining the efficacy of low-dose quetiapine in sleep. We obtained 21 clinical trials. Mean difference (MD), standard mean difference (SMD), and odds ratio (OR) were used to estimate the effect sizes using a random-effects model. The pooled results showed that quetiapine improved sleep quality compared with placebo (SMD: -0.57 [95%CI: -0.75, -0.4]). The SMD of sleep quality was correlated with age (coefficient: -0.0174) and sex (coefficient: -0.012). The significant effects were observed in the general anxiety disorder (SMD: -0.59 [95%CI: -0.92, -0.27]), major depressive disorder (SMD: -0.47 [95%CI: -0.66, -0.28]), and healthy (SMD: -1.33, [95%CI [-2.12, -0.54]) subgroups, at the dosage of 50 mg (SMD: -0.36 [95%CI: -0.36, -0.11]), 150 mg (SMD: -0.4 [95%CI: -0.52, -0.29]), and 300 mg (SMD: -0.17 [95%CI: -0.31,-0.04]). Quetiapine increased total sleep time compared with placebo (MD: 47.91 [95%CI: 28.06, 67.76]) but not when compared with other psychiatric drugs (MD: -4.19 [95%CI: -19.43, 11.05]). Adverse events (AEs) and discontinuation due to AEs were common among the quetiapine users. Quetiapine is effective as a sleep-helping drug. Precaution is suggested when interpreting the results on the elderly due to the high heterogeneity caused by incorporating patients over 66 years in the meta-analyses. We recommend an initial dosage of 50-150 mg/day with priority consideration for the elderly with GAD or MDD while monitoring its potential AEs.

Topics: Aged; Antipsychotic Agents; Anxiety Disorders; Depressive Disorder, Major; Humans; Quetiapine Fumarate; Sleep

Treatment-resistant depression (TRD) affects one in three patients with major depressive disorder and is associated with increased risk of all-cause mortality. Studies of real-world practices suggest that antidepressant monotherapy continues to be the most widely used treatment after inadequate response to a first-line treatment. However, rates of remission with antidepressants in TRD are suboptimal. Atypical antipsychotics are the most widely studied augmentation agent and aripiprazole, brexpiprazole, cariprazine, quetiapine extended-release, and olanzapine-fluoxetine combination are approved for depression. Benefits of using atypical antipsychotics for TRD has to be weighted against their potential adverse events, such as weight gain, akathisia, and tardive dyskinesia.

Topics: Antidepressive Agents; Antipsychotic Agents; Depression; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Quetiapine Fumarate

Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD.. We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model.. 56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low.. Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Adult; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate

Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04-1.73 and 1.07-1.67, respectively] to 2.17 for risperidone (95% CrI 1.38-3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96-1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50-0.91), brexpiprazole (OR 0.69, 95% CrI 0.55-0.86), and cariprazine (OR 0.61, 95% CrI 0.46-0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25-1.07) and risperidone (OR 0.48, 95% CrI 0.10-2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.

Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate; Risperidone

Bupropion (BUP) is a norepinephrine-dopamine reuptake inhibitor frequently used in prisons. Although its positive effects on depression treatment are often presented, there are many questions about its approved use in prisons and similar facilities. In this context, this article aims to present two case reports of BUP XL unapproved use and a review of the mechanism of action, formulations, and the clinical profile of BUP.. Two case reports. The patients' data for the case reports were obtained from their medical records. A PubMed search was conducted using the terms BUP, inmates, and efficacy to identify randomized and non-randomized controlled trials and case reports to evaluate the possible effects of BUP in prison settings. Only approved medications were included.. The positive effects of BUP XL on major depressive disorder treatment are well-reported, but few reports are on the pharmacokinetics of BUP XL in prisons. The exact mechanism of its effect on the central nervous system is predominantly connected with its unique pharmacokinetics.. This paper shows that BUP XL will continue to play an essential role in treating a major depressive disorder in adults in prisons and other related disorders, although a different treatment strategy should be preferred in patients with high addictive potential. Because of a similar mechanism of action, the most appropriate alternatives for BUP XL could be mirtazapine, agomelatine, aripiprazole, and quetiapine, although clinical trials are needed to confirm these alternatives.

Topics: Adult; Aripiprazole; Bupropion; Depressive Disorder, Major; Dopamine; Humans; Mirtazapine; Norepinephrine; Prisons; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Topics: Adult; Antipsychotic Agents; Behavior, Addictive; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Prescription Drug Misuse; Quetiapine Fumarate; Substance-Related Disorders

Brexpiprazole is a new atypical antipsychotic for schizophrenia management and as adjunct in major depressive disorder (MDD). We searched randomized controlled trials (RCT) to review brexpiprazole efficacy and tolerability in acute management of schizophrenia and MDD using PubMed, EUDRACT, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials. A meta-analysis was conducted using the identified 14 RCT to assess its efficacy using positive and negative syndrome scale (PANSS), clinical global impressions - severity of illness (CGI-S), personal and social performance scale (PSP), Montgomery-Åsberg depression rating scale (MADRS), Sheehan disability scale (SDS) and Hamilton depression rating scale (HDRS17). The mean difference comparing brexpiprazole and placebo were PANSS -4.48, CGI-S -0.23 and PSP 3.24 favoring brexpiprazole. Compared to aripiprazole and quetiapine, brexpiprazole showed similar efficacy. In MDD, brexpiprazole showed efficacy compared to placebo demonstrated by MADRS -1.25, SDS -0.37 and HDRS17 -1.28. Brexpiprazole was associated with side effects including akathisia risk ratio (RR) = 1.72; weight increase RR = 2.74 and somnolence RR = 1.87. Compared to 4 mg, brexpiprazole 2 mg was associated with less risk of akathisia and somnolence. Brexpiprazole demonstrated significant improvements in schizophrenia and MDD and is well-tolerated; however, associated with akathisia and somnolence. These findings will guide psychiatrists and pharmacists in their clinical role for supporting psychiatric patients care.

Topics: Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Quinolones; Schizophrenia; Thiophenes; Treatment Outcome

Melancholic depression may preferentially respond to certain treatments. This study examined the efficacy of extended-release quetiapine monotherapy in patients with melancholic and nonmelancholic major depressive disorder.. Data from four randomized placebo-controlled trials was pooled. Melancholic features were assessed with baseline depression scale items according to DSM criteria. The outcome measure was response on the Montgomery-Åsberg Depression Rating Scale. Cox regression models predicting response over time with interactions between treatment condition and melancholic status were used to test for treatment effect heterogeneity.. The 6-week response rate difference between quetiapine and placebo was roughly 10% greater in the melancholic subgroup, primarily due to a lower placebo response, although the subgroup-treatment interactions did not reach statistical significance. The main effect of quetiapine was significant in every model.. The main limitations were the retrospective analysis and the post-hoc designation of melancholic depression based on scale items not designed for that purpose. Results should be considered preliminary and exploratory until replicated.. The lower placebo response rate in the melancholic subgroup is consistent with past research and reinforces the benefit of pharmacotherapy for these patients.

Topics: Antipsychotic Agents; Depression; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome

Major depressive disorder (MDD) is a highly debilitating condition that is drawing considerable attention due to its high global prevalence and to the fact that treatments are still far from reaching the total number of patients affected. Among available treatment strategies, quetiapine is an important research target, due to antidepressant responses in patients resistant to classical treatments and in animals submitted to protocols that induce depressive-like behaviours. Quetiapine has a broad spectrum of action, within which are many mechanisms that seem to be related to the most effective antidepressant therapeutic responses. In this review, research results related to the pharmacokinetic profile, neurotransmitters, receptors and signalling molecular targets involved in the functional and structural plasticity of key brain regions in MDD are reported and discussed. Moreover, the physiological mechanisms, which are targets of quetiapine and are involved in both MDD and poor therapeutic response, are reported. The main adverse effects observed from therapeutic dosages and overdose are also described. Finally, the main mechanisms underlying the therapeutic response are highlighted.

Topics: Animals; Antidepressive Agents; Depressive Disorder, Major; Humans; Neuronal Plasticity; Quetiapine Fumarate

This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states.. The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.. The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines.. The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Thiazoles; Valproic Acid

This is an update of the original Cochrane Review, last published in 2012 (Loy 2012). Children and youths with disruptive behaviour disorders may present to health services, where they may be treated with atypical antipsychotics. There is increasing usage of atypical antipsychotics in the treatment of disruptive behaviour disorders.. To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. The aim was to evaluate each drug separately rather than the class effect, on the grounds that each atypical antipsychotic has different pharmacologic binding profile (Stahl 2013) and that this is clinically more useful.. In January 2017, we searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers.. Randomised controlled trials of atypical antipsychotics versus placebo in children and youths aged up to and including 18 years, with a diagnosis of disruptive behaviour disorders, including comorbid ADHD. The primary outcomes were aggression, conduct problems and adverse events (i.e. weight gain/changes and metabolic parameters). The secondary outcomes were general functioning, noncompliance, other adverse events, social functioning, family functioning, parent satisfaction and school functioning.. We used standard methodological procedures expected by Cochrane. Two review authors (JL and KS) independently collected, evaluated and extracted data. We used the GRADE approach to assess the quality of the evidence. We performed meta-analyses for each of our primary outcomes, except for metabolic parameters, due to inadequate outcome data.. We included 10 trials (spanning 2000 to 2014), involving a total of 896 children and youths aged five to 18 years. Bar two trials, all came from an outpatient setting. Eight trials assessed risperidone, one assessed quetiapine and one assessed ziprasidone. Nine trials assessed acute efficacy (over four to 10 weeks); one of which combined treatment with stimulant medication and parent training. One trial was a six-month maintenance trial assessing symptom recurrence.The quality of the evidence ranged from low to moderate. Nine studies had some degree of pharmaceutical support/funding. Primary outcomesUsing the mean difference (MD), we combined data from three studies (238 participants) in a meta-analysis of aggression, as assessed using the Aberrant Behaviour Checklist (ABC) ‒ Irritability subscale. We found that youths treated with risperidone show reduced aggression compared to youths treated with placebo (MD -6.49, 95% confidence interval (CI) -8.79 to -4.19; low-quality evidence). Using the standardised mean difference (SMD), we pooled data from two risperidone trials (190 participants), which used different scales: the Overt Aggression Scale ‒ Modified (OAS-M) Scale and the Antisocial Behaviour Scale (ABS); as the ABS had two subscales that could not be combined (reactive and proactive aggression), we performed two separate analyses. When we combined the ABS Reactive subscale and the OAS-M, the SMD was -1.30 in favour of risperidone (95% CI -2.21 to -0.40, moderate-quality evidence). When we combined the ABS Proactive subscale and OAS-M, the SMD was -1.12 (95% CI -2.30 to 0.06, moderate-quality evidence), suggesting uncertainty about the estimate of effect, as the confidence intervals overlapped the null value. In summary, there was some evidence that aggression could be reduced by risperidone. Data were lacking on other atypical antipsychotics, like quetiapine and ziprasidone, with regard to their effects on aggression.We pooled data from two risperidone trials (225 participants) in a meta-analysis of conduct problems, as assessed using the Nisonger Child Behaviour Rating Form ‒ Conduct Problem subscale (NCBRF-CP). This yielded a final mean score that was 8.61 points lower in the risperidone group compared to the placebo group (95% CI -11.49 to -5.74; moderate-quality evidence).We investigated the effect on weight by performing two meta-analyses. We wanted to distinguish between the effects of antipsychotic medication only and the combined effect wit. There is some evidence that in the short term risperidone may reduce aggression and conduct problems in children and youths with disruptive behaviour disorders There is also evidence that this intervention is associated with significant weight gain.For aggression, the difference in scores of 6.49 points on the ABC ‒ Irritability subscale (range 0 to 45) may be clinically significant. It is challenging to interpret the clinical significance of the differential findings on two different ABS subscales as it may be difficult to distinguish between reactive and proactive aggression in clinical practice. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant. Weight gain remains a concern.Caution is required in interpreting the results due to the limitations of current evidence and the small number of high-quality trials. There is a lack of evidence to support the use of quetiapine, ziprasidone or any other atypical antipsychotic for disruptive behaviour disorders in children and youths and no evidence for children under five years of age. It is uncertain to what degree the efficacy found in clinical trials will translate into real-life clinical practice. Given the effectiveness of parent-training interventions in the management of these disorders, and the somewhat equivocal evidence on the efficacy of medication, it is important not to use medication alone. This is consistent with current clinical guidelines.

Topics: Adolescent; Aggression; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Conduct Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Weight Gain

Topics: Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Dyslipidemias; Humans; Hyperglycemia; Quetiapine Fumarate; Risk Assessment; Treatment Outcome; Weight Gain

The aim of this post-hoc analysis was to determine whether early symptom improvement with extended release quetiapine (quetiapine XR) may predict treatment outcome in patients with major depressive disorder. Data were from 6, double-blind, placebo-controlled studies of quetiapine XR (2 fixed-dose and 2 flexible-dose monotherapy and 2 adjunct studies) in adult patients with major depressive disorder. Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity Score (CGI-S) were assessed at baseline, weeks 2, 4, and 6. Hamilton Rating Scale for Depression (HAM-D) was assessed at baseline and week 6. The MADRS improvement at week 2 (15%, 20%, 25%, 30%) was used to predict response and remission, based on MADRS (50% improvement; total score ≤ 12) or HAM-D (50% improvement; total score ≤ 7). The CGI-S improvement (1 point) at week 2 was used to predict final outcome (CGI-S score ≤ 2). The predictive value for early improvement with quetiapine XR was found to be "very strong" (Yule's Q coefficient, a combined measure of sensitivity and specificity) using 30% MADRS improvement as the threshold. This was relatively comparable for response and remission and for fixed-dose, flexible-dose, and adjunct studies. This was also observed for placebo. Exceptions were: adjunct studies (where predictivity was lower for ongoing antidepressant/placebo), and for remission (predictivity for remission appeared lower than for response with placebo). In conclusion, outcome at week 6 with quetiapine XR for a major depressive episode could be predicted by 30% improvement after 2 weeks, a finding that could give doctors confidence to continue treatment and may facilitate adherence in patients.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Humans; Multicenter Studies as Topic; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic

The safety and efficacy of quetiapine for the treatment of insomnia in adults are reviewed.. Quetiapine was developed for the treatment of psychiatric disorders, but its antagonism of histamine H1- and serotonin type 2A receptors has the added effect of causing sedation. As such, quetiapine is widely used off-label as a treatment for insomnia. Due to quetiapine's potential adverse effects, guidelines for the treatment of insomnia have recommended the drug's use only in patients with specific comorbid psychiatric disorders. The use of quetiapine for the treatment of insomnia in the absence of comorbid conditions has been evaluated in only two clinical trials of 31 patients in total, and very few studies have evaluated quetiapine use in patients with insomnia and other comorbidities. No trials have been conducted comparing quetiapine with an active control (e.g., zolpidem); the data that exist compare quetiapine to a placebo or there is no comparison and all patients are treated with quetiapine. Very few studies have evaluated quetiapine's efficacy in the treatment of insomnia using sleep objective testing, another limitation of the available data on quetiapine.. Robust studies evaluating the safety and efficacy of quetiapine for the treatment of insomnia are lacking. Given its limited efficacy data, its adverse-effect profile, and the availability of agents approved by the Food and Drug Administration for the treatment of insomnia, quetiapine's benefit in the treatment of insomnia has not been proven to outweigh potential risks, even in patients with a comorbid labeled indication for quetiapine.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders

We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chemotherapy, Adjuvant; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Synergism; Humans; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Remission Induction; Risperidone; Treatment Outcome; Young Adult

A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Drug Combinations; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lithium Compounds; Lurasidone Hydrochloride; Quetiapine Fumarate; Thiazoles; Valproic Acid

The efficacy of quetiapine XR was investigated in patients with major depressive disorder and differing levels of baseline severity. Pooled data from four placebo-controlled monotherapy studies of quetiapine XR (50-300 mg/day) were analyzed. Post-hoc analyses were carried out to assess change from baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) total score at endpoint (week 6 or 8) to week 1, and response (≥50% reduction in MADRS total score) and remission (MADRS total score≤10) rates at endpoint for all patients and six baseline severity cohorts (MADRS total score ≥24, ≥26, ≥28, ≥30, ≥32, and ≥34). In total, 1752 patients (all patients) were evaluated (MADRS score at baseline: ≥24, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; and ≥34, n=500). At endpoint, quetiapine XR reduced MADRS total score in all patients (P<0.001) and each severity cohort (≥24, ≥26, ≥28, ≥30, and ≥32, P<0.001; ≥34, P<0.01) versus placebo. Quetiapine XR also improved MADRS total score at week 1, response rates for each severity cohort, and remission rates in five out of six severity cohorts, versus placebo. Quetiapine XR monotherapy showed antidepressant effects in patients with major depressive disorder across different levels of baseline severity.

Topics: Cohort Studies; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

Clinical trials are not generally powered to analyze outcomes such as sustained response. We evaluated sustained response rates for patients with major depressive disorder receiving quetiapine XR as monotherapy or adjunct therapy.. Post hoc analyses of pooled data from four previously reported randomized, placebo-controlled studies of quetiapine XR 150 and 300 mg/day as monotherapy or adjunct therapy to ongoing antidepressant. Sustained response rates (≥50% reduction in MADRS total score at specific timepoint and each subsequent visit until Week 6) were calculated at Weeks 1, 2, and 4; rates were compared using a Cochran-Mantel-Haenszel analysis.. In the monotherapy studies, the proportion of patients experiencing sustained response was greater with quetiapine XR 150 mg/day versus placebo at Week 2 (20.0% vs. 13.3%; p<0.05) and Week 4 (33.3% vs. 23.3%; p<0.01) (observed cases [OC]). The corresponding sustained response rates for quetiapine XR 300 mg/day were 18.0% (p=0.104) and 29.7% (p=0.063), respectively (OC). The proportion of patients experiencing sustained response was greater in the adjunct studies versus placebo at Weeks 2 and 4 for quetiapine XR 150 (Week 2, 30.1% vs. 15.2%, p<0.001; Week 4, 40.1% vs. 32.0%, p<0.05) and 300 mg/day (Week 2, 29.0% vs. 15.2%, p<0.001; Week 4, 42.0% vs. 32.0%, p<0.05) (OC).. Post hoc analyses, acute treatment period; no active comparator.. Quetiapine XR as monotherapy (150 mg/day at Weeks 2 and 4) or adjunct to ongoing antidepressant therapy (150 and 300 mg/day at Weeks 2 and 4) increased sustained response rates versus placebo.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Young Adult

Approximately half of the patients with major depressive disorder (MDD) respond insufficiently to current antidepressants, resulting in increased risk of relapse and residual symptoms. Strategies available include dose increase, combination with a second agent, switching antidepressants, adjunct treatment, psychotherapy or exercise. Efficacy and tolerability of once-daily extended-release quetiapine fumarate (quetiapine XR) adjunct to index antidepressant therapy in patients with MDD and an inadequate response to treatment were assessed in two acute studies as part of a global clinical trial program. Quetiapine XR significantly improved depressive symptoms versus placebo. Significant improvement in quality of life versus placebo was confined to elderly patients with MDD. Tolerability was consistent with the known pharmacological profile of quetiapine: the most common adverse events were dry mouth, somnolence, sedation, dizziness and fatigue. Quetiapine XR is approved in the EU, USA and several other countries worldwide as adjunctive treatment for patients with MDD and an inadequate response to previous antidepressants.

Topics: Antidepressive Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Drug Administration Schedule; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

Pharmacotherapy, psychotherapy and other nonpharmacological interventions are used in patients with major depressive disorder (MDD). However, 50% of the patients with MDD fail to achieve a response to first-line antidepressant treatment. In four of five acute monotherapy studies, once-daily extended-release quetiapine fumarate (quetiapine XR) significantly improved depressive symptoms compared with placebo in patients with MDD. One acute monotherapy study demonstrated that neither quetiapine XR nor escitalopram had a statistically significant separation from placebo on the primary endpoint. Quetiapine XR maintenance therapy also significantly reduced the risk of recurrence of a depressive event. No significant improvement in overall quality of life was observed versus placebo except in the acute elderly study. Tolerability findings were consistent with the known pharmacological profile of quetiapine; the most common adverse events were dry mouth, sedation, somnolence and dizziness. Quetiapine XR monotherapy has been approved as a treatment for MDD in a limited number of countries.

Topics: Antidepressive Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Drug Administration Schedule; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

Prospectively planned pooled analysis evaluating the efficacy of quetiapine extended release (XR) monotherapy in major depressive disorder (MDD). Data were pooled from two 6-week, randomized, double-blind, placebo-controlled studies of quetiapine XR in outpatients with MDD. The primary endpoint was Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from randomization at week 6. Other evaluations were MADRS response/remission, Hamilton Rating Scale for Anxiety, and subgroup analyses. A total of 968 patients were randomized to quetiapine XR, 150 mg/day (n=315), 300 mg/day (n=323), or placebo (n=330). The mean MADRS total score reductions from randomization were significant at week 6 with quetiapine XR, 150 mg/day (-14.7; P<0.001) and 300 mg/day (-14.7; P<0.001) versus placebo (-11.1), with significant reductions versus placebo from week 1 onward. Response rates (week 6): 52.7% (P<0.001) quetiapine XR 150 mg/day and 49.5% (P<0.001) quetiapine XR 300 mg/day versus placebo (33.0%). MADRS remission (score≤8; week 6): 23.5% (P=0.208) quetiapine XR 150 mg/day and 28.8% (P<0.01) quetiapine XR 300 mg/day versus placebo (19.4%). Quetiapine XR (both doses) significantly improved eight of 10 MADRS items versus placebo at week 6. The therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as sex, age, or severity of depression. In patients with MDD, quetiapine XR (150 and 300 mg/day) monotherapy reduced depressive symptoms, with significant improvements compared with placebo from week 1 onward.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Humans; Logistic Models; Male; Middle Aged; Multicenter Studies as Topic; Placebos; Predictive Value of Tests; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; United States; Young Adult

Disruptive behaviour disorders include conduct disorder, oppositional defiant disorder and disruptive behaviour not otherwise specified. Attention deficit hyperactivity disorder (ADHD) is frequently associated with disruptive behaviour disorders. The difficulties associated with disruptive behaviour disorders are demonstrated through aggression and severe behavioural problems. These often result in presentation to psychiatric services and may be treated with medications such as atypical antipsychotics. There is increasing evidence of a significant rise in the use of atypical antipsychotics for treating disruptive behaviour disorders in child and adolescent populations.. To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths. . We searched the following databases in August 2011: CENTRAL (2011, Issue 3), MEDLINE (1948 to August Week 1), EMBASE (1980 to 2011 Week 32), PsycINFO (1806 to August Week 2 2011), CINAHL (1937 to current), ClinicalTrials.gov (searched 15 August 2011), Australian New Zealand Clinical Trials Registry (ANZCTR) (searched 15 August 2011), CenterWatch (searched 15 August 2011) and ICTRP (searched 15 August 2011).. We included randomised controlled trials with children and youths up to and including the age of 18, in any setting, with a diagnosis of a disruptive behaviour disorder. We included trials where participants had a comorbid diagnosis of attention deficit hyperactivity disorder, major depression or an anxiety disorder.. Two review authors independently selected the studies and disagreements were resolved by discussion. Two review authors extracted data independently. One review author entered data into Review Manager software and another checked it. We contacted trial authors for information about adverse effects and to provide missing data.. We included eight randomised controlled trials, spanning 2000 to 2008. Seven assessed risperidone and one assessed quetiapine. Three of the studies were multicentre. Seven trials assessed acute efficacy and one assessed time to symptom recurrence over a six-month maintenance period.We performed meta-analyses for the primary outcomes of aggression, conduct problems and weight changes but these were limited by the available data as different trials reported either mean change scores (average difference) or final/post-intervention raw scores and used different outcome measures. We also evaluated each individual trial's treatment effect size where possible, using Hedges' g.For aggression, we conducted two meta-analyses. The first included three trials (combined n = 238) using mean difference (MD) on the Aberrant Behaviour Checklist (ABC) Irritability subscale. Results yielded a final mean score with treatment that was 6.49 points lower than the post-intervention mean score with placebo (95% confidence interval (CI) -8.79 to -4.19). The second meta-analysis on aggression included two trials (combined n = 57) that employed two different outcome measures (Overt Aggression Scale (modified) (OAS-M) and OAS, respectively) and thus we used a standardised mean difference. Results yielded an effect estimate of -0.18 (95% CI -0.70 to 0.34), which was statistically non-significant.We also performed two meta-analyses for conduct problems. The first included two trials (combined n = 225), both of which employed the Nisonger Child Behaviour Rating Form - Conduct Problem subscale (NCBRF-CP). The results yielded a final mean score with treatment that was 8.61 points lower than that with placebo (95% CI -11.49 to -5.74). The second meta-analysis on conduct problems included two trials (combined n = 36), which used the Conners' Parent Rating Scale - Conduct Problem subscale (CPRS-CP). Results yielded a mean score with treatment of 12.67 lower than with placebo (95% CI -37.45 to 12.11), which was a statistically non-significant result.With respect to the side effect of weight gain, a meta-analysis of two studies (combined n = 138) showed that participants on risperidone gained on average 2.37 kilograms more than those in the placebo group over the treatment period (MD 2.37; 95% CI 0.26 to 4.49).For individual trials, there was a range of effect sizes (ranging from small to large) for risperidone reducing aggression and conduct problems. The precision of the estimate of the effe. There is some limited evidence of efficacy of risperidone reducing aggression and conduct problems in children aged 5 to 18 with disruptive behaviour disorders in the short term.For aggression, the difference in scores of 6.49 points on the ABC Irritability subscale (range 0 to 45) may be clinically significant. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant.Caution is required due to the limitations of the evidence and the small number of relevant high-quality studies. The findings from the one study assessing impact in the longer term suggest that the effects are maintained to some extent (small effect size) for up to six months. Inadequately powered studies produced non-significant results. The evidence is restricted by heterogeneity of the population (including below average and borderline IQ), and methodological issues in some studies, such as use of enriched designs and risk of selection bias. No study addressed the issue of pre-existing/concurrent psychosocial interventions, and comorbid stimulant medication and its dosage was only partially addressed. There is currently no evidence to support the use of quetiapine for disruptive behaviour disorders in children and adolescents.It is uncertain to what degree the efficacy found in clinical trials will translate into real life clinical practice. Participants in the studies were recruited from clinical services but those who agree to take part in the clinical trials are a subset of the overall population presenting for care. There are no research data for children under five years of age. Further high-quality research is required with large samples of clinically representative youths and long-term follow-up to replicate current findings.

Topics: Adolescent; Aggression; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Conduct Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Weight Gain

Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect.. This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012.. MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. STUDY ELIGIBLE CRITERIA, PARTICIPANTS AND INTERVENTIONS: Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied.. All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model.. A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) of the quetiapine-treated group were higher than those of the placebo-treated group with the WMDs (95%CI) of -3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. All studies defined the response and remission as ≥ 50% reduction of the MADRS total score and the MADRS total score of ≤8 at endpoint, respectively. The overall response and remission rates were significantly greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled discontinuation rate was not significantly different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). With respect to sleep time, the pooled mean change Pittsburgh Sleep Quality Index (PSQI) scores of the quetiapine-treated group was also significantly higher than that of the placebo-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)].. Variety of quetiapine XR doses and the small number of RCTs were key limitations of this meta-analysis.. Based on the limited evidence obtained from three RCTs, quetiapine XR is effective for adult patients with MDD. The high dropout rate due to adverse events suggests that some MDD patients may not be able to tolerate quetiapine XR. Due to the balance of its efficacy benefit and risk of side effects, as the overall discontinuation rate shown, the acceptability of this agent is not more than placebo. These results should be viewed as the very preliminary one. Further studies in this area are warranted. IMPLICATION OF KEY FINDINGS: Quetiapine may be an alternative antidepressant. However, both risk and benefit of this agent should be taken into account for an individual patient with MDD.

Topics: Acute Disease; Adolescent; Adult; Aged; Antidepressive Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Remission Induction

Topics: Affective Symptoms; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia

Quetiapine extended-release (quetiapine-XR) has been studied in patients with schizophrenia, bipolar mania, bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The purpose of this study was to compare the tolerability and sensitivity of quetiapine-XR among these psychiatric conditions. The discontinuation due to adverse events (DAEs) and reported somnolence in randomized, double-blind, placebo-controlled studies of quetiapine-XR in these psychiatric conditions were examined. The absolute risk reduction or increase and the number needed to treat to benefit (NNTB) or harm (NNTH) for DAEs and reported somnolence of quetiapine-XR ≥ 300 mg/d relative to placebo were estimated. Data from one study in schizophrenia (n=465), one in mania (n=316), one in bipolar depression (n=280), two in refractory MDD (n=624), two in MDD (n=669) and three in GAD (n=1109) were available. The risk for DAEs of quetiapine-XR relative to placebo was significantly increased in bipolar depression (NNTH=9), refractory MDD (NNTH=8), MDD (NNTH=9), and GAD (NNTH=5), but not in schizophrenia and mania. The risk for reported somnolence of quetiapine-XR relative to placebo was significantly increased in schizophrenia (600 mg/d NNTH=15 and 800 mg/d NNTH=11), mania (NNTH=8), bipolar depression (NNTH=4), refractory MDD (NNTH=5), MDD (NNTH=5) and GAD (NNTH=5). These results suggest that patients with GAD had the poorest tolerability during treatment with quetiapine-XR, but they had a similar sensitivity as those with bipolar depression and MDD. Patients with schizophrenia or mania had a higher tolerability and a lower sensitivity than those with bipolar depression, MDD, or GAD.

Topics: Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Mental Disorders; Placebos; Quetiapine Fumarate; Risk; Schizophrenia; Treatment Outcome

The aim of this systematic review was to examine the efficacy and safety of second-generation antipsychotics (SGAs) in nonpsychotic major depressive disorder (MDD).. In MDD, SGA monotherapy or adjunctive therapy to conventional antidepressants showed rapid onset of antidepressant efficacy. Although maintenance data are limited, quetiapine monotherapy, risperidone adjunctive therapy, and amisulpride adjunctive therapy significantly delayed the time to relapse as compared with placebo. In general, extrapyramidal symptoms appeared to be low with SGAs, but a higher incidence of akathisia was observed with aripiprazole. An elevated risk of weight gain was observed with olanzapine-fluoxetine combination, risperidone, aripiprazole, and quetiapine compared with placebo. At present, there are insufficient data to confidently distinguish between different SGAs in the treatment of MDD. A recent meta-analysis found that adjunctive SGAs were significantly more effective than placebo, but differences in efficacy were not identified among the studied agents, nor were outcomes affected by trial duration or the method of establishing treatment resistance.. Both SGA monotherapy and adjunctive therapy showed greater efficacy in the treatment of MDD than placebo, but augmentation is more widely utilized in treatment-resistant depression. Clinicians should routinely monitor for cardiometabolic side-effects and extrapyramidal symptoms during SGA therapy.

Topics: Adult; Amisulpride; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Sulpiride

Quetiapine extended release (XR) is a once-daily oral formulation of the atypical antipsychotic quetiapine that is available for use as adjunctive therapy in major depressive disorder (MDD). Systemic quetiapine exposure after orally administered quetiapine XR is similar to that of quetiapine immediate release at the same dosage, although quetiapine XR is absorbed more slowly and plasma concentrations are more stable over time. In two 6-week, randomized, double-blind, placebo-controlled, multinational trials in patients with MDD with an inadequate response to antidepressants, quetiapine XR 300 mg/day adjunctive to antidepressant reduced depressive symptoms significantly more than antidepressant plus placebo, according to changes in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores. In one trial, adjunctive quetiapine XR 150 mg/day also led to significantly greater reductions in MADRS total scores than antidepressant plus placebo. MDD response rates were significantly higher with adjunctive quetiapine XR 300 mg/day (but not 150 mg/day) than with antidepressant plus placebo. The numbers needed to treat to achieve an additional response over antidepressant plus placebo were 11-18 and 8-9 in the quetiapine XR 150 and 300 mg/day dosage groups, respectively. Treatment-emergent adverse events were mostly of mild to moderate severity; 1% of adjunctive quetiapine XR and 1.3% of antidepressant plus placebo recipients reported serious adverse events.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Chemotherapy, Adjuvant; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Quetiapine fumarate extended release (XR) has been approved for treatment of schizophrenia and bipolar disorder. Quetiapine may have antidepressant effects through effects on 5-HT(2A) receptor, 5-HT(1A) receptor, dopamine receptor, glutamate receptor and norepinephrine transporter. Recently, 7 large-scale randomized, double-blind, placebo (2-studies with active comparator)-controlled clinical trials have demonstrated that quetiapine XR has clinically meaningful efficacy as monotherapy and adjunct therapy to antidepressants for the treatment of adult patients with major depressive disorder (MDD). In such clinical trials, quetiapine XR was generally well tolerated, although weight gain and changes in metabolic parameters, consistent with the known profile of quetiapine, were observed in some patients. As of December 2009, the United States Food and Drug Administration has approved quetiapine XR for the adjunct treatment of MDD. From the data of currently available clinical trials, this review provides an overview of the data and clinical implications for quetiapine XR in the treatment of MDD to enhance clinicians understanding of the use of quetiapine XR in the treatment of MDD.

Topics: Antidepressive Agents; Antipsychotic Agents; Clinical Trials as Topic; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Delivery Systems; Humans; Quetiapine Fumarate; Time Factors; Treatment Outcome

To describe the efficacy and safety of adjunctive aripiprazole, olanzapine, and quetiapine for major depressive disorder.. Published registration study reports, supplemented by clinical trial synopses as disclosed by manufacturers and product labeling.. All available reports of studies were identified.. Descriptions of the principal results and calculation of number needed to treat (NNT) for response and remission and number needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated.. Three registration studies of adjunctive aripiprazole, 5 for olanzapine-fluoxetine combination, and 2 for quetiapine extended-release reveal NNT for response and remission to range from 7 to 14 and 7 to 13, respectively, for adjunctive antipsychotic versus antidepressant monotherapy, depending on the antipsychotic and/or dose. Adverse event profiles for the 3 different adjunctive antipsychotics are more diverse, with adjunctive aripiprazole more strongly associated with akathisia (NNH, 6), adjunctive olanzapine with weight gain (NNH, 3), and adjunctive quetiapine with somnolence (NNH, 5 for 300 mg/d and NNH, 6 for 150 mg/d).. Number needed to treat and NNH can be used to quantify efficacy and tolerability outcomes and help place various therapeutic options into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and the patient the trade-offs between obtaining potential benefits versus harms. In the case of the adjunctive second-generation antipsychotics approved for treating major depressive disorder, these trade-offs vary greatly among the choices available and require careful, individualized, patient-centered clinical decision making.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Biostatistics; Clinical Trials as Topic; Depressive Disorder, Major; Dibenzothiazepines; Drug Combinations; Drug Therapy, Combination; Epidemiologic Measurements; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones

Two positive studies evaluated adjunctive extended release quetiapine fumarate (quetiapine XR) in patients with major depressive disorder (MDD) showing inadequate response to antidepressant treatment. This preplanned, pooled analysis provides an opportunity for subgroup analyses investigating the influence of demographic and disease-related factors on observed responses. Additional post hoc analyses examined the efficacy of quetiapine XR against specific depressive symptoms including sleep.. Data were analysed from two 6-week, multicentre, double-blind, randomised, placebo-controlled studies, prospectively designed to be pooled. Patients received once-daily quetiapineXR 150mg/day (n=309), 300mg/day (n=307) or placebo (n=303) adjunctive to ongoing antidepressant therapy. The primary endpoint was change from randomisation to Week 6 in MADRS total score. Other assessments included MADRS response (≥50% decrease in total score) and remission (total score≤8), change from randomisation in HAM-D, HAM-A, PSQI global and CGI-S scores.. Quetiapine XR (150 and 300mg/day) reduced MADRS total scores vs placebo at every assessment including Week 6 (-14.5, -14.8, -12.0; p<0.001 each dose) and Week 1 (-7.8,-7.3,-5.1; p<0.001 each dose). For quetiapineXR 150 and 300mg/day and placebo, respectively at Week 6: MADRS response 53.7% (p=0.063), 58.3% (p<0.01) and 46.2%; MADRS remission 35.6% (p<0.01), 36.5% (p<0.001) and 24.1%. QuetiapineXR 150 and 300mg/day significantly improved HAM-D, HAM-A, PSQI and CGI-S scores at Week 6 vs placebo. Quetiapine XR demonstrated broad efficacy, independent of factors including concomitant antidepressant.. Fixed dosing; lack of active comparator.. Adjunctive quetiapine XR is effective in patients with MDD and an inadequate response to antidepressant therapy, with improvement in depressive symptoms seen as early as Week 1.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Humans; Middle Aged; Multicenter Studies as Topic; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Young Adult

Major depressive disorder (MDD) is a common condition with a lifetime prevalence of 15% to 18%, which leads to considerable suffering and disability. Some antipsychotics have been reported to induce remission in major depression, when added to an antidepressant.. To evaluate the effects of second-generation antipsychotic (SGA) drugs (alone or augmentation) compared with placebo or antidepressants for people with MDD or dysthymia.. The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched up to 21 July 2010. The author team ran complementary searches on clinicaltrials.gov and contacted key authors and drug companies.. We included all randomised, double-blind trials comparing oral SGA treatment (alone or augmentation) with other forms of pharmaceutical treatment or placebo in people with MDD or dysthymia.. We extracted data independently. For dichotomous data we calculated the odds ratio (OR) and 95% confidence interval (CI) on an intention-to-treat basis, and for continuous data the mean difference (MD), based on a random-effects model. We presented each comparison separately; we did not perform a pooled data analysis.. We included 28 trials with 8487 participants on five SGAs: amisulpride, aripiprazole, olanzapine, quetiapine and risperidone.Three studies (1092 participants) provided data on aripiprazole augmentation in MDD. All efficacy data (response n = 1092, three RCTs, OR 0.48; 95% CI 0.37 to 0.63), (MADRS n = 1077, three RCTs, MD -3.04; 95% CI -4.09 to -2) indicated a benefit for aripiprazole but  more side effects (weight gain, EPS) .Seven trials (1754 participants) reported data on olanzapine. Compared to placebo fewer people discontinued treatment due to inefficacy; compared to antidepressants there were no efficacy differences, olanzapine augmentation showed symptom reduction (MADRS n = 808, five RCTs, MD -2.84; 95% CI -5.48 to -0.20), but also more weight or prolactin increase.Quetiapine data are based on seven trials (3414 participants). Compared to placebo, quetiapine monotherapy (response n = 1342, three RCTs, OR 0.52; 95% CI 0.41 to 0.66) and quetiapine augmentation (response n = 937, two RCTs, OR 0.68; 95% CI 0.52 to 0.90) showed symptom reduction, but quetiapine induced more sedation.Four trials (637 participants) presented data on risperidone augmentation, response data were better for risperidone (n = 371, two RCTs, OR 0.57; 95% CI 0.36 to 0.89) but augmentation showed more prolactin increase and weight gain.Five studies (1313 participants) presented data on amisulpride treatment for dysthymia. There were some beneficial effects compared to placebo or antidepressants but tolerability was worse.. Quetiapine was more effective than placebo treatment. Aripiprazole and quetiapine and partly also olanzapine and risperidone augmentation showed beneficial effects compared to placebo. Some evidence indicated beneficial effects of low-dose amisulpride for dysthymic people. Most SGAs showed worse tolerability.

Topics: Amisulpride; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Dysthymic Disorder; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Sulpiride

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate

Results from pivotal registration trials in major depressive disorder cohere with outcomes from effectiveness studies indicating that the majority of individuals receiving single-agent pharmacotherapy fail to achieve and sustain symptomatic remission. Several factors provided the impetus for this review: suboptimal efficacy with existing pharmacotherapy for major depressive disorder, quetiapine XR efficacy in the acute and maintenance treatment of bipolar depression, emerging pharmacodynamic evidence that quetiapine XR (and/or its metabolites) uniquely engages monoaminergic systems salient to symptom relief in depressive syndromes, the increasing use of second-generation antipsychotics in the treatment of major depressive disorder and the recent FDA review of quetiapine XR in major depressive disorder. Studies reviewed herein are pivotal registration trials that evaluated the acute and maintenance efficacy and tolerability of quetiapine XR (as monotherapy and as adjunctive treatment) in major depressive disorder. In addition, we also review recent investigations characterizing the pharmacodynamic effect of quetiapine's principal active metabolite, norquetiapine. All studies were obtained from AstraZeneca (Wilmington, DE, USA) and have been presented at national/international scientific meetings. Taken together, extant studies demonstrated that quetiapine XR (50 - 300 mg) provides rapid and sustained symptomatic improvement in the acute and maintenance treatment of major depressive disorder. Quetiapine XR may also offer advantages relative to duloxetine in time to onset of antidepressant action. The major limitations of quetiapine XR use in major depressive disorder relate to weight gain and disrupted glucose/lipid homeostasis as well as sedation/somnolence. Quetiapine XR has tolerability advantages compared with duloxetine on measures of sexual dysfunction. The data from the studies reviewed herein also indicate that quetiapine XR poses a low risk for extrapyramidal side effects in middle-aged and elderly individuals with major depressive disorder.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Chronic Disease; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment-resistant depression (TRD). This paper will review a biochemical rationale and will summarize the data regarding the effectiveness of AAPs in TRD.. Studies were identified using searches of Pubmed/Medline, EMBase and the Cochrane databases by cross-referencing the term 'depression' with each of the six AAPs.. After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia.. The existing research provides some support for the beneficial effects of AAPs when combined with SSRI's in TRD. These medications pose significant risks that must be considered in their use.

Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Drug Resistance; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Serotonin 5-HT2 Receptor Antagonists; Thiazoles; Trazodone; Triazoles

Studies have found that a large percentage of depressed patients may have limited response and remission rates when treated with traditional antidepressants. Options for augmenting antidepressant treatment include buspirone, lithium, and triiodothyronine. There are also increasing data concerning the use of atypical antipsychotics as augmenting agents in the treatment of unipolar, nonpsychotic, treatment-resistant depression. Aripiprazole has recently received an indication from the U.S. Food and Drug Administration (FDA) for adjunctive treatment in unipolar, nonpsychotic depression, the first indication of its kind, after two double-blind trials; doses were slightly lower than those recommended for monotherapy in schizophrenia or bipolar disorder. Olanzapine and risperidone have several controlled clinical trials indicating the efficacy of both of these agents, generally at low doses. One trial of quetiapine suggested that it may not be effective in the treatment of unipolar, nonpsychotic depression. One open-label trial of ziprasidone indicated some efficacy. According to these results, aripiprazole, olanzapine, and risperidone are reasonable choices as augmentation agents, with only aripiprazole currently having an FDA indication for this use. Given the preliminary results, double-blind, placebo-controlled trials with quetiapine and ziprasidone are needed, as well as studies comparing atypical antipsychotic agents with traditional augmentation agents in the treatment of depression.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Drug Synergism; Drug Therapy, Combination; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

The metric of number needed to treat (NNT), defined as the number of patients who need to be treated to achieve one additional favorable outcome, can help clinicians appraise claims that one intervention is meaningfully superior to the other.. A review of the use of NNT to evaluate the differences between interventions in the treatment of depression, schizophrenia and bipolar disorder. Instead of using disparate measures such as point change on a rating scale, kilograms gained over time or relative differences, results can be converted into a common unit of measure -'patient units'- so that the clinician can anticipate how often actual differences between interventions would be expected to be observed. Calculation of NNT is demonstrated using reports published in the psychiatric literature, together with different graphical techniques to display this.. Clinical trial results expressed as NNT can be easily summarized and communicated effectively to patients, their families and payers. Limitations include ensuring that the NNT metric is calculated from well-designed and well-conducted research that enrolls subjects similar to patients that one treats in actual clinical practice, with doses of medications similar to what is used in the 'real world'. Direct calculation of NNT is limited to binary or dichotomous outcomes.. Using NNT can help predict treatment response in terms of both efficacy and tolerability.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Data Interpretation, Statistical; Depressive Disorder, Major; Dibenzothiazepines; Duloxetine Hydrochloride; Evidence-Based Medicine; Humans; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Secondary Prevention; Thiophenes; Treatment Outcome

Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.. We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.. In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.. Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Lamotrigine; Olanzapine; Prevalence; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Outcome; Triazines

Antidepressant medications have eased the suffering of millions of people. In addition to treating depression, antidepressant drugs also treat several anxiety disorders. Unfortunately, there are problematic limitations with antidepressant agents, including a delayed therapeutic response and insufficient efficacy. Emerging evidence shows that atypical antipsychotic agents can be used as augmentation therapy in patients with poor responses to antidepressants. Future drugs combining key features of antidepressant and atypical antipsychotic agents could offer new promise for patients suffering from obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, generalized anxiety disorder and depression.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Depressive Disorder, Major; Dibenzothiazepines; Drug Design; Drug Synergism; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Olanzapine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Histamine; Receptors, Serotonin; Risperidone; Stress Disorders, Post-Traumatic

Cumulative data indicate that atypical antipsychotics can serve as adjunctive as well as alternative agents in the treatment of drug-resistant mood disorders. Olanzapine and risperidone add-on treatment was found to be effective for major depression with psychotic features and good results were achieved with currently available atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine and ziprasidone) in reducing symptoms of acute mania, especially when added to mood stabilizers. The role of atypical antipsychotics in maintenance and prophylactic treatment is not yet clear. Although there are differences in the side effect profiles of the various atypical antipsychotics, their use is limited by adverse effects such as extrapyramidal symptoms, weight gain, somnolence and sexual dysfunction.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Quality of Life; Quetiapine Fumarate; Treatment Outcome

To assess the efficacy, safety, and tolerability of brexpiprazole as adjunctive treatment in adults with major depressive disorder (MDD) and an inadequate response to prior antidepressant treatment (ADT).. Patients with a current major depressive episode after prior treatment with 1-3 ADTs entered an 8- or 10-week prospective treatment phase in which they received double-blind placebo adjunct to open-label ADT. Inadequate responders were randomized (2:2:1) to brexpiprazole 2-3 mg/day, placebo, or quetiapine extended-release (XR) 150-300 mg/day, adjunct to the same ADT, for 6 weeks. The primary efficacy endpoint was the change from baseline (randomization) to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The key secondary efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score.. Adjunctive brexpiprazole showed a greater improvement in MADRS total score than adjunctive placebo (least squares mean difference [95% confidence interval] = -1.48 [-2.56, -0.39]; p = .0078), whereas adjunctive quetiapine XR did not separate from placebo (-0.30 [-1.63, 1.04]; p = .66). Adjunctive brexpiprazole failed to separate from placebo on the SDS mean score (-0.23 [-0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items (family life and social life). The most frequent treatment-emergent adverse events in patients receiving brexpiprazole were akathisia (6.1%), somnolence (5.6%), and headache (5.6%).. Adjunctive brexpiprazole 2-3 mg/day improved symptoms of depression compared with adjunctive placebo in patients with MDD and an inadequate response to ADTs, and was well tolerated with no unexpected side effects.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Headache; Humans; Male; Middle Aged; Prospective Studies; Psychomotor Agitation; Quetiapine Fumarate; Quinolones; Thiophenes; 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

Genotype and drug pharmacology may contribute to variations in brain response to antidepressants. We examined the impact of two antidepressants with differential actions on serotonin transporter and the 5-HHTLPR-S/Lg polymorphisms on amygdala responses in major depressive disorder (MDD).. Caucasians with MDD were given either citalopram or quetiapine extended release for 8 weeks. Patients were genotyped for 5-HTTLPR. Clinical efficacy was assessed using the Hamilton Depression Rating Scale. fMRI responses to negative emotional faces were acquired at baseline, week 1 and week 8. The outcome measure was change in amygdala responses at week 8.. Citalopram had no effect on amygdala responses in MDD patients with S/Lg alleles at weeks 1 and 8 compared with baseline, whereas it induced changes in amygdala responses in LL homozygotes. By contrast, quetiapine decreased amygdala responses at both time points in S/Lg carriers, and changes in amygdala responses at week 8 correlated with a reduction in depression scores. The small number of LL homozygotes in quetiapine group was a limitation. Efficacy of both treatments was comparable.. These preliminary data suggest that pharmacological mechanisms and genetics need to be considered in the development of neuroimaging markers for the evaluation of antidepressant treatments.

Topics: Adult; Aged; Amygdala; Citalopram; Delayed-Action Preparations; Depressive Disorder, Major; Double-Blind Method; Female; Genotyping Techniques; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Polymorphism, Genetic; Quetiapine Fumarate; Serotonin Plasma Membrane Transport Proteins; Treatment Outcome; White People; Young Adult

Identification of predictors of treatment response in patients with major depressive disorder (MDD) may facilitate improved disease management. Data were pooled from two 6-week, double-blind, placebo-controlled studies of extended-release quetiapine (quetiapine XR; 150 or 300 mg/day) as adjunct to ongoing antidepressant therapy. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy outcomes (Week 6 Montgomery Åsberg Depression Rating Scale [MADRS] total score reduction) were evaluated in population subgroups (quetiapine XR both doses pooled, n = 616; placebo, n = 303). Baseline Clinical Global Impressions-Severity (CGI-S) score and previous depressive episodes on Week 6 MADRS total score change, and baseline MADRS individual item scores on Week 6 change in CGI-Improvement score, were also evaluated. No major differences between responders and non-responders to quetiapine XR were observed for patient characteristics or demographic and disease characteristics. No suggestion of a predictive association was found between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes. These analyses showed no major differences between responders and non-responders, and no predictive association between the parameters assessed and efficacy outcomes for adjunct quetiapine XR in patients with MDD and an inadequate response to prior antidepressant therapy.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Young Adult

The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E.. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models.. No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone.. The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Depressive Disorder, Major; Double-Blind Method; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

We evaluated sexual functioning from 6 acute, randomized, placebo-controlled studies (6-10 weeks) of once-daily extended release quetiapine fumarate (quetiapine XR) 50, 150, or 300 mg/day as monotherapy (Studies 1-4) or adjunct therapy (Studies 6-7) in major depressive disorder (MDD).. We present a pre-planned, non-inferiority analysis of quetiapine XR monotherapy versus placebo using Changes in Sexual Functioning Questionnaire (CSFQ) total score change (Studies 1-4). Post hoc analyses evaluated CSFQ total and domain scores for fixed-dose monotherapy (Studies 1-2), modified fixed-dose (Studies 3-4), and adjunct therapy studies (Studies 6-7). CSFQ data for active comparators (duloxetine [Study 2], escitalopram [Study 4]) are reported.. Quetiapine XR monotherapy was non-inferior to placebo for sexual functioning (least squares mean [LSM] difference in CSFQ score change versus placebo, 0.16 [95% confidence interval: -0.59, 0.92]); LSM change in CSFQ score: 1.90, quetiapine XR (all doses) and 1.73, placebo. LSM differences versus placebo (95% confidence interval): 0.18 (-1.40, 1.75), duloxetine (Study 2); 0.16 (-1.77, 2.10), escitalopram (Study 4). LSM differences with adjunct quetiapine XR 150 mg/day (0.52; p = 0.338) or 300 mg/day (0.22; p = 0.679) were comparable with placebo plus antidepressants. Post hoc all-patient and gender-specific analyses were comparable for CSFQ total scores versus placebo with quetiapine XR 50, 150, or 300 mg/day, duloxetine, and escitalopram. Discussion Lack of negative effects on sexual functioning in patients with MDD may improve treatment acceptability.. Quetiapine XR (monotherapy or adjunct therapy) had an impact on sexual function that was comparable with placebo.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Male; Middle Aged; Quetiapine Fumarate; Sex Factors; Sexual and Gender Disorders; Surveys and Questionnaires; Time Factors; United States; Young Adult

This pooled analysis evaluated the efficacy of extended-release quetiapine fumarate (quetiapine XR) adjunct to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). Pooled data were analyzed from two 6-week, double-blind, randomized, placebo-controlled trials of adjunct quetiapine XR (150 and 300 mg/day) in patients with MDD and inadequate response to initial antidepressant monotherapy. This post-hoc analysis included evaluation of change from randomization at week 6 in Montgomery Åsberg Depression Rating Scale (MADRS) total scores (primary endpoint), and week 6 MADRS response and remission rates for quetiapine XR as an adjunct to ongoing SSRI or SNRI. In total, 189, 178, and 202 patients received quetiapine XR 150 mg/day+SSRI, 300 mg/day+SSRI, and placebo+SSRI, respectively, whereas 82, 90, and 76 patients, respectively, received quetiapine XR 150 mg/day+SNRI, 300 mg/day+SNRI, and placebo+SNRI. At week 6, quetiapine XR 150 mg/day+SSRI and 300 mg/day+SSRI reduced the MADRS total score from randomization versus placebo+SSRI [least squares mean (LSM) change, -14.70 (P<0.05) -14.72 (P<0.05) vs. -12.59, respectively]. Quetiapine XR 150 mg/day+SNRI (LSM change, -14.68, P<0.01) and 300 mg/day+SNRI (LSM change, -14.99, P<0.01) also reduced the MADRS total score from randomization at week 6 versus placebo+SNRI (-10.77). In conclusion, in patients with MDD and inadequate response to ongoing antidepressant, adjunct quetiapine XR (150 and 300 mg/day) was effective in both SSRI and SNRI subgroups.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Young Adult

This study evaluated extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD) according to baseline levels of anxiety, sleep disturbance, and pain. Post-hoc analyses of data from an 11-week (9-week randomized-treatment, 2-week post-treatment phase), double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) monotherapy in elderly (≥66 years) patients (n=338) with MDD were carried out. Outcomes included randomization to week 9 change in Montgomery Åsberg Depression Rating Scale (MADRS) score and week 9 response (≥50% MADRS score reduction) rates. Post-hoc analyses were carried out to assess subgroups of patients with MDD according to baseline levels in terms of the following: higher or lower anxiety (Hamilton Rating Scale for Anxiety total score≥20 or < 20, respectively); high or low sleep disturbance [Hamilton Rating Scale for Depression sleep disturbance factor (items 4+5+6) score≥5 or <5, respectively]; and pain visual analog scale total score 40 mm or higher or less than 40 mm. At week 9, quetiapine XR reduced the MADRS total score compared with placebo in the higher anxiety (least squares mean change -17.8 vs. -8.5; P<0.001) and lower anxiety (-14.8 vs. -8.8; P<0.001) subgroups. MADRS total score was also reduced with quetiapine XR compared with placebo in the high (-17.6 vs. -8.7; P<0.001) and low (-14.4 vs. -9.2; P<0.001) sleep disturbance subgroups, as well as in the pain visual analog scale subgroups [≥40 mm (-16.6 vs. -8.9; P<0.001) and <40 mm (-15.7 vs. -8.7; P<0.001)]. Quetiapine XR response rates were higher than those of placebo in all subgroups analyzed. In this study, quetiapine XR (50-300 mg/day) monotherapy was shown to be effective against depressive symptoms in elderly patients with MDD, irrespective of baseline levels of anxiety, sleep disturbance, and pain.

Topics: Aged; Antipsychotic Agents; Anxiety; Delayed-Action Preparations; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Pain; Psychiatric Status Rating Scales; Quetiapine Fumarate; Sleep Wake Disorders

In this study, the impact of quetiapine fumarate extended release (QXR) and escitalopram (ESC) on HPA axis activity was investigated in depressed patients in relationship to antidepressant efficacy.. In a randomized, open-label 5-week trial 60 inpatients suffering from major depression (DSM-IV criteria) were treated for 5 weeks with either QXR (300 mg/day) or ESC (10mg/day). The dexamethasone/CRH (DEX/CRH) test was performed before treatment, after 1, and after 5 weeks of treatment. Cortisol (COR) AUC values were used to assess HPA axis function. The Hamilton Depression Rating Scale was used weekly to estimate antidepressant efficacy.. QXR and ESC showed comparable antidepressant effects but strongly differed in their impact on HPA axis activity. In the QXR group, a marked inhibition of COR AUC levels was observed which was most pronounced after one week of treatment but showed a partial re-increase after 5 weeks of treatment. In contrast, ESC transiently stimulated COR AUC values (week 1) whereas COR AUC levels at week 0 and week 5 were comparable. COR improvement at week 1 (defined as COR peak value reduction between DEX/CRH test 1 and 2) was significantly associated with better clinical outcome.. Apparently, different effects on HPA axis activity reflect distinct pharmacoendocrinological properties of psychotropic drugs.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Citalopram; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Quetiapine Fumarate; Treatment Outcome

Fibromyalgia and major depressive disorder (MDD) frequently co-occur. Quetiapine fumarate extended-release (quetiapine XR) has demonstrated efficacy in the treatment of MDD and has been shown to have analgesic properties in patients with depression. The primary objectives of this study were to evaluate the effects of quetiapine XR on depressive and pain symptoms in patients with MDD and comorbid fibromyalgia, and to assess its safety and tolerability.. This was an 8-week, single-center, double-blind, randomized, controlled trial. A total of 120 nonpsychotic adult outpatients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for MDD and whose diagnosis of fibromyalgia was confirmed according to the American College of Rheumatology criteria were enrolled. The primary end point was the mean change from baseline to week 8 on the 17-item Hamilton Depression Rating (HAM-D) scale. Secondary end points included other depression-rating scores, pain scores, fibromyalgia scores, measures of quality of life and global functioning, and adverse events.. The mean change in the HAM-D score from baseline to week 8 was significantly greater in the quetiapine XR group compared with the placebo group (-10.0 versus -5.8; P = 0.001). Improvements in most secondary outcomes were also significantly greater in the quetiapine XR group. Quetiapine XR was generally well tolerated.. This study is the first to demonstrate that measures of depression, pain, and quality of life are significantly improved with quetiapine XR compared with placebo in patients with a dual diagnosis of MDD and fibromyalgia.

Topics: Adult; Antipsychotic Agents; Comorbidity; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain Measurement; Patient Safety; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

To evaluate quetiapine XR in patients with anxious depression, as defined by HAM-A total and HAM-D anxiety/somatisation factor scores.. Post hoc analyses of pooled data from two 6-week, double-blind, randomised, placebo-controlled studies of adjunctive quetiapine XR (150 or 300 mg/day) in patients with MDD and inadequate response to antidepressants. Patients were stratified in a primary analysis using HAM-A (HAM-A total score at baseline ≥ 20 ["high"] or < 20 ["low"]) and a secondary analysis using HAM-D (anxious depression defined as HAM-D anxiety/somatisation factor score ≥ 7). Outcomes included change in MADRS total score.. In patients with high anxiety levels (HAM-A total score ≥ 20), reductions in MADRS total score were -15.20 (P = 0.122) and -15.92 (P < 0.05) for quetiapine XR 150 and 300 mg/day, respectively, vs. placebo (-13.49). In patients with low levels of anxiety (HAM-A total score < 20), both quetiapine XR doses (P < 0.001) improved MADRS total scores vs. placebo. In the secondary analysis, quetiapine XR 150 (P < 0.01) and 300 mg/day (P < 0.001) improved MADRS total score vs. placebo in patients with HAM-D anxiety/somatisation factor score ≥ 7.. Adjunct quetiapine XR demonstrates efficacy in patients with anxious and non-anxious depression, assessed using HAM-A total score, and anxious depression assessed using HAM-D anxiety/somatisation factor score.

Topics: Adult; Antipsychotic Agents; Anxiety; Chemotherapy, Adjuvant; Comorbidity; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

The impact of Hatha yoga as add-on treatment to quetiapine fumarate extended release (QXR) or escitalopram (ESC) in depressed patients on hypothalamic-pituitary-adrenal (HPA) axis activity was assessed.. 60 inpatients suffering from major depressive disorder (MDD) according to DSM-IV were randomized for a 5 week treatment with Yoga or not (control group) and with either QXR (300 mg/day) or ESC (10 mg/day). Serial dexamethasone/corticotropin releasing hormone (DEX/CRH) tests were performed to assess HPA axis function. The Hamilton Depression Rating Scale (21-HAMD) was used weekly.. A more pronounced down regulation of the HPA axis activity due to yoga could not be detected. The stepwise long term cortisol reduction was seen in both medication groups, irrespectively of yoga add-on treatment. In addition, cortisol improvers in week 1 of therapy (reduction in cortisol peak value within the DEX/CRH test) reached significant greater amelioration of depressive symptoms after 5 weeks.. Our results suggest that antidepressant agents down regulate HPA axis function to a greater extent than additional Hatha yoga treatment. Moreover, an early reduction of HPA system hyperactivity after one week of pharmacological treatment seems to raise the possibility of a favorable treatment response.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Area Under Curve; Citalopram; Corticotropin-Releasing Hormone; Depressive Disorder, Major; Dexamethasone; Dibenzothiazepines; Drug Delivery Systems; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Muscle Stretching Exercises; Outcome Assessment, Health Care; Pituitary-Adrenal System; Quetiapine Fumarate; Yoga; Young Adult

The efficacy of quetiapine XR was investigated in patients with major depressive disorder and differing levels of baseline severity. Pooled data from four placebo-controlled monotherapy studies of quetiapine XR (50-300 mg/day) were analyzed. Post-hoc analyses were carried out to assess change from baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) total score at endpoint (week 6 or 8) to week 1, and response (≥50% reduction in MADRS total score) and remission (MADRS total score≤10) rates at endpoint for all patients and six baseline severity cohorts (MADRS total score ≥24, ≥26, ≥28, ≥30, ≥32, and ≥34). In total, 1752 patients (all patients) were evaluated (MADRS score at baseline: ≥24, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; and ≥34, n=500). At endpoint, quetiapine XR reduced MADRS total score in all patients (P<0.001) and each severity cohort (≥24, ≥26, ≥28, ≥30, and ≥32, P<0.001; ≥34, P<0.01) versus placebo. Quetiapine XR also improved MADRS total score at week 1, response rates for each severity cohort, and remission rates in five out of six severity cohorts, versus placebo. Quetiapine XR monotherapy showed antidepressant effects in patients with major depressive disorder across different levels of baseline severity.

Topics: Cohort Studies; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

This study assessed the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD).. An 11-week (9-week randomized; 2-week posttreatment phase), double-blind, placebo-controlled, Phase III study (D1448C00014).. A total of 53 centers in Argentina, Estonia, Finland, Russia, Ukraine, and the United States.. A total of 338 patients (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD, age ≥66 years, Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 [depressed mood] score ≥2) were randomized (mean age: 71.3 years).. Patients were randomized to quetiapine XR (n = 166; flexible-dosing 50-300 mg/day) or placebo (n = 172).. Primary outcome was Montgomery Åsberg Depression Rating Scale (MADRS) total score change from randomization at Week 9.. At Week 9, quetiapine XR (least squares [LS] means: -16.33, standard error [SE]: 0.95; mean change: -16.0, standard deviation [SD]: 9.3) significantly reduced MADRS total score from randomization versus placebo (LS means [SE]: -8.79 [0.94]; mean [SD]: -9.0 [9.9]); significant improvements were also seen at Week 1 (LS means [SE]: -4.65 [0.53] versus -2.56 [0.53], respectively; mean [SD]: -4.3 [5.1] versus -2.4 [3.7], respectively). At Week 9, secondary outcome variables significantly improved with quetiapine XR versus placebo, including MADRS response (≥50% reduction in total score); MADRS remission (total score ≤8); HAM-D total, HAM-A total, HAM-A psychic and somatic cluster, and Clinical Global Impressions-Severity of Illness (CGI-S) total scores; proportion of patients with CGI-Improvement score of 2 or less; Q-LES-Q-SF% maximum total, Pittsburgh Sleep Quality Index global, and pain Visual Analog Scale scores. Common adverse events (>10% patients with quetiapine XR) were somnolence, headache, dry mouth, and dizziness.. In elderly patients with MDD, quetiapine XR monotherapy (50-300 mg/day, flexibly dosed) is effective at improving depressive symptoms, with symptom improvement observed as early as Week 1. Overall tolerability and safety were consistent with the known profile of quetiapine.

Topics: Aged; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Quetiapine Fumarate

Major depressive disorder (MDD) is frequently associated with reduced quality of life (QoL) and sleep disturbance. We investigated the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on QoL and sleep in elderly patients with MDD.. Prospectively planned analysis of patient-reported data from an 11-week (9-week randomized; 2-week post-treatment), double-blind, placebo-controlled, Phase III study. Elderly patients (≥66 years; DSM-IV MDD; Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 score ≥2) were randomized to quetiapine XR (flexible dosing 50-300 mg/day) or placebo.. MADRS total score change from randomization at Week 9. Patient-reported outcomes: Quality of Life, Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) % of maximum total score (Items 1-14), Q-LES-Q-SF Item 15 ('satisfaction with medication'), Q-LES-Q-SF Item 16 ('overall life satisfaction'), and Pittsburgh Sleep Quality Index (PSQI) global score.. In total, 338 patients were randomized (166 quetiapine XR; 172 placebo). At Week 9, quetiapine XR significantly reduced MADRS total score (-16.33; difference: -7.54; 95% CI: -9.23, -5.85; p<0.001) versus placebo (-8.79). Quetiapine XR significantly improved Q-LES-Q-SF % of maximum total score (16.86; difference: 7.69; 95% CI: 4.99, 10.39; p<0.001) versus placebo (9.17), with numerical improvement in Q-LES-Q-SF Item 15 and improvement in Item 16. Improvement in PSQI global score was observed with quetiapine XR (-6.42; difference: -3.52; 95% CI: -4.26, -2.79; p<0.001) versus placebo (-2.89).. Lack of active-comparator arm, flexible-dose design, acute treatment period.. Quetiapine XR monotherapy improved QoL and sleep in elderly patients with MDD.

Topics: Aged; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Quality of Life; Quetiapine Fumarate; Sleep; Sleep Wake Disorders

Sleep disturbance is common in depression and is a risk factor for recurrence and suicide. This analysis evaluated the effects of adjunct extended-release quetiapine fumarate (quetiapine XR) on sleep disturbance and quality in patients with major depressive disorder (MDD) and an inadequate response to on-going antidepressant therapy. Pooled data from two 6-wk, randomized, double-blind, placebo-controlled trials were analysed post hoc. Patients received once-daily quetiapine XR [(150 mg/d), n = 309; (300 mg/d), n = 307] or placebo (n = 303) adjunct to on-going antidepressant therapy. Analyses included: change from randomization in Montgomery-Åsberg Depression Rating Scale (MADRS) Item 4 (reduced sleep) score; Hamilton Rating Scale for Depression (HAMD) Items 4 (insomnia-early), 5 (insomnia-middle) and 6 (insomnia-late) scores; HAMD sleep disturbance factor (Items 4+5+6); Pittsburgh Sleep Quality Index (PSQI) global score. Change in MADRS total score was also evaluated in patients stratified by HAMD sleep disturbance factor score (high ≥ 4 and low < 4) at randomization. At week 6, adjunct quetiapine XR (150 and 300 mg/d) reduced MADRS Item 4, HAMD Items 4, 5 and 6, HAMD sleep disturbance factor and PSQI global scores from randomization vs. placebo (all p < 0.001). In patients with high sleep disturbance, quetiapine XR (both doses) improved depressive symptoms (MADRS total score) vs. placebo from week 1 onwards (p < 0.01). Adjunct quetiapine XR improved sleep disturbance and quality vs. placebo in patients with MDD and an inadequate response to on-going antidepressant treatment, and was effective against depressive symptoms in patients experiencing high sleep disturbance.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Sleep Wake Disorders; Time Factors; Treatment Outcome; Young Adult

Effects of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy on sleep quality and disturbance in patients with major depressive disorder (MDD) were evaluated. Pooled data from four 6- or 8-wk placebo-controlled quetiapine XR (50-300 mg/d) monotherapy studies (D1448C00001; D1448C00002; D1448C00003; D1448C00004) were analysed. Primary efficacy end-point was change from randomization in Montgomery Åsberg Depression Rating Scale (MADRS) score. Post hoc analyses of secondary end-points were conducted for change from randomization in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAMD) items 4 (insomnia-early), 5 (insomnia-middle), 6 (insomnia-late) and sleep disturbance factor (items 4 + 5+6) scores; Pittsburgh Sleep Quality Index (PSQI) global scores. MADRS total score change was also evaluated in patients experiencing high and low baseline sleep disturbance (HAMD sleep disturbance factor scores ⩾4 and < 4, respectively). In total, 1808 patients were randomized to quetiapine XR or placebo across four studies. At last assessment, quetiapine XR reduced MADRS item 4, HAMD items 4, 5 and 6, HAMD sleep disturbance factor score and PSQI global scores from baseline vs. placebo (p < 0.001). For those experiencing high sleep disturbance (n = 865, quetiapine XR; n = 514, placebo), quetiapine XR improved MADRS total score vs. placebo at all visits (p < 0.001). For those with low sleep disturbance (n = 252, quetiapine XR; n = 121, placebo), quetiapine XR improved MADRS total score vs. placebo at weeks 2 (p < 0.001), 4 and 6 (both p < 0.05). In conclusion, quetiapine XR (50-300 mg/d) monotherapy improved symptoms of sleep disturbance vs. placebo in patients with MDD, including those with either high or low baseline sleep disturbance levels.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Delivery Systems; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Sleep Wake Disorders; Time Factors; Treatment Outcome; Young Adult

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

Patients with major depressive disorder (MDD) accompanied by physical symptoms may be less responsive to antidepressant treatment. Quetiapine has been evaluated in the treatment of bipolar depression and has been recently approved as an add-on therapy for unipolar depression. Less is known about the efficacy of combination therapies in patients suffering from MDD with somatic symptoms. The aim of the present study was to evaluate the efficacy of quetiapine as adjunctive therapy to the SSRI citalopram in patients with MDD and somatic complaints.. 41 inpatients with nonpsychotic DSM-IV MDD experiencing significant symptoms of somatic distress as defined by a baseline score on the SCL-90-R somatization subscale greater one standard deviation above adult nonpatient norms were randomly assigned to receive either citalopram 40 mg/day plus placebo (n=20) or citalopram 40 mg/day plus quetiapine, 300 to 600 mg/day (n=21) for 6 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS) score.. Mean changes in HDRS scores from baseline to week 6 using last-observation-carried-forward methods were -12.3±6.2 and -10.7±5.1 in the citalopram-quetiapine and citalopram-placebo group, respectively. Remission rates were significant higher in the citalopram-quetiapine-group (41.1%) than in the citalopram-placebo-group (26.3%), respectively.. Although quetiapine as add-on to citalopram did not separate statistically from placebo on the HDRS score in improving depressive symptoms and somatic symptoms in patients with MDD and prominent somatic complaints, higher remission rates and other second outcome parameters showed advantages for quetiapine. Larger, double-blind, placebo-controlled trials of quetiapine as augmentation therapy in MDD with somatic symptoms are warranted.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Chemotherapy, Adjuvant; Citalopram; Comorbidity; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pilot Projects; Placebos; Psychophysiologic Disorders; Quetiapine Fumarate; Treatment Outcome; Young Adult

Depression during midlife years may lead to significant sleep disturbances and adversely impact quality of life (QOL). In this report, we examined the effects of treatment with quetiapine extended release (XR), 150-300 mg/day, on sleep and QOL in 23 midlife women with major depressive disorder (MDD). Quetiapine XR improved subjective sleep distress, overall sleep parameters, and sleep-related QOL, ultimately leading to significant improvement in menopause-related QOL. While larger, controlled trials are still awaited, these preliminary results are encouraging and suggest that quetiapine XR may be a useful tool in treating symptomatic midlife women with MDD.

Topics: Adult; Antipsychotic Agents; Canada; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Menopause; Middle Aged; Quality of Life; Quetiapine Fumarate; Single-Blind Method; Sleep; Sleep Wake Disorders; Treatment Outcome

A pooled analysis was performed on data from two studies evaluating the efficacy of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy for patients with major depressive disorder. Through these analyses (based on Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) measures), we aim to further evaluate the efficacy of quetiapine XR in depressed patients with high levels of anxiety symptoms.. Secondary analyses were conducted of pooled individual patient data from two 8-week (6-week randomized phase, 2-week drug discontinuation phase), double-blind, placebo-controlled studies of quetiapine XR (50-300 mg/day). Outcomes included change from randomization at Week 6 in Montgomery Åsberg Depression Rating Scale (MADRS) total score for patients with anxious and nonanxious depression.. Of 968 patients included in the analysis, 788 (81.4%) were classified as anxious depressed (defined as HAM-D anxiety/somatization factor score ≥ 7) and 180 (18.6%) were nonanxious. For patients with anxious depression and nonanxious depression, statistically significant differences versus placebo in MADRS total score were recorded for quetiapine XR 150 mg/day (-3.24, P < .001 and -4.82, P < .01, respectively) and 300 mg/day (-3.57, P < .001 and -3.39, P < .05, respectively) at Week 6. In the second analysis using an alternate definition of anxious depression (baseline HAM-A total score ≥ 20), quetiapine XR 150 and 300 mg/day resulted in significant differences versus placebo in MADRS total score reduction in patients with high and lower levels of anxiety. The adverse event (AE) profile was similar irrespective of baseline anxiety levels, although patients with anxious depression reported a somewhat greater incidence of AEs.. Quetiapine XR monotherapy improved symptoms of depression in patients with higher and lower levels of anxiety.

Topics: Adult; Antipsychotic Agents; Anxiety; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome

The aim of this study was to assess patients' functioning and sleep quality during extended-release quetiapine fumarate (quetiapine XR) maintenance treatment. A double-blind, randomized-withdrawal maintenance study of quetiapine XR monotherapy was carried out in patients with major depressive disorder. Following 4-8 weeks of open-label quetiapine XR and 12-18 weeks of open-label quetiapine XR stabilization (50, 150, or 300 mg/day), eligible patients were randomized to quetiapine XR (50, 150, or 300 mg/day) or placebo. Secondary variables of the Sheehan Disability Scale (SDS) and the Pittsburgh Sleep Quality Index (PSQI) were used to assess functioning and sleep quality and are reported here. Quetiapine XR significantly maintained functioning versus placebo. Changes in the least squares means (LSM) from randomization in the SDS total scores were as follows: -0.45, quetiapine XR (P<0.05), versus 0.44, placebo. Quetiapine XR significantly maintained SDS domains 'social life/leisure' (-0.19; P<0.05) and 'family life/home responsibilities' (-0.22; P<0.05) versus placebo (0.13 and 0.10, respectively). Quetiapine XR significantly maintained sleep quality (LSM change in PSQI total scores: 0.06, quetiapine XR vs. 1.35, placebo; P<0.001), with five of seven PSQI components being significant for quetiapine XR versus placebo. In conclusion, quetiapine XR (50-300 mg/day) monotherapy better maintains overall functioning and sleep quality than placebo in patients with major depressive disorder.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Monitoring; Female; Humans; Maintenance Chemotherapy; Male; Middle Aged; Quetiapine Fumarate; Secondary Prevention; Sleep Wake Disorders; Young Adult

Evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) once-daily monotherapy for patients with major depressive disorder (MDD).. In this 10-week, (8-week active treatment phase and 2-week drug-discontinuation/tapering phase), multicenter, parallel-group, placebo-controlled, double-blind, randomized, Phase III study (D1448C00003: Opal), patients initially received quetiapine XR 150 mg/day or placebo. At Week 2, inadequate responders (<20% reduction in MADRS total score) were up-titrated to 300 mg/day quetiapine XR or matching placebo for the final 6 weeks. Primary endpoint: change from randomization to Week 8 in MADRS total score. Secondary endpoints included: MADRS response (≥50% reduction in total score from randomization) and changes from randomization to Week 8 in HAM-D and CGI-S.. 310 patients were randomized. At Week 8, quetiapine XR significantly reduced mean MADRS total score versus placebo (-16.49 vs -13.10, respectively; p<0.01). Mean MADRS score was significantly reduced by quetiapine XR versus placebo at Week 1 (p<0.05). MADRS response rates were significantly greater at Week 8 for quetiapine XR versus placebo (61.9% vs 48.0%, respectively; p<0.05). Significant changes in HAM-D total score and CGI-S were seen at Week 8 for quetiapine XR versus placebo. Withdrawal rates due to AEs were 9.9% and 2.6% for quetiapine XR and placebo, respectively. Common AEs (>10% any group during the randomized phase) for quetiapine XR and placebo, respectively were dry mouth (32.9% and 6.5%), sedation (21.7% and 1.9%), somnolence (20.4% and 5.2%), and headache (10.5% and 10.3%).. The study was not designed to compare quetiapine XR 150 mg/day and 300 mg/day; it was intended to reflect dose titration that might occur in clinical practice.. Quetiapine XR monotherapy is effective in patients with MDD, with symptom improvement seen as early as Week 1, and tolerability results consistent with the known profile of quetiapine.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Headache; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Time Factors; Treatment Outcome; Xerostomia; Young Adult

Data about follow-up after acute pharmacological treatment of psychotic depression are scarce.. A 4 month open follow-up was done, preferentially with same medication as during acute treatment, of patients (n=59) with DSM-IV-TR major depressive disorder with psychotic features, aged 18 to 65 years, who had completed as responders an acute double-blind 7 week trial with imipramine, venlafaxine or venlafaxine plus quetiapine. Main outcome measures were Hamilton Rating Scale for Depression and Clinical Global Impression Scale.. Six patients dropped out during the 4 month follow-up. Almost all patients (86.4%; 51/59) remained responder while remission rate increased from 59.3% (35/59) to 86.8% (46/53), independent of treatment. Relapse rate was low (3.8%; 2/53). Tolerability was good. Weight increased with all treatments.. Limitations were the limited sample size and consequent limited statistical power. The treatment during follow-up was not double-blind.. Continuation treatment with the same medication that was effective in the acute treatment trial, remained effective during the 4 month follow-up in many patients leading to further improvement, and was well tolerated.

Topics: Adult; Affective Disorders, Psychotic; Antidepressive Agents; Antipsychotic Agents; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Imipramine; Long-Term Care; Male; Middle Aged; Netherlands; Quetiapine Fumarate; Treatment Outcome; Venlafaxine Hydrochloride

This study evaluated once-daily extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressant treatment. In this 8-wk (6-wk active treatment/2-wk post-treatment drug-discontinuation/follow-up), multicentre, double-blind, placebo-controlled, Phase III study, 446 patients were randomized to quetiapine XR 150 mg/d, 300 mg/d, or placebo adjunct to ongoing antidepressant treatment. The primary endpoint was the change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. At week 6, MADRS total scores significantly improved with quetiapine XR 300 mg/d vs. placebo (-14.7 vs. -11.7, p<0.01). Quetiapine XR 300 mg/d showed significant improvements vs. placebo for: MADRS total score from week 1 onwards; MADRS response [(> or = 50% total score reduction) 58.9% vs. 46.2%, p<0.05] and remission [(total score < or = 8) 42.5% vs. 24.5%, p<0.01] rates; Hamilton Depression Rating Scale (HAMD) (-13.53 vs. -10.80, p<0.01) and Clinical Global Impression-Severity of illness (CGI-S) change (-1.52 vs. -1.23, p<0.05) at week 6. For quetiapine XR 150 mg/d, improvements were not significantly different vs. placebo, except for MADRS (weeks 1 and 2) and HAMD (week 6) total scores. Withdrawal rates due to adverse events (AEs) were: quetiapine XR 150 mg/d 11.5%, 300 mg/d 19.5%, and placebo 0.7%. The most common AEs (>10%) with quetiapine XR were dry mouth, somnolence, sedation, dizziness, constipation, nausea, insomnia, headache, and fatigue. In this study, quetiapine XR 300 mg/d as adjunctive therapy in patients with MDD with an inadequate response to ongoing antidepressant treatment was effective at week 6. However, the difference from placebo for quetiapine XR 150 mg/d at week 6 was not statistically significant. Both doses studied (150 and 300 mg/d) were effective at week 1 and generally well tolerated.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome; Young Adult

evaluate the efficacy (time to recurrence of depressive symptoms) of once daily extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy treatment to prevent relapse for major depressive disorder (MDD).. Time-to-event (maximum 52 weeks), double-blind, multicenter, randomized withdrawal, placebo-controlled study of quetiapine XR (50-300 mg/day) comprising four treatment phases: enrollment (up to 28 days), open-label run-in (4-8 weeks), open-label stabilization (12-18 weeks), and randomization (up to 52 weeks). Seven hundred and seventy-six patients stabilized on quetiapine XR were eligible for randomization (Montgomery-Åsberg Depression Rating Scale [MADRS] score ≤12 and Clinical Global Impression-Severity of Illness [CGI-S] score ≤3); 391 received quetiapine XR and 385 received placebo (same dose as last open-label visit). Primary endpoint: time to recurrence of depressive event from randomization. Secondary outcomes included changes from randomization in MADRS total, CGI-S, Pittsburgh Sleep Quality Index (PSQI) global, and Hamilton Anxiety Rating Scale (HAM-A) total scores. Adverse events were recorded throughout.. Risk of recurrence of depressive event was significantly (P<.001) reduced by 66% (HR=.34; 95% CI: .25, .46) in patients randomized to continue with quetiapine XR versus patients randomized to switch to placebo. During the randomized phase, quetiapine XR maintained improvements in secondary outcomes (P<.001 for all): MADRS (0.15 versus 2.03), CGI-S (-0.03 versus 0.23); PSQI global (0.06 versus 1.35), and HAM-A total score (0.20 versus 1.58), respectively. The most common AEs (>10% any group) during the randomized period were headache and insomnia.. Quetiapine XR maintenance therapy significantly reduced the risk of a depressive event in patients with MDD stabilized on quetiapine XR, with a safety and tolerability profile consistent with the known profile of quetiapine.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Placebos; Proportional Hazards Models; Psychiatric Status Rating Scales; Quetiapine Fumarate; Secondary Prevention; Severity of Illness Index; Treatment Outcome; Young Adult

Perimenopausal and early postmenopausal women have shown an increased risk for developing depression (new onset or recurrent); concomitant vasomotor and other menopause-related complaints significantly affect quality of life and overall functioning. This study examined the effects of quetiapine extended release (XR) in midlife women with major depressive disorder who also reported significant menopause-related symptoms. Forty eligible women with major depressive disorder entered a 2-week, placebo lead-in phase, followed by an 8-week open trial with quetiapine XR, flexible dose, 150-300 mg/d. The primary outcome measure (depressive symptoms) was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Other measures included menopause symptoms (Greene Climacteric Scale total scores and subscores) and the impact of hot flashes on functioning (Hot Flash-Related Daily Interference Scale). Weight, cholesterol, triglycerides, and glucose levels were monitored. Data from 24 subjects (modified intent-to-treat, last observation carried forward; quetiapine XR mean dose, 191 [SD, 55] mg/d) showed improvement in depressive and menopause-related symptoms, that is, reduction in MADRS, GCS, and Hot Flash-Related Daily Interference Scale scores (P < 0.01 for all comparisons). Seventeen subjects were considered responders (>50% reduction in MADRS scores); 15 achieved remission (MADRS<10). Main adverse effects included drowsiness and dry mouth. Based on these preliminary results, quetiapine XR should be further examined in larger, controlled trials for the management of depressed, symptomatic midlife women.

Topics: Adult; Affect; Age Factors; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Hot Flashes; Humans; Menopause; Middle Aged; Pilot Projects; Quetiapine Fumarate; Single-Blind Method

Atypical antipsychotics may have efficacy as augmentation therapy in treatment resistant depression (TRD) but evidence is limited.. An open label study of quetiapine augmentation in 24 patients (mean age: 46.3 years) with a DSM-IV major depressive episode resistant to at least 2 trials of antidepressant medication, and currently taking a monoamine reuptake inhibitor. An 8-week treatment phase was followed by an 18-week extension in patients who showed clinical benefit.. Eighteen patients (75%) completed the 8-week treatment phase with seven patients (29%) being responders on the Montgomery Asberg Depression Rating Scale and 13 (54%) on the CGI-I. Fewer patients responded if they had previously received olanzapine in the current episode but this was not statistically significant (0% v 37%, p=0.27). Of the eleven patients entering the extension phase, 3 patients (27%) experienced a significant worsening of mood. The most common adverse events were sedation (54%), dry mouth (38%) and dizziness (29%). Significant weight gain was found in 40% of patients treated for 26 weeks. Average quetiapine doses were 245 mg at 8 weeks and 346 mg at 26 weeks.. Quetiapine may be a helpful adjunctive agent for some patients with TRD but placebo-controlled trials are needed to establish its place in management.. The trial was open-label and the numbers were small.

Topics: Adult; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Dizziness; Drug Administration Schedule; Drug Resistance; Female; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Weight Gain

This 6-week, randomized, double-blind study evaluated efficacy and safety of adjunctive extended-release (XR) quetiapine in patients with major depressive disorder (MDD) and an inadequate response to >or= 1 antidepressant.. Male or female patients aged 18 to 65 years with DSM-IV-TR MDD were randomly assigned to receive quetiapine XR (150 or 300 mg/day) or placebo adjunctive to continuing antidepressant. Primary endpoint was change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Secondary variables included MADRS response (>or= 50% reduction in score from randomization) at weeks 1 and 6, MADRS remission (

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Severity of Illness Index; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Young Adult

To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy treatment for major depressive disorder (MDD).. This 8-week (6-week active-treatment, randomized phase; 2-week posttreatment drug-discontinuation/tapering phase), multicenter, double-blind, randomized, parallel-group, placebo- and active-controlled, phase 3 study was conducted between April 2006 and May 2007. In total, 612 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-defined MDD were randomly assigned to quetiapine XR 150 mg/day or 300 mg/day, duloxetine 60 mg/day (active control), or placebo. The primary endpoint was the change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score.. At week 6, both doses of quetiapine XR (p < .001) and duloxetine (p < .01) significantly reduced mean MADRS total score versus placebo. A significant reduction was seen at week 1 with quetiapine XR 150 mg/day and 300 mg/day versus placebo (p < .01), but not with duloxetine. Response rates (>or= 50% reduction in MADRS total score) at week 6 were significantly higher for both doses of quetiapine XR (p < .01) and duloxetine (p < .05) versus placebo. Remission rates (MADRS score

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Duloxetine Hydrochloride; Female; Humans; Male; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Thiophenes

Once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy was evaluated in major depressive disorder (MDD).. This was an 8-week (6-week randomized-phase; 2-week drug-discontinuation/tapering phase), double-blind, parallel-group, placebo-controlled study. The primary outcome measure was Montgomery-Asberg Depression Rating Scale (MADRS) total score randomization-to-Week 6 change. Other assessments included the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, and adverse events (AEs).. 723 patients were randomized: 182, 178, 179, and 184 to quetiapine XR 50, 150, 300 mg/day, and placebo, respectively. At Week 6, significant reductions occurred in MADRS score with quetiapine XR 50 mg/day (-13.56; P<.05), 150 mg/day (-14.50; P<.01) and 300 mg/day (-14.18; P<.01) versus placebo (-11.07); at Day 4, reductions for quetiapine XR (titrated to 50 or 150 mg/day according to dose group) versus placebo (-2.9) were: -4.7 (P<.01), -5.2 (P<.001), and -5.1 (P<.001), respectively. At endpoint, MADRS response (>or=50% reduction in score) was 42.7% (P<.01), 51.2% (P<.001), and 44.9% (P

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Electrocardiography; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

The objective of this study was to investigate whether quetiapine, when compared with placebo, can speed the onset of action and improve the quality of response to fluoxetine treatment in patients suffering from major depressive disorder. A total of 114 patients with major depressive disorder were enrolled in an 8-week treatment study. Patients were initiated on a course of fluoxetine treatment and randomized to quetiapine or placebo. Quetiapine was flexibly dosed starting at 25 mg to a maximum of 100 mg daily. Mixed-effects regression showed that quetiapine plus fluoxetine did not achieve 50% reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale, Clinical Global Improvement (CGI)-Severity, and CGI-Improvement scores sooner than the fluoxetine plus placebo group; however both groups improved in all scores over time. Mixed-effects linear regression of insomnia scores showed that the quetiapine plus fluoxetine group improved significantly more rapidly compared with the fluoxetine plus placebo group. The study indicates that quetiapine plus fluoxetine did not achieve a reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale or CGI scores from baseline sooner than the fluoxetine plus placebo group. The combination of quetiapine and fluoxetine, however, improved sleep over fluoxetine alone over the first few weeks of treatment.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Female; Fluoxetine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Regression Analysis; Treatment Outcome

Patients with major depression refractory to repeated pharmacological trials (TRD) may remain symptomatic for many years after their index episode. Augmentation strategies (with lithium or an atypical antipsychotic) or combining an antidepressant with short-term psychotherapy have been used with relative success in these patients. The aim of this study was to assess the effectiveness of the concomitant administration of quetiapine, an atypical antipsychotic, or placebo, to cognitive-behavior therapy (CBT) in TRD.. Thirty-one patients who met entrance criteria for unipolar major depression (TRD stage II or greater) underwent 3 weeks of lithium augmentation after which non-responders (N = 22) were randomized to receive either quetiapine or placebo as an adjunct to their 12 weekly CBT sessions (quetiapine/CBT or placebo/CBT groups). Primary efficacy measures were the Hamilton and the Montgomery-Asberg rating scales for depression.. Overall, there was a significant reduction in both primary efficacy measure scores at LOCF for the 11 patients in the quetiapine/CBT group but not in the placebo/CBT treated patients. Patients in the quetiapine/CBT group, compared to those receiving placebo/CBT, showed a significantly greater degree of improvement on one primary and one secondary efficacy measure, were more likely to complete the trial and, completed a greater number of CBT sessions.. Although preliminary, our results suggest that the adjunctive administration of quetiapine to CBT may prove useful in the treatment of stage II TRD.. Current Controlled Trials ISRCTN12638696.

Topics: Adult; Aged; Antipsychotic Agents; Cognitive Behavioral Therapy; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Young Adult

To investigate the efficacy and tolerability of quetiapine monotherapy for the treatment of major depressive episodes in patients with bipolar I disorder, as a post hoc analysis of data from 2 large studies, the BipOLar DEpRession (BOLDER) I and II studies, which investigated the overall efficacy of quetiapine in both bipolar I and II disorder.. A combined cohort of patients with depressive episodes in bipolar I disorder (DSM-IV criteria) (N = 694) from 2 nearly identical double-blind, randomized, placebo-controlled studies that each randomly assigned patients with bipolar I and II disorder to 8 weeks of treatment with quetiapine 300 or 600 mg/day or placebo was analyzed. The primary efficacy measure was change from baseline to end of treatment (week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores.. In the combined cohort of patients with depressive episodes in bipolar I disorder from 2 studies, there were significantly greater clinical improvements in mean MADRS total scores among patients who received quetiapine compared with placebo from baseline to week 1 and through week 8 (at week 8: quetiapine 300 mg/day = -19.4; 600 mg/day = -19.6; placebo = -12.6; p < .001 for each dose), providing effect sizes of 0.78 and 0.80, respectively. Changes in MADRS were unrelated to reports of sedation and somnolence. The most common adverse events (AEs) with quetiapine were dry mouth, somnolence, sedation, dizziness, and constipation. Rates of withdrawal because of these AEs were relatively low.. Quetiapine monotherapy (300 and 600 mg/day) is more effective than placebo and generally well tolerated for the treatment of depressive episodes in patients with bipolar I disorder.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Mass Screening; Quetiapine Fumarate; Treatment Outcome

This double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with selective serotonin reuptake inhibitors (SSRIs)/venlafaxine in 58 patients with major depressive disorder, comorbid anxiety symptoms (HAM-A-14 score > or =14), and residual depressive symptoms (HAM-D-17 score > or =18, CGI-S score > or =4). Patients had received an SSRI/venlafaxine (at a predefined therapeutic dose) for > or =6 weeks. Overall, 62% (18/29) of quetiapine- and 55% (16/29) of placebo-treated patients completed the study. The mean change in HAM-D and HAM-A total scores from baseline to Week 8 (primary endpoint) was significantly greater with quetiapine (mean dose 182 mg/day) than placebo: -11.2 vs. -5.5 (P=.008) and -12.5 vs. -5.9 (P=.002), respectively. The onset of quetiapine efficacy (HAM-D/HAM-A/CGI-I) was rapid (by Week 1) and continued through to Week 8. Significant differences (P<.05) from baseline to Week 8 were observed between groups in 7/17 HAM-D (including feelings of guilt, suicide) and 6/14 HAM-A items (including tension, cardiovascular symptoms). Response (> or =50% decrease in total score) was higher for quetiapine than placebo: HAM-D, 48% vs. 28% (not significant, NS); HAM-A, 62% vs. 28% (P=.02). Remission (total score < or =7) was higher for quetiapine than placebo: HAM-D, 31% vs. 17% (NS); HAM-A, 41% vs. 17% (NS). CGI-S, CGI-I, and the Global Assessment Scale showed that quetiapine was significantly more effective than placebo. For quetiapine, adverse events (AEs) were similar to those previously observed; sedation/somnolence/lethargy was the most commonly reported. Here quetiapine was shown to be effective as augmentation of SSRI/venlafaxine therapy in patients with major depression, comorbid anxiety, and residual depressive symptoms, with no unexpected tolerability issues. Further studies are warranted.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Anxiety Disorders; Comorbidity; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Personality Inventory; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride

To investigate the effects of antidepressant therapy plus quetiapine on major depression, motor activity, daytime sleepiness and quality of sleep.. Patients (N = 27) with major depressive disorder received a standard antidepressant treatment (Venlafaxine, Escitalopram) plus flexible dose of quetiapine. Patients' depression was monitored with HAM-D-21, motor activity was continuously measured with actigraphy and sleep parameters with the Pittsburgh Sleep Quality Index (PSQI) over 4 weeks.. Whereas depression, quality of sleep and daytime sleepiness showed a significant improvement over 4 weeks, change of daytime motor activity was significant only between the wash out period and the last 2 days of the study. Repeated measures of variance indicate an independent influence of quetiapine on improved depression, motor activity and sleep. While we found only a mild decrease of daytime sleepiness during the first week of treatment, the further decline of daytime sleepiness got significant after 2 weeks of treatment with quetiapine, even at high mean daily doses and despite the sedative effects of quetiapine.. Antidepressant treatment plus quetiapine is possibly a suitable treatment strategy to improve clinical depression, quality of sleep and motor activity. Future research is needed to understand the pharmacological interactions between antidepressants and quetiapine in major depression.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Arousal; Bipolar Disorder; Circadian Rhythm; Citalopram; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Motor Activity; Quetiapine Fumarate; Sleep; Treatment Outcome; Venlafaxine Hydrochloride

Quetiapine monotherapy shows efficacy in bipolar depression. The analyses in this multicenter, double-blind, randomized, fixed-dose, placebo-controlled study evaluated effects of quetiapine monotherapy on anxiety symptoms in bipolar depression.. Of 542 outpatients randomly assigned to treatment, 539 with bipolar I (N = 358) or bipolar II (N = 181) disorder experiencing a major depressive episode (DSM-IV) received 8 weeks of quetiapine monotherapy (600 or 300 mg/day) or placebo between September 2002 and October 2003. Anxiety assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and relevant items from the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Rating Scale for Depression (HAM-D). Analyses evaluated the pooled dose groups versus placebo.. At week 8, quetiapine 600 and 300 mg/day each demonstrated significant improvements in HAM-A total score versus placebo (-10.8 and -9.9 vs. -6.7, p < .001). Quetiapine (pooled doses) significantly improved HAM-A total score from week 1. In bipolar I depression, quetiapine showed significant improvement in HAM-A total score versus placebo (-10.4 vs. -5.1, p < .001). In bipolar I depression, quetiapine also showed significant improvements versus placebo on the HAM-A anxious mood and tension items, HAM-A psychic and somatic subscales, MADRS inner tension item, and HAM-D psychic anxiety item (all p < .001), but not the HAM-D somatic anxiety item. In bipolar II depression, quetiapine reduced the HAM-A total score more than placebo, but the difference was not statistically significant (-9.8 vs. -9.0, p = .473). In bipolar II depression, quetiapine showed significant improvement versus placebo on the HAM-A anxious mood, MADRS inner tension, and HAM-D psychic anxiety items (all p < .01).. Quetiapine monotherapy shows efficacy in treating anxiety symptoms in bipolar I depression; however, the anxiolytic effects in bipolar II disorder require further investigation.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Comorbidity; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Longitudinal Studies; Male; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Treatment-resistant depression (TRD) is a common clinical problem, often complicated with suicidal ideations and greater lifetime functional impairment, and represents a considerable challenge to management and treatment.. The aim of a prospective, open-label, noncomparative, flexible-dosed 20-week study was to evaluate the effects of quetiapine, as an add-on therapy, in patients with TRD who were refractory to previous treatments.. Eighteen patients with major depressive disorder (DSM-IV criteria) were treated for 20 weeks with quetiapine (mean dose 315+/-109 mg/day). Patients were evaluated at baseline, weekly from 1 to 9 weeks, and then after 12, 16, and 20 weeks of treatment, using Hamilton rating scale for depression-17 items (HAMD) scale.. Fourteen patients with TRD completed the 20-week open trial with quetiapine. The augmentation with quetiapine significantly reduced total scores and scores listed in the anxiety subscale on the HAMD, and these effects were observed after the fourth week of treatment, while the depressed mood scores were significantly reduced after the fifth week of treatment. Quetiapine add-on treatment significantly decreased the scores listed in the insomnia subscale on the HAMD subscale after the second week of treatment.. Our preliminary data indicate that quetiapine add-on therapy appears to have beneficial effects in the treatment of patients with TRD.

Topics: Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Time Factors; Treatment Outcome

The response of obsessive-compulsive disorder (OCD) to serotonin reuptake inhibitors (SRIs) is often inadequate. Case series reporting successful augmentation with risperidone and olanzapine led us to investigate quetiapine in OCD that was resistant to SRI treatment.. In this 8-week, 2-site (S1, S2), open-label trial, 30 adults (16 at S1 and 14 at S2) with a DSM-IV diagnosis of OCD, SRI-resistant, received augmentation with quetiapine, with the dose doubled every 2 weeks from 25 mg to 200 mg/day. Primary outcome was measured with the Yale-Brown Obsessive Compulsive Scale (YBOCS). A response was defined as a > or = 25% decrease from the baseline YBOCS score.. Significant differences between the sites in patient characteristics (7/14 at S2 were hoarders, i.e., more treatment resistant, vs. 1/16 at S1; p = .01) and in quetiapine treatment (mean +/- SD dose of 116 +/- 72 mg/day at S2 vs. 169 +/- 57 mg/day at S1; p = .039) necessitated separate analysis of results. At S1, the mean +/- SD YBOCS score fell significantly from 27.7 +/- 7.0 to 23.3 +/- 8.4 (t = 2.96, df = 15, p = .01), and the responder rate was 31% (5/16). At S2, the mean YBOCS score did not decrease significantly, and the responder rate was 14% (2/14). Most adverse medication events were mild or moderate. Two subjects (13%) at S1 and 3 (21%) at S2 withdrew due to adverse events.. The results at S1 resemble those reported with other atypical antipsychotics and suggest that quetiapine augmentation may benefit treatment-resistant OCD. The poorer results at S2 may reflect the large proportion of hoarders or the less intense treatment. Longer, higher dose, large, double-blind, placebo-controlled comparison trials of atypical antipsychotics are needed.

Topics: Antipsychotic Agents; Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.

Topics: Aged; Citalopram; Depressive Disorder, Major; Escitalopram; Humans; Long QT Syndrome; Psychotropic Drugs; Quetiapine Fumarate

Major depressive disorder (MDD) etiology is still not completely understood, and many individuals resist the traditional treatments. Chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, inflammatory changes and oxidative balance are associated with MDD pathophysiology. Quetiapine, a second-generation antipsychotic, induces a better therapeutic response in individuals refractory to traditional treatments. The main objectives of this research were as follows: to evaluate the effect of chronic mild stress (CMS) on depressive-like behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant, and anti-inflammatory effects of quetiapine. The animals were submitted to CMS protocols. At the end of the CMS, the animals were submitted to a chronic treatment for 14 days with the following drugs: quetiapine (20 mg/kg), imipramine (30 mg/kg), and escitalopram (10 mg/kg). At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. The animals were euthanized after the behavioral tests, and serum samples were collected. Myeloperoxidase (MPO) activity and interleukin-6 (IL-6) levels were analyzed. CMS induced an increase in depressive-like behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is a relevant phenomenon in the etiology of depression and suggesting that quetiapine induces an antidepressant effect because it reduces oxidative and inflammatory mechanisms.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Depression; Depressive Disorder, Major; Disease Models, Animal; Inflammation; Interleukin-6; Oxidative Stress; Quetiapine Fumarate; Rats; Stress, Psychological

The second-generation antipsychotic (SGA) quetiapine is an essential option for antidepressant augmentation therapy in major depressive disorder (MDD), yet neurobiological mechanisms behind its antidepressant properties remain unclear. As SGAs interfere with activity in reward-related brain areas, including the anterior cingulate cortex (ACC) - a key brain region in antidepressant interventions, this study examined whether quetiapine treatment affects ACC activity during reward processing in MDD patients.. Using the ACC as region of interest, an independent t-test comparing reward-related BOLD response of 51 quetiapine-taking and 51 antipsychotic-free MDD patients was conducted. Monetary reward outcome feedback was measured in a card-guessing paradigm using pseudorandom blocks. Participants were matched for age, sex, and depression severity and analyses were controlled for confounding variables, including total antidepressant medication load, illness chronicity and acute depression severity. Potential dosage effects were examined in a 3 × 1 ANOVA. Differences in ACC-related functional connectivity were assessed in psycho-physiological interaction (PPI) analyses.. Left subgenual ACC activity was significantly higher in the quetiapine group compared to antipsychotic-free participants and dependent on high-dose quetiapine intake. Results remained significant after controlling for confounding variables. The PPI analysis did not yield significant group differences in ACC-related functional connectivity.. Causal interpretation is limited due to cross-sectional findings.. Elevated subgenual ACC activity to rewarding stimuli may represent a neurobiological marker and potential key interface of quetiapine's antidepressant effects in MDD. These results underline ACC activity during reward processing as an investigative avenue for future research and therapeutic interventions to improve MDD treatment outcomes.

Topics: Antidepressive Agents; Antipsychotic Agents; Cross-Sectional Studies; Depressive Disorder, Major; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Quetiapine Fumarate; Reward

Quetiapine is a drug used to treat schizophrenia, bipolar disorder, and major depressive disorder. However, it can cause mild or severe hepatic adverse events and rarely fatal liver damage. This study was aimed at investigating hepatic toxicity caused by quetiapine use by analyzing the information captured from hospital electronic health records by using the Observational Medical Outcomes Partnership common data model (CDM).. This was a retrospective observational study involving a nested case-control method. A CDM based on an electronic health record database from five hospitals between January 2009 and May 2020 was used. We analyzed the status of quetiapine use, adverse events, and hepatic impairment.. The numbers of patients with non-serious and severe hepatic adverse reactions were 2566 (5.05%) and 835 (1.64%) out of 50 766 patients, respectively. After adjusting for covariates, the odds ratio of hepatic adverse events was 2.35 (95% CI: 2.03-2.72), and the odds ratio of severe hepatic adverse events was 1.76 (95% CI: 1.16-2.66).. Our findings suggest that quetiapine should be cautiously used, and hepatic function should be monitored in patients using quetiapine because it can cause mild or severe hepatic adverse events, complications, and in rare cases, fatal liver damage.

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Humans; Liver; Quetiapine Fumarate

Hepatocellular carcinoma (HCC) is the primary tumor of the liver and the fourth leading cause of cancer-related death. Recently, several studies indicated the anti-tumor potential of antipsychotic medicine. Quetiapine, an atypical antipsychotic, is used to treat schizophrenia, bipolar disorder, and major depressive disorder since 1997. However, whether quetiapine may show potential to suppress HCC progression and its underlying mechanism is persisting unclear. Quetiapine has been shown to induce apoptosis and inhibit invasion ability in HCC in vitro. Here, we established two different HCC (Hep3B, SK-Hep1) bearing animals to identify the treatment efficacy of quetiapine. Tumor growth, signaling transduction, and normal tissue pathology after quetiapine treatment were validated by caliper, bioluminescence image, immunohistochemistry (IHC), and hematoxylin and eosin staining, respectively. Quetiapine suppressed HCC progression in a dose-dependent manner. Extracellular signal-regulated kinases (ERKs) and Nuclear factor-κB (NF-κB) mediated downstream proteins, such as myeloid leukemia cell differentiation protein (MCL-1), cellular FLICE-inhibitory protein (C-FLIP), X-linked inhibitor of apoptosis protein (XIAP), Cyclin-D1, matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor-A (VEGF-A) and indoleamine 2,3-dioxygenase (IDO) which involved in proliferation, survival, angiogenesis, invasion and anti-tumor immunity were all decreased by quetiapine. In addition, extrinsic/intrinsic caspase-dependent and caspase-independent pathways, including cleaved caspase-3, -8, and - 9 were increased by quetiapine. In sum, the tumor inhibition that results from quetiapine may associate with ERK and NF-κB inactivation.

Topics: Animals; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Depressive Disorder, Major; Extracellular Signal-Regulated MAP Kinases; Liver Neoplasms; NF-kappa B; Quetiapine Fumarate; Vascular Endothelial Growth Factor A

Augmentation with second-generation antipsychotics (SGAs) represents an evidence-based psychopharmacotherapeutic strategy recommended in case of insufficient response to the first-line antidepressant (AD) treatment in major depressive disorder (MDD). Comparative evidence regarding efficacy and prescription preferences of the individual SGAs is scarce.. In the scope of this European, multi-site, naturalistic cross-sectional investigation with retrospective assessment of treatment outcome, we compared sociodemographic and clinical characteristics of 187 MDD patients receiving either quetiapine (n = 150) or aripiprazole (n = 37) as augmentation of their first-line AD psychopharmacotherapy.. Comorbid posttraumatic stress disorder and diabetes were significantly associated with aripiprazole augmentation in our primary and post-hoc binary logistic regression analyses. Furthermore, we identified an association between aripiprazole co-administration and the presence of additional psychotic features, higher rates of AD combination treatment, and a longer duration of psychiatric hospitalizations during the lifetime, which, however, lost significance after correcting for multiple comparisons. Regarding treatment outcome, we found a trend of higher response rates and greater reductions in severity of depressive symptoms in MDD patients dispensed quetiapine.. Factors associated with a more chronic and severe profile of MDD seem to encourage clinicians to choose aripiprazole over quetiapine, that was, however, administered in the majority of our MDD patients, which might reflect the current approval situation allowing to prescribe exclusively quetiapine as on-label augmentation in MDD in Europe. Given the retrospective assessment of treatment response, the markedly smaller proportion of patients receiving aripiprazole augmentation generally showing an unfavorable disease profile, and the partially heterogeneous statistical robustness of our findings, further studies are required to elaborate on our observation and to generate unambiguous recommendations regarding the choice of first-line SGA augmentation in MDD.

Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Cross-Sectional Studies; Depressive Disorder, Major; Drug Therapy, Combination; Europe; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome

Norbuprenorphine interferences were observed in urine drug testing LC-MS-MS confirmation methods used to assess patient compliance with prescribed buprenorphine for chronic pain and opioid use disorder. The interferences were observed in the norbuprenorphine MS-MS transitions, m/z 414.4/83.1 and 414.4/187.2, at and near the norbuprenorphine retention time at multiple laboratories using different sample preparation procedures and chromatographic conditions. When the interferences were present, a norbuprenorphine result could not be reported. Upon investigation, the interferences were correlated with prescribed quetiapine (Seroquel, Seroquel XR), a second-generation antipsychotic medication approved for the treatment of schizophrenia, bipolar disorder and more recently as an adjunct treatment for major depressive disorder. In addition to the approved indications, quetiapine is prescribed off-label for other conditions including insomnia and anxiety disorders. Off-label prescribing has increased in recent years, thereby exacerbating this analytical issue. Here, we present the study of four quetiapine metabolites found to have significant direct or potential interferences in norbuprenorphine quantitation. The four metabolites were putatively identified as two hydroxyquetiapine acids differing in the site of hydroxylation and a quetiapine sulfoxide acid diastereomer pair. As a result of this study, interference-free norbuprenorphine MS-MS transitions, m/z 414.4/340.2 and 414.4/326.1, were found that were selective for norbuprenorphine while maintaining an acceptable 10 ng/mL lower limit of quantitation.

Topics: Buprenorphine; Chromatography, Liquid; Depressive Disorder, Major; Humans; Quetiapine Fumarate; Tandem Mass Spectrometry

The efficacy of vortioxetine in major depressive disorder has been evaluated in many studies. However, there is a lack of studies assessing vortioxetine in bipolar depression.. In 60 patients with bipolar depression, vortioxetine 10-20 mg daily was added to current mood stabilizing medication during 24-week, naturalistic, openlabel study. The most frequent mood stabilizers were lamotrigine, quetiapine, olanzapine, and valproates. The therapeutic efficacy was evaluated by the Clinical Global Impression - Improvement (CGI-I) and Clinical Global Impression - Severity (CGI-S) scales. Patients were classified as responding to vortioxetine when they achieved 1 or 2 points on the CGI-I scale at any stage of observation. The criterion of remission was defined as score 1 at the CGI-S.. 73% of all patients (44/60) responded to vortioxetine and 52% (31/60) achieved clinical remission of depressive symptoms (in mean 8.97 ± 4.05 weeks). There were no significant associations between vortioxetine response/remission rates and: (1) the dose, (2) BD type, (3) clinical stage, (4) presence of rapid cycling, (5) history of psychotic symptoms, analyzed depressive symptoms, and (6) concomitantly used mood stabilizer. 4 patients (6.7%) stopped treatment due to adverse effects (nausea), and 7 patients (11.7%) discontinued treatment due to the phase switch. 14 patients (23%) experienced a loss of vortioxetine effectiveness after the initial response or remission.. The results indicate relatively high rates of response and remission during 24-week treatment in depressed bipolar patients receiving vortioxetine concomitantly with a mood stabilizer. This may indicate that vortioxetine added to a mood stabilizer may constitute an efficient and well tolerated therapeutic option in bipolar depression.

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Double-Blind Method; Humans; Quetiapine Fumarate; Treatment Outcome; Vortioxetine

Restless arms syndrome (RAS) is characterized by uncomfortable aching or burning sensations in the arms. RAS is regarded as an upper limb variant of restless legs syndrome (RLS). The lack of specific diagnostic criteria makes it difficult to recognize the RAS. Therefore, RAS is usually neglected in clinical practice. Moreover, when a patient was diagnosed with RAS, the adjustment of medications was the first choice for doctors, which may make the patient's condition unstable.. A 33-year-old woman was diagnosed with schizophrenia and major depressive disorder. Starting with 0.6 g/d amisulpride, 0.1 g/d quetiapine, 75 mg/d venlafaxine sustained-release tablets, the patient reported symptoms of RAS (itching arms) on the fourth day since the latest hospitalization. After ruling out other factors, her RAS was suspected to be induced by antidepressants or antipsychotics. Without medication adjustment, RAS spontaneously remitted.. This case suggests that psychiatrists should pay attention to RAS when using antipsychotics and/or antidepressants. Moreover, RAS may be transitory. When a patient manifests RAS, observation may be one choice instead of an immediate medication adjustment.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Female; Humans; Quetiapine Fumarate; Restless Legs Syndrome

Topics: Adult; Agoraphobia; Antibodies, Monoclonal, Humanized; Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Depressive Disorder, Major; Female; Humans; Lithium Carbonate; Male; Mental Disorders; Middle Aged; Nordazepam; Panic Disorder; Paroxetine; Psoriasis; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Valproic Acid

Idiopathic intracranial hypertension (IIH) is a condition associated with poor vision and headaches that can cause disability and reduced quality of life. The onset of IIH is typically associated with sudden weight gain and obesity, which may be due to first-generation or second-generation antipsychotics. This case involved the use of quetiapine in an obese, 28-year-old woman; she gained significant weight after starting the antipsychotic and later developed headaches and blurred vision. Reducing quetiapine and administering acetazolamide significantly improved her symptoms within 4 weeks. This case reminds physicians to consider IIH as a cause of headache and vision loss in patients who have gained weight after starting or increasing quetiapine.

Topics: Acetazolamide; Adult; Antipsychotic Agents; Depressive Disorder, Major; Drug Substitution; Female; Headache; Humans; Intracranial Hypertension; Obesity; Quality of Life; Quetiapine Fumarate; Treatment Outcome; Vision, Low; Weight Gain

Lesion-based investigations of psychopathology have preceded contemporary network-neuroscience initiatives. However, brain-lesions detected in routine psychiatric practice are often considered incidental and therefore ignored. Here, we illustrate a strategy to combine individual subject-level lesion information with open-source normative functional-connectomics data to make putative, neuroscience-informed symptom interpretation. Specifically, we report a patient with left precuneus granulomatous lesion and seizures followed by two distinct symptoms - kinetopsia and delusions of nihilism and guilt - which had a differential treatment response. The lesion-based brain-mapping approach could identify correlated (default-mode) and anti-correlated (temporo-parieto-occipital) networks, which enabled a neurobiological formulation of these diverse clinical manifestations.

Topics: Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Brain Mapping; Brain Neoplasms; Depressive Disorder, Major; Diagnosis, Differential; Electroconvulsive Therapy; Female; Fluoxetine; Granuloma; Humans; Magnetic Resonance Imaging; Middle Aged; Parietal Lobe; Phenytoin; Quetiapine Fumarate; Schizophrenia, Paranoid; Seizures

The purpose of this study was to compare medication adherence, health care utilization, and cost among patients receiving adjunctive treatment for major depressive disorder (MDD) with brexpiprazole, quetiapine, or lurasidone.. Using Truven Health MarketScan® Commercial, Medicaid, and Medicare Supplemental Databases, we identified adults with MDD initiating adjunctive treatment with brexpiprazole, quetiapine, or lurasidone (index atypical antipsychotic [AAP]). We compared medication adherence and persistence measured by proportion of days covered (PDC) and treatment duration of index AAP, all-cause and psychiatric hospital care (hospitalization or emergency department visit), and medical costs during 6-month follow-up. Models performed included logistic regression for hospital care, linear regression for PDC and cost, and Cox proportional hazards regression for time to discontinuation, adjusting for demographic, clinical, and utilization differences during the 6 months before index AAP.. The total sample included 778 brexpiprazole, 626 lurasidone, and 3458 quetiapine therapy initiators. Adjusting for baseline differences, the risk of discontinuation of index AAP was statistically significantly higher for quetiapine than for brexpiprazole (hazard ratio [HR] = 1.13; 95% CI, 1.02-1.25; P = 0.023) and did not differ between lurasidone and brexipiprazole (HR = 1.14; 95% CI, 1.00-1.29; P = 0.054). The adjusted rate of all-cause hospitalization or emergency department visit in the postindex period was lowest for brexpiprazole at 27.4% (95% CI, 24.0%-31.0%), compared with 31.1% (95% CI, 27.3%-35.2%) for lurasidone and 35.3% (95% CI, 33.5%-37.1%) for quetiapine (P< 0.001 for all comparisons). Quetiapine users had increased all-cause costs compared with brexpiprazole users (estimate = $2309; 95% CI, $31-$4587; P = 0.047); all-cause medical costs did not differ between lurasidone and brexpiprazole (estimate = $913; 95% CI, $-2033 -$3859; P = 0.543). Adjusted psychiatric hospital care, psychiatric costs, and PDC did not differ significantly among the groups.. In patients with MDD and a variety of insurance types, brexpiprazole use was associated with statistically significantly lower risks of discontinuation, risk of hospital care (hospitalization and ED visits), and all-cause medical costs compared with adjunctive quetiapine. Differences between brexpiprazole and lurasidone were not statistically significant. These findings suggest that drug choice is associated with subsequent health care utilization and costs.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Depressive Disorder, Major; Emergency Service, Hospital; Female; Health Care Costs; Hospitalization; Humans; Lurasidone Hydrochloride; Male; Medicaid; Medicare; Medication Adherence; Middle Aged; Patient Acceptance of Health Care; Quetiapine Fumarate; Quinolones; Thiophenes; United States; Young Adult

Although the sedative and extrapyramidal side effects associated with first-generation antipsychotics are well known, some second-generation antipsychotics are also associated with substantial sedation and activation effects. In this Academic Highlights article, 4 experts on depression from the fields of psychiatry and primary care take a closer look at activation and sedation effects of atypical antipsychotics in patients with MDD. They examine the likelihood of each agent to cause these effects; the impact of these effects on patient functioning, quality of life, and treatment adherence; and the question of whether leveraging activation and sedation to address acute symptoms is ever advisable.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Arousal; Comorbidity; Delayed-Action Preparations; Depressive Disorder, Major; Drug Approval; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Practice Patterns, Physicians'; Quality of Life; Quetiapine Fumarate; Quinolones; Sleep Initiation and Maintenance Disorders; Thiophenes

To report dispensing of disulfiram, naltrexone, antidepressants and quetiapine for New Zealanders diagnosed with alcohol use disorder.. The Pharmaceutical Collection is the national dispensing database for medications in New Zealand. PRIMHD is the national mental health and addiction service database. Dispensing data was extracted from the Pharmaceutical Collection and merged with diagnostic data from PRIMHD to report pharmacological treatment of alcohol use disorders in New Zealand.. In 2014, there were 5,004 individuals diagnosed with an alcohol use disorder by mental health and addiction services. Four hundred and eighty-nine individuals also received a major depressive disorder diagnosis. 2.1% of the group with alcohol use disorder were dispensed disulfiram and 0.7% were dispensed naltrexone. Treatment with antidepressants (12.7%) and quetiapine (5.6%) was more common. In the group with comorbid alcohol use disorder and depression, 2% were dispensed disulfiram, 0.2% were dispensed naltrexone, 27.4% were dispensed antidepressants and 11.2% were dispensed quetiapine.. Overall rates of dispensing were relatively low. Antidepressants followed by quetiapine were the most common treatments. In contrast, disulfiram and naltrexone were only used for a minority of clients. This suggests inadequate and poorly targeted pharmacological treatments are used for the treatment of alcohol use disorders in New Zealand.

Topics: Alcohol Deterrents; Alcoholism; Antidepressive Agents; Depressive Disorder, Major; Disulfiram; Female; Humans; Male; Middle Aged; Naltrexone; New Zealand; Quetiapine Fumarate

Quetiapine is effective in treating depressive symptoms in major depressive disorder and bipolar disorder, but the mechanisms underlying its antidepressants effects are unknown. Norquetiapine, a metabolite of quetiapine, has high affinity for norepinephrine transporter, which might account for its therapeutic efficacy.. In this study, we used positron emission tomography with (S,S)-[11C]O-methyl reboxetine to estimate norepinephrine transporter density and assess the relationship between norepinephrine transporter occupancy by quetiapine XR and improvement in depression in patients with major depressive disorder (n=5) and bipolar disorder (n=5). After the baseline positron emission tomography scan, patients were treated with quetiapine XR with a target dose of 150 mg in major depressive disorder and 300 mg in bipolar disorder. Patients had a second positron emission tomography scan at the end of week 2 and a final scan at week 7.. Norepinephrine transporter density was significantly lower in locus ceruleus in patients compared with healthy subjects. Further, there was a significant positive correlation between quetiapine XR dose and norepinephrine transporter occupancy in locus ceruleus at week 2. The norepinephrine transporter occupancy at week 2 in hypothalamus but not in other regions predicted improvement in depression as reflected by reduction in MADRS scores from baseline to week 7. The estimated dose of quetiapine XR associated with 50% norepinephrine transporter occupancy in hypothalamus at week 2 was 256 mg and the estimated plasma levels of norquetiapine to achieve 50% norepinephrine transporter occupancy was 36.8 µg/L.. These data provide preliminary support for the hypothesis that norepinephrine transporter occupancy by norquetiapine may be a contributor to the antidepressant effects of quetiapine.

Topics: Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hypothalamus; Locus Coeruleus; Male; Middle Aged; Norepinephrine Plasma Membrane Transport Proteins; Positron-Emission Tomography; Quetiapine Fumarate; Reboxetine; Young Adult

This multicenter, observational drug utilization (DU) study (NCT01594996) investigated the profile of patients and specialist providers who prescribed extended release quetiapine fumarate (quetiapine XR) for treatment of major depressive disorder (MDD) across five European countries (Germany, Italy, Romania, Spain, and Sweden). A DU data abstraction form captured information on the characteristics of physicians, patients, and drugs utilized in the medical management of depressive episodes in MDD, where the therapeutic regimen included quetiapine XR. Data were reported descriptively. This analysis included 811 patients. Psychiatric histories indicated a burden of severe MDD in these patients. Patient demographics were similar across countries; however, those in Sweden had a younger mean age. Physicians' ratings of the therapeutic effect of prior treatment with antidepressants suggested the need for an add-on treatment for most patients. Overall, 15.7% of patients initiated quetiapine XR treatment as monotherapy. Presence of psychotic symptoms during depressive episodes predicted treatment with higher than recommended doses of quetiapine XR (odds ratio=3.11; 95% confidence interval: 1.6-6.0). This analysis demonstrated similarities in DU across the countries analyzed, largely in accordance with the recommended dose of quetiapine XR as an adjunctive therapy to antidepressants in MDD (50-300 mg/day).

Topics: Adult; Antidepressive Agents; Delayed-Action Preparations; Demography; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Utilization Review; Europe; Female; Humans; Male; Medication Therapy Management; Middle Aged; Practice Patterns, Physicians'; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate

Antipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents.. We obtained data on mental disorders from the Norwegian Patient Registry on 0-18 year olds who during 2009-2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database.. A total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009-2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%).. When a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Comorbidity; Depressive Disorder, Major; Female; Humans; Incidence; Infant; Male; Mental Disorders; Norway; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Complaints of hypoglycemia resemble the sedative effect of antipsychotics. As such, clinicians may overlook hypoglycemia in patients with psychiatric disorders. Here, a case of hypoglycemia associated with hyperinsulinemia induced by quetiapine in a female patient with bipolar disorder is reported. The case suggests that clinicians should be aware of the potential for hypoglycemia induced by second-generation antipsychotics.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Diagnostic Errors; Female; Humans; Hypoglycemia; Middle Aged; Quetiapine Fumarate

The study compared all-cause and major depressive disorder (MDD)-related healthcare resource use (HRU) and costs in patients with MDD treated with atypical antipsychotic (AAP) adjunctive therapy early or later in treatment.. Adults with MDD and antidepressant treatment (ADT) who newly initiated adjunctive aripiprazole, brexpiprazole, lurasidone, or quetiapine between October 1, 2014 and September 30, 2015 were identified in the IQVIA Real-World Data Adjudicated Claims database; the index date was the date of the first AAP claim. Patients were stratified into three cohorts: AAP initiated in the first year (Y1); in the second year (Y2); and more than 2 years (Y3) of first ADT use. Within each cohort, HRU and costs were compared between the 12 months before and after the index date. Pre-post changes in HRU and costs were then compared between cohorts.. Five hundred and six (36.7%) patients were categorized as Y1; 252 (18.3%) as Y2; and 622 (45.1%) as Y3. AAP use was associated with significantly decreased rates of all-cause and MDD-related hospitalization and emergency department visits, and increased rates of pharmacy fills and physician office visits; and the magnitude of changes was largest in cohort Y1. Cohort Y1 had the largest reductions in mean (±SD) all-cause medical costs per patient (-$10,496 ± $85,022, p = .015) compared to Y2 (-$2,474 ± $85,022, p = .572) and Y3 (-$472 ± $31,334, p = .823), mainly due to the reduction in hospitalization. After adjusting for differences in baseline characteristics, the largest reductions in hospitalization and medical costs were observed in cohort Y1. Similar increases in all-cause pharmacy costs were seen in all cohorts. A similar trend in costs was observed in MDD-related healthcare services.. AAP treatment was associated with reductions in all-cause and MDD-related medical costs, primarily in decreased hospitalization. The reductions were largest among patients who initiated treatment in the first year.

Topics: Adult; Age Factors; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Comorbidity; Depressive Disorder, Major; Drug Administration Schedule; Drug Therapy, Combination; Female; Health Expenditures; Health Resources; Health Services; Humans; Insurance Claim Review; Lurasidone Hydrochloride; Male; Middle Aged; Models, Econometric; Quetiapine Fumarate; Quinolones; Residence Characteristics; Retrospective Studies; Sex Factors; Socioeconomic Factors; Thiophenes; Time-to-Treatment

Antipsychotics produce electroencephalogram (EEG) modifications and increase the risk of epileptic seizure. These modifications remain sparsely studied specifically for atypical antipsychotics. In this context, our study focuses on EEG modifications associated with atypical strict antipsychotic monotherapies.. Electroencephalogram recordings of 84 psychiatric patients treated with atypical antipsychotics in strict monotherapy (clozapine, n = 22; aripiprazole, n = 22; olanzapine, n = 17; risperidone, n = 9; quetiapine, n = 8; risperidone long-acting injection, n = 4; and paliperidone long-acting injection, n = 2) were analyzed. The modifications were ranked according to both slowing and excitability scores.. Electroencephalogram modifications (in 51 subjects, 60.71%) were graded according to 4 stages combining general slowing and sharp slow waves and/or epileptiform activities. The presence of sharp or epileptiform activities was significantly greater for clozapine (90.9%) compared with other second-generation antipsychotics (aripiprazole, 50%; olanzapine, 58.8%; quetiapine, 37.5%; risperidone, 44.4%). Age, duration of disease progression, and diagnosis were not associated as risk factors. Electroencephalogram modifications were associated with lower doses for treatment with quetiapine but not for specific antipsychotics. Electroencephalogram modifications and severe excitability were associated with higher chlorpromazine equivalent doses.. Atypical antipsychotics (clozapine, aripiprazole, quetiapine, olanzapine, and risperidone) induce EEG modifications, and these are significantly greater for clozapine and appear dependent on chlorpromazine equivalent dose. No encephalopathy was observed in these antipsychotic monotherapies, whatever dose.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cerebral Cortex; Clozapine; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

The aim of the study was to evaluate baseline plasma VEGF levels as a potential predictor of response to antidepressant pharmacotherapy. The study also sought to determine whether baseline plasma VEGF would be useful in predicting treatment outcome when two pharmacodynamically diverse agents with established antidepressant efficacy, escitalopram and quetiapine, were administered monotherapeutically to MDD patients.. Two groups of qualifying MDD subjects were enrolled. One group was treated with escitalopram and the other with quetiapine. Plasma concentrations of VEGF were measured using Randox Technologies at baseline, and at weeks 8 and 12 of treatment.. We stratified the MDD patients into those who remitted and those who failed to respond. Mean baseline VEGF for the remitters and non-responders was 9.61  and 5.40 pg/ml, respectively (P < 0.0005). Using optimal data analysis a cut score of 7.49 pg/ml for baseline plasma VEGF distinguished remitters from non-responders with a 63% overall accuracy. The remission rate was comparable for both drugs (73 and 81% for quetiapine and escitalopram, respectively). VEGF levels did not significantly change following antidepressant treatment with either escitalopram or quetiapine when measured at 8 and 12 weeks; this result held true for both remitters and non-responders.. Our results suggest that VEGF may predict response to antidepressant treatment and may ultimately prove to be a potential biomarker that can be measured with a routine blood draw at the point of service.

Topics: Adult; Antidepressive Agents; Citalopram; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Quetiapine Fumarate; Remission Induction; Vascular Endothelial Growth Factor A

Symptom improvement in depression due to antidepressant treatment is highly variable and clinically unpredictable. Linking neuronal connectivity and genetic risk factors in predicting antidepressant response has clinical implications. Our investigation assessed whether indices of white matter integrity, serotonin transporter-linked polymorphism (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) val66met polymorphism predicted magnitude of depression symptom change following antidepressant treatment. Fractional anisotropy (FA) was used as an indicator of white matter integrity and was assessed in the uncinate fasciculus and superior longitudinal fasciculus using tract-based spatial statistics (TBSS) and probabilistic tractography. Forty-six medication-free patients with major depressive disorder participated in a diffusion tensor imaging scan prior to completing an 8-week treatment regime with citalopram or quetiapine XR. Indexed improvements in Hamilton Depression Rating Scale score from baseline to 8-week endpoint were used as an indicator of depression improvement. Carriers of the BDNF met allele exhibited lower FA values in the left uncinate fasciculus relative to val/val individuals [F(1, 40) = 7.314, p = 0.009]. Probabilistic tractography identified that higher FA in the left uncinate fasciculus predicted percent change in depression severity, with BDNF moderating this association [F(3, 30) = 3.923, p = 0.018]. An interaction between FA in the right uncinate fasciculus and 5-HTTLPR also predicted percent change in depression severity [F(5, 25) = 5.315, p = 0.002]. Uncorrected TBSS results revealed significantly higher FA in hippocampal portions of the cingulum bundle in responders compared to non-responders (p = 0.016). The predictive value of prefrontal and amygdala/hippocampal WM connectivity on antidepressant treatment response may be influenced by 5-HTTLPR and BDNF polymorphisms in MDD.

Topics: Adult; Antipsychotic Agents; Brain-Derived Neurotrophic Factor; Citalopram; Depressive Disorder, Major; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Young Adult

Major depressive disorder (MDD) is a debilitating psychiatric illness with a high cost burden. This analysis evaluates the cost-effectiveness of adjunctive brexpiprazole versus comparator branded adjunctive treatment for MDD and background antidepressant therapy (ADT) alone from a US payer perspective.. An economic model was developed to assess the cost-effectiveness of brexpiprazole versus comparator adjunctive treatment and ADT alone on total direct medical costs using a 6-week cycle time frame for a total of 48 weeks, with treatment response and remission as primary outcomes. The model consisted of 3 parts, 1 to represent the acute treatment phase and 2 to represent the maintenance stage.. In the base-case analysis, brexpiprazole as reference treatment resulted in cost per additional responder ranging from $19,442-$48,745 and cost per additional remitter ranging from $27,196-$71,839 versus comparator treatments over 48 weeks. Sensitivity analyses showed treatment with brexpiprazole was more costly, but more clinically effective in all probabilistic simulations.. This representation of disease natural history over 48 weeks may not account for all possible health states. Resource utilization on treatment was estimated using the resource use data from previous trials, and may overestimate medical costs compared to the real-world setting. Treatment comparators were limited to branded therapies, and head-to-head studies were not available to obtain data inputs.. Compared to other branded adjunctive therapies, brexpiprazole increases response and remission at 6 weeks; medical care cost savings were observed with the use of brexpiprazole. These findings may assist clinicians and formulary decision makers when selecting treatment for MDD.

Topics: Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Depressive Disorder, Major; Disorders of Excessive Somnolence; Drug Costs; Drug Therapy, Combination; Fatigue; Female; Health Care Costs; Humans; Male; Middle Aged; Models, Economic; Olanzapine; Patient Selection; Quetiapine Fumarate; Quinolones; Serotonin Agents; Thiophenes; Weight Gain; Young Adult

A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs.. A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date.. AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32-1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78-1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date.. The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations, while also examining methods to account for differences in older adults who do and do not use these medications.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR).. Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8 weeks (schizophrenia = 153, major depression = 200, bipolar depression = 252, other psychiatric conditions = 60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS).. The mean dose of quetiapine XR during follow-up was 195.6 ± 154.8 mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7 ± 0.1 points and 25.1 ± 0.9 points. Adverse events were observed in 34 and 26 % of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS ≥20 points (n = 292, 43 %) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C ≥5, n = 610, 93 %) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence.. Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR. Clinicaltrials.gov registration number NCT02409823.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Patient Compliance; Prospective Studies; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Schizophrenia; Sleep Stages; Treatment Outcome; Weight Gain

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Electrocardiography; Humans; Long QT Syndrome; Male; Middle Aged; Quetiapine Fumarate

This study investigated extended release quetiapine (quetiapine XR) associated changes in functional MRI (fMRI) measures of task-induced amygdalar activation and resting state connectivity in anxious unipolar major depressive disorder (AMDD).. Anxious unipolar major depressive disorder patients (n = 15) (17-item Hamilton Depression Rating Scale (HAM-D) >18 and Hamilton Anxiety Scale (HAM-A) >18) and closely matched healthy control (HC) subjects were compared at baseline for task induced amygdala activation and resting state connectivity on fMRI. Subsequently, AMDD patients were treated for 8 weeks with open-label quetiapine XR. Weekly HAM-D and HAM-A ratings were obtained, and the fMRI scan was repeated at weeks 2 and 8. Changes in fMRI measures were calculated using repeated-measures analysis of variance and correlation with decrease in HAM-D and HAM-A scores was examined.. At baseline, AMDD compared with HC exhibited increased task-induced left amygdalar activation (P = 0.05 clusterwise corrected) and decreased resting state amygdala-cortical and amygdala-pons connectivity (P < 0.05 clusterwise corrected). Quetiapine XR treatment was associated with significant decrease in HAM-D (df = 1,28; female [F] = 39; P = 0.001) and HAM-A scores (df = 1,28; F = 55; P = 0.001). The AMDD group showed increased amygdala-cortical connectivity (P < 0.05 [clusterwise corrected]) at week 2, which was maintained at week 8. At week 8, additional areas showed increased connectivity including insula and putamen. At 8 weeks, decrease in HAM-D scores correlated with increase in amygdala-mid cingulate and amygdala-cuneus connectivity (P = 0.05 [clusterwise corrected]). Decrease in HAM-A scores correlated with increase in amygdala-cuneus and parietal cortex connectivity (P = 0.05 [clusterwise corrected]).. Small sample-size, open-label single-arm design, HC only tested at baseline, focused only on amygdala.. Quetiapine XR effects in the treatment of AMDD are associated with modulation of amygdala connectivity.

Topics: Adult; Aftercare; Amygdala; Antipsychotic Agents; Anxiety Disorders; Cerebral Cortex; Comorbidity; Delayed-Action Preparations; Depressive Disorder, Major; Female; Humans; Magnetic Resonance Imaging; Male; Nerve Net; Quetiapine Fumarate; Treatment Outcome; Young Adult

This study investigated the dosing patterns of quetiapine augmentation (QA) for major depressive disorder (MDD) in routine practice. Between 1 January 2009 and 31 May 2013, patients with a diagnosis of MDD who were receiving QA in conjunction with an ongoing antidepressant were recruited into this study. The electronic medical records and clinical data for a total of 977 patients were reviewed up to a year. Almost half the patients maintained QA treatment for more than 3 months. The mean duration of QA was ∼6 months, and the mean initial and maintenance doses were 23.6 and 40.7 mg/day, respectively (range=12.5-400 mg/day). The most frequent adverse events observed were somnolence, followed by dry mouth and lethargy. Our results indicate that the actual doses of QA for MDD in routine practice should be lower than the doses used in placebo-controlled clinical trials and those recommended by a regulatory agency. Adequately powered and well-controlled prospective studies are needed to better understand the exact role of low doses of QA in the treatment of MDD, particularly in routine practice.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Dosage Calculations; Drug Therapy, Combination; Electronic Health Records; Female; Humans; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quetiapine Fumarate; Retrospective Studies; Time Factors; Treatment Outcome

These guidelines for the treatment of unipolar depressive disorders systematically review available evidence pertaining to the biological treatment of patients with major depression and produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians assessing and treating patients with these conditions. The relevant data have been extracted primarily from various treatment guidelines and panels for depressive disorders, as well as from meta-analyses/reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into five levels of evidence (CE A-F) and five levels of recommendation grades (RG 1-5). This second part of the WFSBP guidelines on depressive disorders covers the management of the maintenance phase treatment, and is primarily concerned with the biological treatment (including pharmacological and hormonal medications, electroconvulsive therapy and other brain stimulation treatments) of adults and also, albeit to a lesser extent, children, adolescents and older adults.

Topics: Antidepressive Agents; Antipsychotic Agents; Biological Psychiatry; Carbamazepine; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Electroconvulsive Therapy; Evidence-Based Medicine; Humans; Lithium; Plant Extracts; Psychotherapy; Quetiapine Fumarate

Topics: Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Dyslipidemias; Humans; Hyperglycemia; Quetiapine Fumarate; Weight Gain

The hypothalamic-pituitary-adrenocortical (HPA) system is believed to play an important role in the pathophysiology of major depressive disorder. In this context, the atypical antipsychotic quetiapine (QUE) has been shown to inhibit HPA system activity in healthy subjects. In this study we investigated whether the putative inhibitory effects of QUE on HPA system activity may contribute to its antidepressant efficacy. We analyzed the effects of QUE as an augmentation to the selective serotonin reuptake inhibitor (SSRI) escitalopram (ESC) on HPA system activity in comparison to a monotherapy with ESC in relation to the antidepressant effectiveness. HPA axis activity (cortisol and ACTH) was measured by means of the dexamethasone/corticotropin-releasing hormone (DEX/CRH) test which was performed before (week 0) and during (week 1, week 5) antidepressant psychopharmacotherapy. The combination therapy, but not the ESC monotherapy showed significantly inhibiting effects on HPA system activity leading to stepwise down-regulation. ACTH concentrations were reduced in the ESC/QUE group during five weeks of treatment. The inhibitory effect of QUE maybe involved in its antidepressant effects as an augmentation strategy.

Topics: Adrenocorticotropic Hormone; Adult; Antidepressive Agents; Area Under Curve; Citalopram; Corticotropin-Releasing Hormone; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

To prospectively analyze effects of extended release quetiapine fumarate (quetiapine XR) on suicidality in major depressive disorder (MDD).. Data were pooled from randomized, acute studies (4 monotherapy; 2 adjunct therapy) in adult patients with a DSM-IV diagnosis of MDD who were considered not to be at high risk of suicide at baseline and were receiving quetiapine XR 50 mg/d (n = 181), 150 mg/d (n = 910), or 300 mg/d (n = 685) or placebo (n = 957). Data from 1 acute monotherapy study in elderly patients receiving quetiapine XR (50-300 mg/d; n = 166) or placebo (n = 172) and maintenance data (up to 52 weeks) for patients receiving quetiapine XR (50-300 mg/d; n = 391) or placebo (n = 385) were also evaluated. Overall incidences and relative risks for suicidality (suicidal behavior/ideation) were assessed by Columbia-type review and classification. The proportion of patients with Montgomery-Asberg Depression Rating Scale (MADRS) item 10 (suicidal thoughts) score ≥ 4 was analyzed.. Incidence of suicidality during acute treatment in adults was 1.1%, 0.7%, 0.7%, and 0.7% with quetiapine XR 50 mg/d, 150 mg/d, and 300 mg/d and placebo, respectively. The proportion of patients with MADRS item 10 score ≥ 4 during acute treatment in adults was 1.8% with quetiapine XR (all doses combined) and 2.4% with placebo. In elderly patients, the incidence of suicidality during acute treatment was 0.6% in both treatment groups; the proportion of patients with MADRS item 10 score ≥ 4 was 0% with quetiapine XR (all doses combined) and 1.2% with placebo. During maintenance treatment, the incidence of suicidality was 0.3% (n = 1) and 0.5% (n = 2) for quetiapine XR and placebo, respectively. The proportion of patients with MADRS item 10 score ≥ 4 was 4.1% with quetiapine XR in the open-label stabilization period and 0.3% with quetiapine XR and 0.5% with placebo during the randomized period.. This analysis suggests that there is no evidence of treatment-emergent suicidality with quetiapine XR therapy in patients with MDD considered not to be at high suicide risk at baseline.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Suicide; Treatment Outcome; Young Adult

Major depressive disorder is the most common mood disorder in the United States and European Union; however, the limitations of clinically available antidepressant drugs have led researchers to pursue novel pharmacological treatments. Clinical studies have reported that monotherapy with the atypical antipsychotic drug quetiapine produces a rapid reduction in depressive symptoms that is apparent after 1 week of treatment, and it is possible that the active metabolite N-desalkylquetiapine, which structurally resembles an antidepressant drug, produces antidepressant effects. Neuropharmacological evaluations of the neurotensin NTS1 receptor agonist PD149163 suggest antidepressant efficacy, but the effects of a NTS₁ receptor agonist in an antidepressant animal model have yet to be reported. The present study examined the antidepressant-like effects of N-desalkylquetiapine, PD14916, quetiapine, the tricyclic antidepressant drug imipramine, the atypical antipsychotic drug risperidone, and the typical antipsychotic drug raclopride on responding in male Sprague-Dawley rats trained on a differential-reinforcement-of-low-rate 72-s operant schedule, a procedure used for screening antidepressant drugs. Quetiapine, PD149163, risperidone, and imipramine exhibited antidepressant-like effects by increasing the number of reinforcers earned, decreasing the number of responses emitted, and shifting the interresponse time (IRT) distributions to the right. N-Desalkylquetiapine produced a partial antidepressant-like effect by decreasing the number of responses emitted and producing a rightward shift in the IRT distributions, but it did not significantly alter the number of reinforcers earned. Raclopride decreased reinforcers and responses. These data suggest that N-desalkylquetiapine likely contributes to quetiapine's antidepressant efficacy and identify NTS₁ receptor activation as a potential novel pharmacologic strategy for antidepressant drugs.

Topics: Alkylation; Animals; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Behavior, Animal; Conditioning, Operant; Depressive Disorder, Major; Dibenzothiazepines; Disease Models, Animal; Male; Neurotensin; Quetiapine Fumarate; Rats, Sprague-Dawley; Receptors, Neurotensin; Reinforcement, Psychology

Previous studies suggested that antidepressants augmented with second-generation antipsychotics (SGAs), including aripiprazole, olanzapine, quetiapine, and risperidone, resulted in better treatment response or higher rates of remission in patients with major depressive disorder (MDD). However, population-based study on SGA augmentation for patients with MDD remains limited. The purpose of this study was to investigate the effectiveness of SGA augmentation for treatment of MDD using the National Health Insurance Research Database in Taiwan.. The subjects were patients with MDD (ICD-9-CM code: 296.2 and 296.3) who were initially admitted to psychiatric inpatient settings for the first time between January 1, 1996, and December 31, 2007, and could be tracked until December 31, 2011. To assess the treatment effect of SGA augmentation, 993 MDD patients who received aripiprazole, olanzapine, quetiapine, or risperidone augmentation treatment for 8 weeks or more were included in this 1-year mirror-image study. Outcome measures included length of psychiatric hospitalization and number of psychiatric admissions and emergency room (ER) visits.. After patients received SGA augmentation treatment, key psychiatric service use (including length of psychiatric hospitalization [P < .0001], number of psychiatric admissions [P < .0001], and ER visits [P = .0006]) due to MDD diagnosis was significantly reduced. Subgrouping analysis for each SGA drug also showed significant reduction in number of psychiatric admissions for MDD patients who received aripiprazole (P < .0001), olanzapine (P = .003), quetiapine (P < .0001), and risperidone (P < .0001).. The study provides support that aripiprazole, olanzapine, quetiapine, and risperidone augmentation therapy could be effective in reducing psychiatric service utilization among MDD patients.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Dibenzothiazepines; Drug Synergism; Drug Therapy, Combination; Emergency Service, Hospital; Female; Hospitalization; Humans; Male; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Taiwan; Treatment Outcome

Quetiapine has been recently approved as an add-on therapy in the treatment of major depressive disorders in the case of inadequate response to antidepressant monotherapy. Thereby the antidepressant potential is attributed to the N-demethylated metabolite norquetiapine (NQ). The aim of this cross-sectional analysis was to relate quetiapine (Q) doses to serum concentrations of Q and its active metabolite and clinical effects.. Data were obtained from patients who had been treated with different antidepressants and augmented under naturalistic conditions with Q for whom blood level measurements were requested.. For this analysis, 105 depressed patients were included who had been augmented with Q. The mean daily doses of Q were 222 ± 125 mg. Doses correlated significantly (P < 0.001) with the highly variable serum concentrations of both Q and NQ. Median serum concentrations of Q and NQ were 46 ng/mL (25th to 75th percentile 20-91 ng/mL) and 59 ng/mL (25th to 75th percentile 26-133 ng/mL), respectively. Concentrations per dose ranged from 0.10 to 0.58 ng·ml·mg for Q and from 0.17 to 0.59 ng·ml·mg for NQ. Most patients (55%) received comedications in addition to the antidepressant drug and Q. According to the clinical global impressions scale, 60% of the patients were either much (36%) or very much improved (24%). Receiver-operating characteristic analysis revealed no significant differences of serum concentrations between responders and nonresponders for NQ (P = 0.835) but a trend for Q (P = 0.056).. Due to marked variability of Q and NQ concentrations in the blood, therapeutic drug monitoring may be helpful to identify pharmacokinetic peculiarities. The lack of correlation between serum concentrations of NQ and clinical improvement casts doubts on the concept that NQ is the pharmacologically active principle for the augmentation therapy.

Topics: Antidepressive Agents; Antipsychotic Agents; Cross-Sectional Studies; Depressive Disorder, Major; Dibenzothiazepines; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies

Standard clinical trial methodology in depression does not allow for careful examination of early changes in symptom intensity. The purpose of this study was to use daily "Mental Health Telemetry" (MHT) to prospectively record change in depressive and anxiety symptoms for depressed patients receiving augmentation treatment, and determine the extent and predictive capacity of early changes. We report results of a 6-week, open-label study of the addition of quetiapine XR (range, 50-300 mg) for adult patients (n = 26) with major depressive disorder who were nonresponsive to antidepressant treatment. In addition to regular study visits, all participants completed daily, wirelessly transmitted self-report ratings of symptoms on a Smartphone. Daily and 3-day moving average mean scores were calculated, and associations between early symptom change and eventual response to treatment were determined. Improvement in depressive and anxiety symptoms was identified as early as day 1 of treatment. Of the total decline in depression severity over 6 weeks, 9% was present at day 1, 28% at day 2, 39% at days 3 and 4, 65% at day 7, and 80% at day 10. Self-report rating of early improvement (≥20%) in depressive symptoms at day 7 significantly predicted responder status at week 6 (P = 0.03). Clinician-rated depressive and anxiety symptoms only became significantly associated with responder status at day 14. In conclusion, very early changes in depressive symptoms were identified using MHT, early changes accounted for most of total change, and MHT-recorded improvement as early as day 7 significantly predicted response to treatment at study end point.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Quetiapine Fumarate; Severity of Illness Index; Telemetry; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to investigate the dosing patterns of adjunctive quetiapine or adjunctive aripiprazole in the treatment of major depressive disorder from 2006 to 2010, and to evaluate the impact of Food and Drug Administration (FDA) approval on these dosing patterns. Patients included in the study were adults diagnosed with major depressive disorder, and treated with adjunctive aripiprazole or quetiapine between the years 2006 and 2010. The average daily dose and dose distribution were calculated and assessed statistically over the same time period. The mean daily dose for patients treated with adjunctive aripiprazole decreased from 13.5 mg/day in 2006 to 6.9 mg/day in 2010, whereas the mean daily dose for patients treated with quetiapine increased from 129 mg/day in 2006 to 139 mg/day in 2007, decreasing to 123 mg/day in 2010. The proportion of patients receiving FDA-recommended doses increased significantly for aripiprazole (86.3% in 2006 to 94.5% in 2010; P<0.001) and remained relatively stable for quetiapine (21.3% in 2006 to 24.0% in 2010; NS). The majority of patients treated with quetiapine received doses below those recommended by the FDA throughout the study period. Aripiprazole was mostly prescribed at therapeutic doses (pre-FDA and post-FDA approval), although the mean dose decreased significantly over time.

Topics: Adolescent; Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Cohort Studies; Depressive Disorder, Major; Dibenzothiazepines; Drug Approval; Drug Prescriptions; Drug Therapy, Combination; Drugs, Investigational; Female; Humans; Insurance, Pharmaceutical Services; Male; Middle Aged; Piperazines; Practice Patterns, Physicians'; Quetiapine Fumarate; Quinolones; Retrospective Studies; Spatio-Temporal Analysis; United States; United States Food and Drug Administration; Young Adult

Electroconvulsive therapy (ECT) is especially necessary to revert some types of depressive disease; nevertheless, it has some widely recognized adverse effects, such as short-term memory loss. Moreover, some articles have reported its potential association with falls; this literature is, however, scanty and mainly consists of case reports. We present the case of a man who has a diagnosis of neurally mediated syncope at the age of 79 years, during the maintenance ECT. The patient had a significant increase in syncope frequency in the period he was treated with ECT, followed by a dramatic decrease when ECT was discontinued.

Topics: Aged; Antipsychotic Agents; Baroreflex; Depressive Disorder, Major; Dibenzothiazepines; Electroconvulsive Therapy; Humans; Male; Mitral Valve Insufficiency; Quetiapine Fumarate; Syncope; Unconsciousness; Urination

While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown.. To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy.. Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources.. With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine.. Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine.

Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cost-Benefit Analysis; Decision Support Techniques; Depressive Disorder, Major; Dibenzothiazepines; Drug Combinations; Drug Costs; Drug Resistance; Fluoxetine; Health Care Costs; Humans; Piperazines; Quetiapine Fumarate; Quinolones

A patient's death due to severe hematologic adverse effects of the concomitant use of four psychotropic medications is reported.. A 40-year-old Caucasian woman with a 9-year history of depression and anxiety (managed with alprazolam) was admitted to a psychiatric hospital for the treatment of acute psychotic symptoms. After nine days, the patient was discharged home on a regimen of lamotrigine, mirtazapine, quetiapine, and venlafaxine. Five weeks later, the development of severe ocular cellulitis, severe oral thrush, and febrile neutropenia necessitated the woman's urgent rehospitalization; on admission, her white blood cell count was 600 cells/mm(3), her absolute neutrophil count was 18 cells/mm(3), and microbial pathogens were isolated in peripheral blood and tracheal aspirate cultures. Despite treatment with antibiotics and filgrastim, the patient developed multiorgan dysfunction and died five days later from septic shock. The woman's concomitant use of multiple psychotropics and the late recognition of drug-induced agranulocytosis likely contributed to her severe symptoms and ultimate death. The application of the Naranjo scale to this case yielded a score of 6, indicating a probable adverse drug reaction. Although hematologic adverse effects have been reported with the use of each of the four drugs implicated in the woman's death, this is thought to be the first report of fatal agranulocytosis associated with any of the drugs.. A 40-year old woman with a history of acute psychotic symptoms developed agranulocytosis and neutropenia after starting therapy that included lamotrigine, mirtazapine, quetiapine, and venlafaxine.

Topics: Adult; Agranulocytosis; Antidepressive Agents, Second-Generation; Antimanic Agents; Antipsychotic Agents; Blood Cell Count; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Fatal Outcome; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lamotrigine; Mianserin; Mirtazapine; Multiple Organ Failure; Neutropenia; Orbital Cellulitis; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Recombinant Proteins; Shock, Septic; Triazines; Venlafaxine Hydrochloride

Electroconvulsive therapy cannot proceed safely unless blood pressure is within the reference range. Finding the cause of very high or low blood pressure can be very difficult, time consuming, and expensive. We suggest a more valid and reliable time to check blood pressure. This is highlighted in the case of a man that became riddled with iatrogenic complications and needless treatments.

Topics: Aged; Anesthesia; Antiparkinson Agents; Antipsychotic Agents; Blood Pressure; Depressive Disorder, Major; Dibenzothiazepines; Electroconvulsive Therapy; Humans; Hypertension; Iatrogenic Disease; Male; Parkinson Disease; Quetiapine Fumarate; Recurrence

There exists a growing argument in favour of a more dimensional approach to the diagnosis and treatment of psychiatric patients. This encompasses first the idea of a spectrum of symptoms correlating to severity within a single disorder, and secondly, the idea of spectra of different disorders sharing overlapping collections of symptoms. Here we consider the issue in light of specific clinical examples we have observed, which support the idea of a 'mental illness spectrum', both with symptoms within a single disorder, and between different mental disorders.

Topics: Antipsychotic Agents; Bipolar Disorder; Borderline Personality Disorder; Combined Modality Therapy; Comorbidity; Depressive Disorder, Major; Diagnosis, Differential; Dibenzothiazepines; Humans; International Classification of Diseases; Mental Disorders; Prodromal Symptoms; Psychotherapy; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Adolescent; Anorexia Nervosa; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Diagnosis, Differential; Dibenzothiazepines; Duloxetine Hydrochloride; Electrocardiography; Female; Humans; Hypokalemia; Quetiapine Fumarate; Suicide, Attempted; Thiophenes; Unconsciousness

To compare health care utilization and expenditures in patients with depression whose initial antidepressant (AD) treatment was augmented with a second-generation antipsychotic.. Claims data from January 1, 2001, through June 30, 2009, were used to select patients aged 18 to 64 years with depression treated with ADs augmented with aripiprazole, olanzapine, or quetiapine. Patients were required to have 6 months of continuous eligibility before the first AD prescription and 6 months after the second-generation antipsychotic augmentation (index) date. Utilization and expenditures were assessed for 6 months after the index date. Multivariate regression was used to estimate adjusted expenditures and risks for hospitalizations and emergency department visits.. A total of 483 patients treated with aripiprazole, 978 with olanzapine, and 2471 with quetiapine were selected. Mean adjusted expenditures for aripiprazole were significantly lower than those for olanzapine for each service category (all-cause, all-cause medical care, mental health-related, and mental health-related medical care) and were significantly lower than those for quetiapine for each category with the exception of mental health-related. The adjusted risks for hospitalization and emergency department visits were significantly higher for quetiapine than for aripiprazole.. Compared with patients treated with ADs and aripiprazole, those treated with ADs and olanzapine or quetiapine had greater utilization and higher expenditures.

Topics: Adolescent; Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Data Interpretation, Statistical; Databases, Factual; Depressive Disorder, Major; Dibenzothiazepines; Drug Costs; Drug Therapy, Combination; Drug Utilization Review; Female; Health Expenditures; Humans; Insurance Claim Review; Male; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Young Adult

Topics: Antidepressive Agents; Antipsychotic Agents; Combined Modality Therapy; Depressive Disorder, Major; Dibenzothiazepines; Duloxetine Hydrochloride; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Suicidal Ideation; Thiophenes; Treatment Outcome

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Drug Approval; Drug Therapy, Combination; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; United States; United States Food and Drug Administration

To identify the factors associated with newly prescribed, first-line, second-generation antipsychotics (SgAs) associated with weight gain-olanzapine, risperidone, and quetiapine.. Retrospective medical record review.. Outpatient and inpatient psychiatry services at a tertiary care, academic medical center.. Three hundred forty consecutive adults who had major depressive disorder with psychotic features, bipolar I, bipolar II, bipolar not otherwise specified, or schizoaffective disorder over two time periods (August 30-October 30, 2009, and April 1-May 31, 2010).. Clinical and sociodemographic variables associated with newly prescribed olanzapine, risperidone, and quetiapine were identified by using univariate and multivariate logistic regression. Several clinical factors were individually associated with initiation of these SgAs: mania (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.2-10.8, p=0.02), psychosis (OR 3.3, 95% CI 1.5-6.9, p=0.002), and inpatient treatment (OR 3.8, 95% CI 1.8-7.9, p=0.0005). Prevalent use of lithium (OR 0.3, 95% CI 0.1-0.9, p=0.03) and being married (OR 0.3, 95% CI 0.1-0.8, p=0.02) were inversely associated with new use of an SgA. Mania, psychosis, married status, and lithium use remained independently associated on multivariate analysis. Factors related to metabolic or vascular risk were not associated with SgA initiation.. Psychiatric clinicians were influenced heavily by clinical features related to mental status and acuity when determining whether to prescribe SgAs. However, factors related to vascular risk were not associated. Future observational studies should consider current clinical status as an important factor in determining propensity to receive antipsychotics or other short-term treatments for bipolar and related disorders.

Topics: Academic Medical Centers; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

PTSD is a complex disorder, which frequently occurs in comorbidity with anxious disorder, personality disorder, addiction or substance abuse disorder, depressive disorder with or without psychotic symptoms and psychotic disorder. PTSD symptoms may result from deregulation of several different neurotransmitter systems. Pharmacotherapy of PTSD depends on clinical features and the presence of comorbid disorders. Pharmacotherapy of PTSD involves use of anxiolytics, adrenergic receptor antagonists, antidepressants, anticonvulsants and novel antipsychotics. Serotoninergic effect of antidepressants is not only effective in treating depression, but also appears to be helpful in PTSD treatment, particularly in reduction of intrusive symptoms, emotional reactivity, impulsiveness, aggression and suicidal ideation. Anypsychotics with serotoninergic-dopaminergic antagonism are being prescribed often in treatment of psychotic depression, while in PTSD treatment they are proved to be efficient in relieving intrusive symptoms and nightmares. Quetiapine as serotoninergic-dopaminergic antagonist is efficient in treatment of chronic insomnia as well as in reduction of aggressiveness. Considering PTSD refractoriness to therapy, high incidence of comorbidity and significant functional impairment, it is important to search for new psychopharmacological combinations in order to improve mental status of the patient. The paper presents 46 years old male patient with the diagnosis of Enduring personality changes following war PTSD (F62.0) in comorbidity with Recurrent depressive disorder with psychotic symptoms (F33.3), who was treated with combination of venlafaxine and quetiapine.

Topics: Affective Disorders, Psychotic; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Combat Disorders; Comorbidity; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Middle Aged; Personality Disorders; Quetiapine Fumarate; Secondary Prevention; Stress Disorders, Post-Traumatic; Venlafaxine Hydrochloride; Veterans

Topics: Adolescent; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Thrombocytopenia

The Numbers of elderly people are gradually increasing in our society, and mood disorders are progressively increasing among older people. Old age depression may also occur after life events: the death of the significant other, economical reasons, health problems (neurological and/or cardiovascular diseases, arthritis, cancer, nutritional deficiency) and can develop into a depressive state. Old age depression is often mistreated, or undertreated, and also underdiagnosed, and this for several reasons: older people reduce their social relations, depression very often presents as a comorbidity with organic diseases (that cover and mask depressive symptoms); finally,the patient may believe that a depressive state is a normal course of life in older people. Recovering from depression is really feasible both in young/adults and in old people, but in older people we can find a higher frequency of admission to hospital, or mortality or suicidality. The depressive symptoms in old age depression is similar to those in adults, however the following aspects require special care, in order to ensure a correct diagnosis despite the presence of comorbidities: - the mood: in contrast with the young and adult, old people often do not complain about their low mood; - the psychotic simptoms: hypocondriacal and psychotic, including hallucinatory symptoms are often present; - the anxiety symptoms: these are often present together with neuro-sensory symptoms; - the somatic symptoms: the comorbidity with organic diseases can mask and overlap the depressive state; - reduction of congnitive functioning: in these cases, which are quite frequent, it is essential to make a differential diagnosis from "pseudodementia" and "dementia". In conclusion, several factors contribute to the onset of depression in old age, so that we can assert that it is a really a multifactorial disease.

Topics: Aged; Alzheimer Disease; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Comorbidity; Dementia, Vascular; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Humans; Life Change Events; Psychomotor Agitation; Quetiapine Fumarate; Risk Factors; Selective Serotonin Reuptake Inhibitors

Topics: Antipsychotic Agents; Anxiety Disorders; Death, Sudden, Cardiac; Depressive Disorder, Major; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Metabolic Syndrome; Quetiapine Fumarate; Risk Factors; United States; United States Food and Drug Administration; Weight Gain

Topics: Antipsychotic Agents; Anxiety Disorders; Depressive Disorder, Major; Dibenzothiazepines; Drug Approval; Humans; Quetiapine Fumarate; United States; United States Food and Drug Administration

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Humans; National Institute of Mental Health (U.S.); Quetiapine Fumarate; Randomized Controlled Trials as Topic; Regression Analysis; Research Support as Topic; United States

Research on postpartum mood disorders has focused primarily on major depressive disorder, bipolar I disorder, and puerperal psychosis and has largely ignored or neglected bipolar II disorder. Hypomanic symptoms are common after delivery but frequently unrecognized. DSM-IV does not consider early postpartum hypomania as a significant diagnostic feature. Although postpartum hypomania may not cause marked impairment in social or occupational functioning, it is often associated with subsequent, often disabling depression. Preliminary evidence suggests that bipolar II depression arising in the postpartum period is often misdiagnosed as unipolar major depressive disorder. The consequences of the misdiagnosis can be particularly serious because of delayed initiation of appropriate treatment and the inappropriate prescription of antidepressants. Moreover, no pharmacological or psychotherapeutic studies of bipolar postpartum depression are available to guide clinical decision making. Also lacking are screening instruments designed specifically for use before or after delivery in women with suspected bipolar depression. It is recommended that the treatment of postpartum bipolar depression follow the same guidelines as the treatment of nonpuerperal bipolar II depression, using medications that are compatible with lactation.

Topics: Adult; Anticonvulsants; Antidepressive Agents; Bipolar Disorder; Breast Feeding; Depression, Postpartum; Depressive Disorder, Major; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Lactation; Lithium Compounds; Mass Screening; Milk, Human; Pregnancy; Pregnancy Complications; Psychiatric Status Rating Scales; Quetiapine Fumarate; Surveys and Questionnaires

Psychomotor retardation (PR) is among the most important features of depression. This study investigates the development of day- and night-time as well as intensity and quantity of circadian motor activity during a 4-week course of treatment among 27 patients with depression compared to 27 healthy controls. A diagnosis of major depression was made using SCID. Motor activity was continuously measured with an actigraph during the study and clinical course of depression with HAM-D-21. Motor activity was described as the quantity and intensity of movements during day- and night- time. Clinically improved patients had significantly intensified movements after 4 weeks, compared to subjects with <50% improvement on HAM-D. While the measures of day-time level of movements captured the clinical improvement of depression, clinical improvement was not reflected by the night-time measurements. This study demonstrates that the separated analysis of level and quantity of movements supports a better understanding of the nature of psychomotor retardation during depression. The subdivision in day- and night-time activity objectively measured with actigraphy captures distinct patterns of motor activity and represents prognostic factors in the treatment outcome of depression. The study also highlights the importance of studying the intensity of movements separately from the quantity of movements in relation to treatment outcome.

Topics: Actigraphy; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Circadian Rhythm; Citalopram; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Longitudinal Studies; Male; Middle Aged; Motor Activity; Personality Inventory; Prognosis; Prospective Studies; Quetiapine Fumarate; Signal Processing, Computer-Assisted; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Venlafaxine Hydrochloride

We encountered 2 patients with a psychiatric disorder (depression in one and catatonia in one) accompanied by motor inhibition that was complicated by pulmonary embolism (PE). In both cases, the psychiatric disorder was safely resolved with electroconvulsive therapy (ECT) during anticoagulant therapy. The 2 cases direct our attention to at least 3 important points regarding safe administration of ECT shortly after the occurrence of PE, that is, careful evaluation of cardiac function and residual deep vein thrombosis before the start of an ECT course, adjustment of anticoagulants, and prevention of recurrent deep vein thrombosis and PE by methods in addition to anticoagulant therapy (fluid infusion, use of support hose, and timely ECT).

Topics: Aged; Anticoagulants; Antipsychotic Agents; Catatonia; Depressive Disorder, Major; Dibenzothiazepines; Electroconvulsive Therapy; Female; Fluid Therapy; Heart Function Tests; Humans; Hypochondriasis; Lithiasis; Middle Aged; Pulmonary Embolism; Quetiapine Fumarate; Recurrence; Venous Thrombosis

We present a case of massive overdose with the atypical antipsychotic quetiapine in a 34-year-old woman (body weight 65 kg). At admission, approximately 2 to 4 hours after ingestion of approximately 24 g of quetiapine, the patient was comatose (Glasgow Coma Scale score 5), requiring orotracheal intubation and transfer to the intensive care unit. Because of myoclonic jerks and generalized seizures, benzodiazepines were administered. In addition to transient mild hypotension after intubation, the main cardiovascular manifestation was sinus tachycardia. The QT interval was normal, and the QTc interval (Bazett's correction) was maximally prolonged to 620 ms. However, no malignant arrhythmias were observed. The patient recovered within 2 days but remained agitated and aggressive, for which she was transferred to the psychiatric clinic. The pharmacokinetics of quetiapine in such a large overdose could not be described by simple first-order kinetics. The initially observed rapid decline of the plasma concentrations of quetiapine could be simulated by first-order kinetics (half life = 4.1 hr) and can most probably be explained by rapid distribution into tissues. The final elimination of the drug from the body occurred after approximately 34 hours at much slower rate, most probably reflecting redistribution from tissues into blood and consecutive hepatic clearance of the drug.

Topics: Adult; Antipsychotic Agents; Autonomic Nervous System Diseases; Chromatography, High Pressure Liquid; Coma; Depressive Disorder, Major; Dibenzothiazepines; Drug Overdose; Female; Glasgow Coma Scale; Half-Life; Humans; Long QT Syndrome; Parasympathetic Nervous System; Quetiapine Fumarate; Schizophrenia; Seizures; Suicide, Attempted

Electroconvulsive therapy (ECT) is indicated for the treatment of severe treatment refractory depression in many countries. It is associated with a low risk of morbidity and mortality. It is usual for high doses of psychotropic medications to be prescribed concomitantly with ECT, although published data on the interactions of these with ECT is lacking. Here, we present the case of a middle-aged woman on multiple psychotropic medications who went into status epilepticus for 45 minutes after ECT.

Topics: Affect; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antimanic Agents; Antipsychotic Agents; Clomipramine; Combined Modality Therapy; Depressive Disorder, Major; Dibenzothiazepines; Electroconvulsive Therapy; Electroencephalography; Female; Humans; Lithium Compounds; Middle Aged; Quetiapine Fumarate; Recurrence; Status Epilepticus; Thyroxine; Tryptophan

Clinical trials suggest between 30-50% of depressed patients have an inadequate outcome to antidepressant pharmacotherapy. Among the approaches to improve outcome has been augmentation with antipsychotic medications. We aim to investigate the efficacy and tolerability of augmentation with quetiapine in depressed patients with a partial response to antidepressants.. Patients with a Major Depressive Disorder (DSMIV) who had partial/no response to a stable dose of an Selective Serotonin Reuptake Inhibitors (SSRI)/SNRI were recruited. All patients received add-on quetiapine (200-600 mg nocte) in a 6-week trial. Outcome measures (HAMD, MADRS) were assessed at screening, baseline, weeks 1, 2, 4 and 6. Extrapyramidal symptoms (EPSEs) were assessed at baseline, weeks 2, 4 and 6. A neuropsychological battery of tests was administered at baseline, weeks 3 and 6.. Nineteen patients entered the trial and 18 completed the trial per protocol. We report a rapid improvement in depression ratings over 6 weeks (p < 0.0005) and remission rates of 67% at week 1 and 94% at week 6. There was no evidence of EPSE and no worsening (and some improvement) of cognition.. This suggests clinical benefits of quetiapine augmentation of SSRI/SNRI antidepressants with no worsening, and possible improvements in cognition.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Cognition; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Remission Induction; Selective Serotonin Reuptake Inhibitors; Young Adult

Severe paradoxical insomnia, documented by actigraphy, was the predominant presenting complaint of a 48-year-old woman subsequently diagnosed with major depression. Both disorders remitted following a course of 5 electroconvulsive therapy treatments in spite of being previously refractory to hypnotic and antidepressant pharmacotherapy.

Topics: Combined Modality Therapy; Cyclohexanols; Depressive Disorder, Major; Diagnosis, Differential; Dibenzothiazepines; Drug Therapy, Combination; Electroconvulsive Therapy; Female; Humans; Middle Aged; Quetiapine Fumarate; Sick Role; Sleep Initiation and Maintenance Disorders; Suicide; Suicide Prevention; Venlafaxine Hydrochloride

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Estrogen Replacement Therapy; Female; Humans; Hysterectomy; Menopause; Middle Aged; Postmenopause; Quetiapine Fumarate; Valproic Acid

Topics: Amphetamine-Related Disorders; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; HIV Seropositivity; Humans; Male; Middle Aged; Priapism; Quetiapine Fumarate

Massive elevations of serum creatine kinase (CK) can occur in a significant number of patients treated with neuroleptics in the absence of neuroleptic malignant syndrome (NMS). We report two cases of CK-elevations associated with quetiapine treatment, which disappeared after drug discontinuation. To our knowledge, case number one is the first case of quetiapine-induced CK elevation in a neuroleptic-naïve patient. We thus suggest CK assessment when myalgia occurs with neuroleptic treatment.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Creatine Kinase; Depressive Disorder, Major; Dibenzothiazepines; Humans; Male; Mianserin; Mirtazapine; Olanzapine; Pain; Psychotic Disorders; Quetiapine Fumarate

To report the successful treatment of phenelzine-associated insomnia with low-dose quetiapine in a patient with refractory depression.. A 42-year-old white man with severe major depression unresponsive to selective serotonin-reuptake inhibitors, bupropion, and tricyclic antidepressants improved following treatment with the monoamine oxidase inhibitor (MAOI) phenelzine. Insomnia, present to a moderate degree prior to antidepressant therapy, worsened markedly following phenelzine treatment and failed to respond to diphenhydramine, temazepam, triazolam, clonazepam, zolpidem, or trazodone given at high therapeutic doses. Sleep disturbance resolved with low-dose (50 mg) adjunctive quetiapine, with no adverse effects.. Major depression refractory to standard therapy is a common and serious condition. Some cases respond to MAOIs; however, orthostatic hypotension and insomnia frequently occur. Potentially serious MAOI interactions with psychotropic drugs have raised concerns about combining these agents. In this case, a failure of a number of other medications known to treat MAOI-associated insomnia safely prompted a trial of quetiapine. Despite the possibility that enhanced serotonergic activity might have resulted in serotonin syndrome, no adverse interactions between phenelzine and quetiapine were noted. The use of low-dose, once-daily quetiapine, along with its unique binding properties, may account for its increased safety in combination with phenelzine.. This case illustrates that low-dose quetiapine may be an alternative treatment for phenelzine-associated insomnia. Further case reports are needed to establish the safety and effectiveness of combining these agents.

Topics: Adult; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Humans; Male; Monoamine Oxidase Inhibitors; Phenelzine; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Monitoring; Female; Humans; Hypothyroidism; Middle Aged; Quetiapine Fumarate; Thyroid Hormones

Therapeutic drug monitoring (TDM) is used increasingly for managing psychiatric outpatients, where the preanalytic error risk is high. Blood samples must be collected under steady-state conditions immediately before ingestion of the morning dose or before the next injection. In order to interpret the plasma levels accurately, age, gender, ethnicity, compliance, drug dosage, renal and hepatic function and comedication incl. smoking habits and diet (esp. caffeine intake and consumption of grapefruit juice) have to be taken into account. If in doubt, aberrant plasma levels should be confirmed by a second control under optimized conditions. Pharmacogenetic testing enables the identification of abnormal metabolizers. TDM and pharmacogenetic tests are useful tools to improve pharmacotherapy by preventing dose-dependent adverse drug events, optimizing dosage during long-term treatment and identifying ultrarapid metabolizers and malcompliance.

Topics: Adverse Drug Reaction Reporting Systems; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Biological Availability; Clomipramine; Cytochrome P-450 CYP2D6; Delusions; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Genotype; Humans; Male; Mental Disorders; Metabolic Clearance Rate; Middle Aged; Pharmacogenetics; Psychotropic Drugs; Quetiapine Fumarate

Topics: Adolescent; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Self-Injurious Behavior; Sleep Wake Disorders

A 47-year-old male taxi driver experienced multiple adverse drug reactions during therapy with clomipramine (CMI) and quetiapine for major depressive disorder, after having been unsuccessfully treated with adequate doses of mirtazapine and venlafaxine. Drug serum concentrations of CMI and quetiapine were significantly increased and pharmacogenetic testing showed a poor metabolizer status for CYP2D6, low CYP3A4/5 activity and normal CYP2C19 genotype. After reduction of the CMI dose and discontinuation of quetiapine, all ADR subsided except for the increase in liver enzymes. The latter improved but did not normalize completely, even months later, possibly due to concomitant cholelithiasis.

Topics: Antidepressive Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Cholelithiasis; Clomipramine; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Depressive Disorder, Major; Dibenzothiazepines; Humans; Liver; Male; Middle Aged; Phenotype; Quetiapine Fumarate

Obsessive-compulsive disorder (OCD) is a relatively common, often chronic and disabling disorder with high rates of partial and/or absent response to standard, recommended treatments, such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapy. This article presents the cases of four patients suffering from OCD and comorbid mood or anxiety disorders, who were treated with SSRIs at adequate doses for at least 12 weeks, showing a partial response. Quetiapine treatment was added to SSRIs at a dose of 25 mg/day and titrated up to 200 mg/day. Patients were followed up for 6 months. After 12 weeks, all the patients were classified as "much improved" on the Clinical Global Impression-Improvement scale and showed a Yale-Brown Obsessive-Compulsive Scale score reduction > or =35%. After 6 months of follow-up, all the patients maintained the same level of improvement. Although quetiapine augmentation to SSRIs has shown mixed results in published controlled trials in the acute treatment (12 weeks) of patients with treatment-resistant OCD, this case series indicates that patients who benefit from this pharmacologic regimen in the acute phase tend to maintain such an improvement. Larger follow-up studies are warranted to confirm our findings.

Topics: Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Combined Modality Therapy; Comorbidity; Depressive Disorder, Major; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Psychotherapy; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Fluvoxamine; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Treatment Outcome

We report a patient with advanced Parkinson's disease (PD) who developed a recurrence of major depression with psychotic features after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Electroconvulsive therapy (ECT) dramatically improved the depression without shifting electrode position or damaging the DBS hardware. This case suggests that ECT can be a safe and effective option for severe depression in PD patients treated with STN DBS.

Topics: Antiparkinson Agents; Antipsychotic Agents; Deep Brain Stimulation; Depressive Disorder, Major; Dibenzothiazepines; Electroconvulsive Therapy; Female; Humans; Levodopa; Magnetic Resonance Imaging; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Subthalamic Nucleus

Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs.. We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine.. Coincident with a generalized seizure, the patient developed 'ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes.. Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes.

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Middle Aged; Quetiapine Fumarate; Seizures; Torsades de Pointes

Major depressive disorder (MDD) is a leading cause of disability and mortality in adolescents. Empirical evidence suggests that many adolescents with MDD do not respond or respond only partially to commonly used interventions (antidepressants, psychotherapy, or a combination of antidepressants and psychotherapy). There is preliminary data in adults that adjunctive second-generation antipsychotics may be useful in treatment-resistant depression.. The aim of this study was to obtain preliminary data regarding the safety, tolerability, and clinical usefulness of quetiapine as adjunctive therapy for adolescents (13-18 years of age) diagnosed with treatment-resistant MDD. Treatment-resistant MDD was defined as a failure to respond to an adequate dose for at least 8 weeks of a selective serotonin reuptake inhibitor (SSRI).. The medical charts of 10 adolescents (13-18 years of age) diagnosed with treatment- resistant MDD, who were treated with adjunctive quetiapine, were evaluated. Doses of preexisting antidepressants remained unchanged during the period of evaluation. Response to treatment was defined as a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved).. Seven adolescents (70%) qualified as responders to treatment with adjunctive quetiapine. The median dose of quetiapine was 200 mg (mean +/- SD = 275 +/- 190.4 mg, range; 150-800 mg). Side effects included sedation (40%) and weight gain (mean +/- SD = 4.5 +/- 7.24 pounds). There was no serious adverse event.. This case series suggests that there may be a role for adjunctive quetiapine in treatment-resistant adolescent depression. Clinical safety and efficacy trials of quetiapine in this population appear to be warranted.

Topics: Adolescent; Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Endpoint Determination; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Fluvoxamine; Humans; Olanzapine; Quetiapine Fumarate; Weight Gain

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride