quetiapine-fumarate and Anxiety-Disorders

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

To provide an overview of recently published work on anxiety, focusing on generalized anxiety disorder (GAD) and its treatment.. Self-reported anxiety symptoms were highly prevalent during the COVID-19 global pandemic in both the general population and in selected groups. There remains divided opinion about whether internet-based cognitive behavioural therapy (CBT) is noninferior to face-to-face CBT for GAD. A systematic review of drug treatment for GAD showed efficacy for selective serotonin reuptake inhibitors (SNRIs), agomelatine, and quetiapine. There may be a place for repetitive transcranial magnetic stimulation in the treatment of GAD. There was some evidence of efficacy for complementary therapies, including physical exercise, yoga, acupuncture, and Withania somnifera (ashwagandha). However, a systematic review of cannabidiol and tetrahydrocannabinol found insufficient evidence of efficacy in anxiety disorders.. Antidepressants and quetiapine show efficacy in the treatment of GAD. Internet-based psychological interventions have a place in the treatment of GAD when face-to-face treatment is inaccessible. There is increasing evidence for the use of physical exercise in the management of GAD. Some other complementary therapies, including cannabinoids, require further, methodologically sound, research.

Topics: Antidepressive Agents; Anxiety Disorders; Cognitive Behavioral Therapy; COVID-19; Humans; Quetiapine Fumarate

Anxiety disorders, including panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), agoraphobia, and specific phobia, are among the most common psychiatric disorders. Although the traditional pharmacologic treatments for anxiety included barbiturates and then benzodiazepines, the introduction of tricyclic antidepressants, followed by the selective serotonin reuptake inhibitors (SSRIs), marked a tidal shift in the treatment of anxiety. Although not approved for treatment of anxiety disorders (with the exception of trifluoperazine) there is ongoing off-label, unapproved use of both first-generation "typical" antipsychotics (FGAs) and second-generation or "atypical" antipsychotics (SGAs) for anxiety. Although there have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of these reviews focused on SGAs, primarily the use of quetiapine in GAD. Given that there is little known about the potential benefits and short-and long-term risks of using antipsychotics in anxiety, there is a need for an umbrella review of systematic reviews and meta-analyses of the use of both FGAs and SGAs in anxiety disorders. The specific aims of this study are as follows: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs) and other non-antipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects; and (3) Evaluate the short- and long-term risks and side effects of prescribing antipsychotics in anxiety disorders. The review is registered on PROSPERO (CRD42021237436). Since data extraction has not begun, there is not preliminary data to share.

Topics: Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Humans; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Systematic Reviews as Topic

Withdrawal from psychoactive medication such as quetiapine is a well-documented phenomenon. Despite the extensive use of quetiapine, there have been few studies into the presence of discontinuation symptoms. We therefore performed a systematic review of published literature for evidence of quetiapine withdrawal or symptoms associated with discontinuation.. We searched PubMed, Embase, CINAHL, Medline, Web of Science, PsycINFO for articles containing the terms 'Quetiapine' AND 'withdraw. We included 13 papers, all of which were individual case reports. The quality of the individual case reports was sub-optimal, as assessed by the CARE Case Report Guidelines. There was an association between rapid cessation of quetiapine and onset of somatic symptoms such as nausea, vomiting, agitation, restlessness, diaphoresis, irritability, anxiety, dysphoria, sleep disturbance, insomnia, tachycardia, hypertension and dizziness. Three studies also reported the onset of a withdrawal dyskinesia characterised by abnormal choreiform movements as well as confusion and speech disturbance in some cases. However, these findings were limited by the number and quality of case reports identified.. Discontinuation symptoms are an uncommon side effect of quetiapine cessation, which may have clinical implications. Clinicians should therefore be alert to the possibility of quetiapine withdrawal in individuals who present with somatic symptoms or choreiform movements. However, large prospective studies are required to clarify this association.

Topics: Anxiety Disorders; Humans; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Substance Withdrawal Syndrome

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

Some studies have indicated the efficacy of quetiapine in the treatment of generalized anxiety disorder (GAD).. The purpose of this study was to systematically review the efficacy, acceptability, and tolerability of quetiapine in adult patients with GAD.. The SCOPUS, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched in April 2015. All randomized controlled trials (RCTs) of GAD were considered to be included in this meta-analysis. All RCTs of quetiapine in GAD patients providing endpoint outcomes relevant to severity of anxiety, response rate, remission rate, overall discontinuation rate, or discontinuation rate due to adverse events were included. The version reports from suitable clinical studies were explored, and the important data were extracted. Measurement for efficacy outcomes consisted of the mean-changed scores of the rating scales for anxiety, and response rate.. A total of 2,248 randomized participants in three RCTs were included. The pooled mean-changed score of the quetiapine-treated group was greater than that of the placebo-treated group and comparable to selective serotonin reuptake inhibitors (SSRIs). Unfortunately, the response and the remission rates in only 50 and 150 mg/day of quetiapine-XR (extended-release) were better than those of the placebo. Their response and remission rates were comparable to SSRIs. The rates of pooled overall discontinuation and discontinuation due to adverse events of quetiapine-XR were greater than placebo. Only the overall discontinuation rate of quetiapine-XR at 50 and 150 mg/day and the discontinuation rate due to adverse events of quetiapine-XR at 50 mg/day were comparable to SSRIs.. Based on this meta-analysis, quetiapine-XR is efficacious in the treatment of GAD in adult patients. Despite its low acceptability and tolerability, the use of 50-150 mg/day quetiapine-XR for adult GAD patients may be considered as an alternative treatment. Further well-defined studies should be conducted to warrant these outcomes.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

To evaluate the efficacy and tolerability of quetiapine for the treatment of generalized anxiety disorder (GAD), a literature search of the Medline database was conducted from inception to May 2014. The search was not restricted by language. Keywords used in the search were quetiapine and generalized anxiety disorder or anxiety. All studies assessing the use of quetiapine as monotherapy or adjunct therapy for the primary management of GAD in adults 18-65 years of age were included in this review. The nine studies included in this review were three studies evaluating the use of quetiapine extended release (XR) as monotherapy for acute GAD treatment, one study evaluating quetiapine XR monotherapy for maintenance treatment of GAD, and five studies evaluating quetiapine (2 XR, 3 immediate release) as adjunct therapy for acute GAD treatment. Quetiapine displayed both efficacy and tolerability in all monotherapy trials evaluating its use for acute and long-term treatment of GAD. Despite some limitations to and heterogeneity among the five adjunct therapy studies, three studies showed that quetiapine resulted in statistically significant changes in the Hamilton Anxiety Rating Scale or Clinical Global Impressions-Severity of Illness Scale scores. Although future studies of longer duration with broader inclusion criteria are needed to further evaluate the benefits and risks of quetiapine for GAD, in patients failing to respond to conventional antidepressant therapy, quetiapine may be a potential treatment option. With appropriate monitoring and management of adverse effects, the potential benefits of quetiapine in patients with treatment-refractory GAD may outweigh the risks associated with its use.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Drug Monitoring; Humans; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Young Adult

Evidence-based treatment approaches for generalized anxiety disorder (GAD) comprise psychotherapy, pharmacotherapy, or a combination of the two. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, and, in certain European guidelines, pregabalin, which gained European Commission approval. Although short- and long-term efficacy have been established for these agents in controlled trials, response rates of 60-70 % are insufficient, remission rates are relatively modest, and relapse rates considerable. Moreover, questions increasingly arise regarding tolerability and side-effect profiles. As an alternative, antipsychotics have long been of interest for the treatment of anxiety disorders, but investigation had been tempered by their potential for irreversible side effects. With the improved side-effect profiles of atypical antipsychotics, these agents are increasingly being investigated across Axis I disorders. Atypical antipsychotics such as quetiapine, aripiprazole, olanzapine, and risperidone have been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and have since been used in the treatment of a range of mood and anxiety disorders. In this article, we review the efficacy and tolerability of atypical antipsychotics as adjunctive therapy and/or monotherapy for individuals with GAD, a currently off-label indication. The most evidence has accumulated for quetiapine. Findings suggest that approximately 50 % of participants tolerate the side effects, most commonly sedation and fatigue. Among this subset, those who continue treatment demonstrate significant reductions in anxiety when used as adjunctive therapy or monotherapy. The appropriateness of the use of antipsychotics in the treatment of GAD is discussed.

Topics: Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Generalization, Psychological; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Treatment Outcome

Quetiapine (Seroquel(®)) is a potent U.S. Food and Drug Administration (FDA)-approved antipsychotic agent that has been used extensively for off-label indications. The current study was performed to ascertain the efficacy of some of the most prevalent off-label uses of this agent. An extensive search of electronic databases was completed using the search terms quetiapine or Seroquel, off-label and anxiety, substance abuse, dementia, delirium, personality disorder, insomnia, and sleep. Data were predictably mixed according to the indication being examined. The strongest evidence exists for anxiety and delirium. Moderate evidence exists for quetiapine as a pharmacological intervention for insomnia, dementia, and specific personality disorders. Evidence for quetiapine as a treatment for substance abuse is limited. More data are needed to establish specific dosing regimens for off-label uses and to examine the dose relationship to metabolic side effects and extrapyramidal side effects to determine whether various off-label uses justify the risk incurred with using this powerful drug.

Topics: Antipsychotic Agents; Anxiety Disorders; Delirium; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Off-Label Use; Personality Disorders; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Treatment Outcome

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

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

Most individuals with generalized anxiety disorder (GAD) fail to achieve remission despite standard treatments. As a result, we examined the efficacy and tolerability of second-generation antipsychotics (SGAs) as (a) augmentation or (b) monotherapy for GAD. We searched MEDLINE, EMBASE, PsycINFO, the Cochrane Library, controlled trials databases, and the abstracts of scientific meetings for all trials of GAD treatment with SGAs in adults. Randomized, double-blind, parallel-group trials examining SGA augmentation and monotherapy were meta-analyzed. Five augmentation studies containing 912 adults with refractory GAD indicated that SGA augmentation was not more likely to produce clinical response or remission than placebo and was associated with an increased risk of all-cause discontinuation (relative risk [RR] = 1.43; 95% confidence interval [CI], 1.04-1.96). There was no difference in the Hamilton Anxiety Rating Scale on change from baseline or weight gain between groups. Four SGA monotherapy studies containing 1383 patients with GAD indicated that treatment with 150 mg of quetiapine was more likely to lead to a clinical response (RR = 1.31; 95% CI, 1.20-1.44), remission (RR = 1.44; 95% CI, 1.23-1.68), and a greater decrease in the Hamilton Anxiety Rating Scale score (-3.66; 95% CI, -5.13 to -2.19) than placebo. However, an increased risk of all-cause discontinuation (RR = 1.30; 95% CI, 1.09-1.54) and weight gain (2.2 lb; 95% CI, 1.16-3.24) was observed. Existing data suggest that SGAs are not superior to placebo as augmentation for refractory GAD. Quetiapine monotherapy is more efficacious than placebo for uncomplicated GAD, but issues with adverse effects and tolerability may limit its use.

Topics: Antipsychotic Agents; Anxiety Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Generalized anxiety disorder (GAD) is a common, chronic mental illness that has a significant burden on the patient's quality of life. Treatment for GAD routinely consists of monotherapy with a proven anxiolytic such as an antidepressant or benzodiazepine, but many patients do not respond fully to these drugs, and additional treatment may be needed. Therefore, we reviewed the safety and efficacy of atypical antipsychotics as adjunct therapy to standard GAD pharmacotherapy in patients deemed treatment resistant. We performed a literature search of the MEDLINE database for English-language articles published from January 1966-May 2009. Identified articles were evaluated, and only open-label trials and randomized controlled trials (RCTs) were included in the review. Relevant references from the articles were also evaluated. Only a few reports of large-scale RCTs that assessed an atypical antipsychotic for treatment-resistant GAD have been published. Articles were found for five of the eight currently available atypical antipsychotics, but not for asenapine, clozapine, and paliperidone. Several open-label trials and smaller RCTs support the need for further evaluation of aripiprazole and quetiapine for treatment-refractory GAD, although one quetiapine trial demonstrated negative results. There is disparate data for risperidone, with one open-label trial and one small RCT showing positive results and one large RCT showing negative results. One open-label trial of ziprasidone and one RCT of olanzapine both showed beneficial effects of the drugs. Adverse effects were specific to each agent, with weight gain being the most common, but many studies did not monitor systematically for lipid level, weight, or glucose level changes. Although data suggest efficacy regarding the use of atypical antipsychotics for augmentation of treatment-refractory GAD, more rigorous studies (large, double-blind, placebo-controlled trials) on the safety and efficacy of these agents are needed in order to recommend their use in patients with GAD.

Topics: Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Drug Resistance; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Thiazoles

Quetiapine, an atypical antipsychotic, has been approved for the treatment of schizophrenia, acute mania, bipolar depression and unipolar major depression. However, it is often used (off-label) to treat other depressive disorders and anxiety disorders in children and adults.. This article reviews the evidence for the safety and efficacy of quetiapine in these populations, as both monotherapy and augmentation to other psychotropics.. This article provides an in-depth review of the published literature on the topic and also provides recommendations for use.. There is strong evidence to support the use of quetiapine in major depressive and generalized anxiety disorders, and preliminary support for treatment-resistant and psychotic depression. There is reasonable evidence of its benefits as an augmenting agent in obsessive-compulsive disorder, while data in other anxiety disorders are limited but promising. While long-term tolerability data are limited, quetiapine appears well tolerated in the short-term. Further randomized controlled trials are needed to confirm the efficacy and tolerability of quetiapine, both short- and long-term, in many of these conditions.

Topics: Adolescent; Adult; Antipsychotic Agents; Anxiety Disorders; Child; Comorbidity; Depressive Disorder; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Anxiety disorders are common and disabling conditions, with a lifetime prevalence of 17% in the general population. Due to high rates of treatment resistance, there is interest in new pharmacological treatment options such as second-generation antipsychotics.. To evaluate the efficacy and tolerability of second-generation antipsychotics as monotherapy or adjunctive treatment for people with anxiety disorders.. 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.. We included all randomised trials (RCTs) comparing second-generation antipsychotic drugs with placebo, benzodiazepines, pregabalin or antidepressants. Participants were people with generalised anxiety disorder, panic disorder and specific phobias including social phobia.. Two authors extracted data independently. For dichotomous data we calculated odds ratios (OR) and their 95% confidence intervals (CI). For continuous data we calculated mean differences (MD) based on a random-effects model.. The review currently includes eleven RCTs with 4144 participants on three second-generation antipsychotics (olanzapine, quetiapine, risperidone). Nine studies investigated the effects of second-generation antipsychotics in generalised anxiety disorder, only two studies investigated the effects in social phobia. There were no studies on panic disorder or any other primary anxiety disorder.Seven studies investigated the effects of quetiapine. Participants with generalised anxiety disorder responded significantly better to quetiapine than to placebo (4 RCTs, N = 2265, OR = 2.21, 95% CI 1.10 to 4.45). However, they were more likely to drop out due to adverse events, to gain weight, to suffer from sedation or to suffer from extrapyramidal side effects. When quetiapine was compared with antidepressants, there was no significant difference in efficacy-related outcomes, but more participants in the quetiapine groups dropped out due to adverse events, gained weight and feeling sedated. Only two very small studies with a total of 36 participants examined olanzapine and found no difference in response to treatment. Two trials compared adjunctive treatment with risperidone with placebo and found no difference in response to treatment.. We identified eligible trials on quetiapine, risperidone and olanzapine. The available data on olanzapine and risperidone are too limited to draw any conclusions. Monotherapy with quetiapine seems to be efficacious in reducing symptoms of generalised anxiety disorder and this effect may be similar to that of antidepressants. However, quetiapine's efficacy must be weighed against its lower tolerability.

Topics: Anti-Anxiety Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Dibenzothiazepines; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone

Atypical antipsychotic agents have a broad range of therapeutic efficacy, a relatively low incidence of causing extrapyramidal adverse effects, and a low tardive dyskinesia profile. This has led to very rapid growth in the use of these compounds as broad-spectrum psychotropic agents, and it has been reported that more than 70% of prescriptions for atypical antipsychotic medications are being used for conditions other than schizophrenia. In the area of bipolar disorder, in particular, atypical antipsychotic agents appear to positively affect illness outcome, and are considered potential first-line treatment agents. Quetiapine was approved by the US Food and Drug Administration in 1997, and is currently marketed in the US to treat schizophrenia. Aripiprazole was recently approved for the treatment of schizophrenia by the US Food and Drug Administration in late 2002, and is being used increasingly in clinical settings. Recent reports suggest that quetiapine and aripiprazole are valuable additions to the psychotropic armamentarium for the treatment of mood and anxiety disorders. Data from clinical trials and clinical reports are discussed herewith.

Topics: Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Dibenzothiazepines; Humans; Mood Disorders; Piperazines; Quetiapine Fumarate; Quinolones

Although quetiapine was introduced as an atypical antipsychotic drug with clinical efficacy in schizophrenia patients, it has been used in a variety of disease states over the last 5 years. The most common conditions have included mood and anxiety disorders, obsessive-compulsive disorder, aggression, hostility, posttraumatic stress disorder, borderline personality disorder, delirium, and comorbid substance abuse. Considering its efficacy in a wide variety of neuropsychiatric conditions and its excellent tolerability profile, quetiapine could emerge as a broad-spectrum psychotropic medication that may be helpful in psychiatry across various diagnostic categories. Traditionally, studies on the predictive validity of psychiatric disorders help with nosologic issues and controversies. Assessing quetiapine's tolerability and its overall treatment response might help tease out the predictive validity of various psychiatric syndromes (based currently on an atheoretical descriptive approach) and may shape psychiatric nosology in the future. Quetiapine's low affinity and fast dissociation from postsynaptic dopamine-2 receptors give the least risk of producing acute extrapyramidal side effects, tardive dyskinesia, and neuroleptic malignant syndrome. These factors suggest that the clinical utility of quetiapine in psychiatric conditions other than schizophrenia has not been fully exploited thus far.

Topics: Adult; Aggression; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Borderline Personality Disorder; Clinical Trials as Topic; Comorbidity; Delirium; Depressive Disorder; Dibenzothiazepines; Forecasting; Hostility; Humans; Mental Disorders; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Treatment Outcome

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

Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial.. Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS.. 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics.. Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders.. Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Comorbidity; Comparative Effectiveness Research; Female; Humans; Lithium; Male; Middle Aged; Prevalence; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome; United States

This study aims to compare treatment response in bipolar I or II depression and generalized anxiety disorder (GAD) with and without recent alcohol and/or cannabis use disorder (ALC/CAN) to quetiapine-XR (extended release) or placebo.. A randomized, double-blind, 8-week study of quetiapine-XR versus placebo in patients with bipolar I or II depression and GAD with or without a recent ALC/CAN was used to compare changes in Hamilton Depression Rating Scale-17, Hamilton Anxiety Rating Scale, the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16), Clinical Global Impression for Bipolar Disorder-Severity (CGI-BP-S), and Timeline Follow Back within and between groups.. In the quetiapine-XR group, patients with a recent ALC/CAN (n = 22) had significant decreases in QIDS-SR-16 (-9.6 ± 1.6 vs. -3.7 ± 1.7) and CGI-BP-S (-1.6 ± 0.4 vs. -0.8 ± 0.03) than those without a recent ALC/CAN (n = 24). In the placebo group, both patients with a recent ALC/CAN (n = 23) and those without (n = 21) had similar reductions in these measures. The reduction of QIDS-SR-16 scores in patients with a recent ALC/CAN was also significantly different from that of their counterparts in the placebo group. Patients who received quetiapine-XR had larger decreases in the number of drinking days/week (p = 0.17) and number of cannabis joints/week (p = 0.09) compared to those who received placebo.. Quetiapine-XR was superior to placebo in reducing QIDS-SR-16 total score in patients with a recent ALC/CAN. Patients taking quetiapine-XR used less alcohol and cannabis than patients on placebo, suggesting that quetiapine-XR may be of use in patients with bipolar disorder accompanied by GAD and other comorbidities.

Topics: Adult; Alcohol Drinking; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Cannabis; Comorbidity; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Marijuana Smoking; Middle Aged; Quetiapine Fumarate; Self Report; Treatment Outcome

This study is a pooled, post-hoc analysis evaluating once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalized anxiety disorder (GAD). Three previously reported positive, 8-week, randomized, double-blind, placebo-controlled studies evaluated quetiapine XR therapy (50, 150, 300 mg/day) in patients with GAD [Hamilton Anxiety Rating Scale (HAM-A) total score ≥ 20]. Patients were stratified by baseline severity: HAM-A total score ≥ 22, ≥ 24, < 26, ≥ 26, ≥ 28. We report HAM-A total score change, response (≥ 50% reduction in HAM-A total score), and remission (HAM-A total score ≤ 7 and ≤ 9). Quetiapine XR significantly improved HAM-A total scores compared with placebo at Weeks 1 and 8 in the HAM-A ≥ 22, ≥ 24, and ≥ 26 cohorts (all doses), at Week 1 (all doses) and Week 8 (quetiapine XR 150 mg/day) in the < 26 cohort, and at Week 1 (all doses) and Week 8 (quetiapine XR 50 and 150 mg/day) in the HAM-A ≥ 28 group (P<0.05). Week 8 effect sizes for 50, 150, and 300 mg/day were as follows: 0.29, 0.47, 0.17 (HAM-A ≥ 22); 0.35, 0.55, 0.22 (HAM-A ≥ 24); 0.18, 0.32, 0.10 (HAM-A < 26); 0.41, 0.59, 0.24 (HAM-A ≥ 26); 0.60, 0.64, 0.22 (HAM-A ≥ 28), respectively. Acute quetiapine XR monotherapy significantly improves anxiety compared with placebo in patients with moderate or severe GAD, with symptom improvements seen as early as Week 1.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Cohort Studies; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Young Adult

For many patients with generalized anxiety disorder (GAD), first-line treatment does not lead to remission. This study investigated the efficacy and tolerability of adjunctive extended-release quetiapine fumarate (quetiapine XR) in patients with GAD and an inadequate response to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).. Patients were randomized to quetiapine XR or placebo adjunctive to SSRI/SNRIs in an 11-week study. The primary endpoint was change from randomization to week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Secondary variables were HAM-A psychic/somatic clusters, response, and remission, and Clinical Global Impression–Severity of Illness (CGI-S) score.. A total of 409 patients received quetiapine XR (n=209) or placebo (n=200). The week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (–10.74; P=.079) vs placebo (–9.61). Secondary variables were generally consistent with the primary analysis, except for a significant reduction in HAM-A total score (week 1) and significant improvements in HAM-A psychic cluster and CGI-S total scores (week 8). Adverse events included dry mouth, somnolence, sedation, headache, and dizziness.. In patients with GAD and an inadequate response to SSRI/SNRIs, adjunctive quetiapine XR did not show a statistically significant effect for the primary endpoint at week 8, although some secondary endpoints were statistically significant vs placebo. Quetiapine XR was generally well tolerated.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neurotransmitter Uptake Inhibitors; Psychiatric Status Rating Scales; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

To study the efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar I or II depression with comorbid generalized anxiety disorder (GAD) and other comorbidities.. The study was conducted from January 2007 to November 2011. The Mini-International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV bipolar disorder, GAD, and other Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. The Hamilton Depression Rating Scale-17 items (HDRS-17) was used as a primary outcome to evaluate the difference between the 2 groups using the change from baseline to end of study. Last observation carried forward and mixed-effects modeling for repeated measures were used to analyze the primary and secondary outcome measures.. Of the 120 patients screened, 100 patients were randomized to receive quetiapine-XR (n = 50) or placebo (n = 50). Twenty-six patients in the quetiapine-XR and 18 in the placebo group completed the study. The mean quetiapine-XR dose was 276 ± 50 mg/d (50-300 mg/d). There was no significant difference between the 2 groups in the change from baseline to end of study in HDRS-17 total score with an effect size of 0.19 favoring quetiapine-XR. There were also no significant differences between the 2 groups in secondary efficacy and safety outcome measures.. Quetiapine-XR was not significantly superior to placebo in bipolar I or II depression with GAD and other comorbidities, suggesting that data from relatively "pure" bipolar patients may not be generalizable to a highly comorbid population.. ClinicalTrials.gov identifier: NCT00671853.

Topics: Acute Disease; Adult; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Comorbidity; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Synergism; Female; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Treatment Outcome

This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD.. Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4-8 weeks) and a 12-18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI).. In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: -0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score 'family life/home responsibilities' (-0.13 vs. 0.32; p=0.011), but not 'social life' (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score 'days lost' (-0.05 vs. 0.11; p=0.027), but not 'work/school' (-0.10 vs. 0.29; p=0.051) or 'days underproductive' (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).. Lack of active-comparator arm, exclusion of patients with comorbid depression.. In patients with GAD, long-term treatment with quetiapine XR (50-300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Humans; Middle Aged; Quetiapine Fumarate; Sleep; Young Adult

For many patients with generalized anxiety disorder (GAD), first-line treatment does not lead to remission. This study investigated the efficacy and tolerability of adjunctive extended-release quetiapine fumarate (quetiapine XR) in patients with GAD and an inadequate response to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).. Patients were randomized to quetiapine XR or placebo adjunctive to SSRI/SNRIs in an 11-week study. The primary endpoint was change from randomization to week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Secondary variables were HAM-A psychic/somatic clusters, response, and remission, and Clinical Global Impression–Severity of Illness (CGI-S) score.. A total of 409 patients received quetiapine XR (n = 209) or placebo (n = 200). The week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (–10.74; P = .079) vs placebo (–9.61). Secondary variables were generally consistent with the primary analysis, except for a significant reduction in HAM-A total score (week 1) and significant improvements in HAM-A psychic cluster and CGI-S total scores (week 8). Adverse events included dry mouth, somnolence, sedation, headache, and dizziness.. In patients with GAD and an inadequate response to SSRI/ SNRIs, adjunctive quetiapine XR did not show a statistically significant effect for the primary endpoint at week 8, although some secondary endpoints were statistically significant vs placebo. Quetiapine XR was generally well tolerated.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neurotransmitter Uptake Inhibitors; Norepinephrine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

The objective of the study was to evaluate once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in older patients with generalized anxiety disorder (GAD).. An 11-week (9-week treatment; 2-week posttreatment), randomized, double-blind, placebo-controlled study (D1448C00015) of flexibly-dosed quetiapine XR (50-300 mg/day) or placebo conducted at 47 sites (Estonia, Poland, Russia, Ukraine, and USA) between September 2006 and April 2008. Patients (≥66 years) with DSM-IV diagnosis of GAD, Hamilton Anxiety Rating Scale (HAM-A) total score of ≥20 with item 1 (anxious mood) and 2 (tension) scores of ≥2, Clinical Global Impressions-Severity of Illness (CGI-S) score of ≥4, and Montgomery Åsberg Depression Rating Scale (MADRS) total score of ≤16 were eligible for inclusion. Primary endpoint: week 9 change from randomization in HAM-A total score.. Patients were randomized to quetiapine XR (n = 223) or placebo (n = 227). At week 9, quetiapine XR significantly reduced HAM-A total score versus placebo (least squares mean -14.97 versus -7.21; p < 0.001); symptom improvement with quetiapine XR versus placebo was significant at week 1 (p < 0.001). At week 9, quetiapine XR demonstrated significant benefits over placebo for HAM-A response and remission rates, HAM-A psychic and somatic cluster, MADRS total, CGI-S, Pittsburgh Sleep Quality Index global, pain visual analog scale, and Quality of Life, Enjoyment and Satisfaction Questionnaire short form % maximum total scores and Clinical Global Impressions-Improvement (% patients with a score of 1/2) (all p < 0.001). Adverse events (>5% in either treatment group) included somnolence, dry mouth, dizziness, headache, and nausea.. Quetiapine XR (50-300 mg/day) monotherapy is effective in the short term in improving symptoms of anxiety in older patients with GAD, with symptom improvement seen as early as week 1. Tolerability findings were generally consistent with the known profile of quetiapine.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Patient Satisfaction; Quality of Life; Quetiapine Fumarate

The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow-up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM-A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine.

Topics: Acute Disease; Adult; Anti-Anxiety Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Logistic Models; Male; Middle Aged; Placebos; Predictive Value of Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Time Factors; Treatment Outcome; United States; Young Adult

Comorbid anxiety symptoms,in patients with a primary anxiety disorder or a mood disorder, leads to poor patient outcomes and burdens the healthcare system. This pilot study evaluated the feasibility of extended-release quetiapine fumarate (quetiapine XR) for the treatment of patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms compared to a placebo, as an adjunct to antidepressant therapy.. Thirty-nine patients with a diagnosis of a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms were enrolled in this study. Patients with a stable dose of antidepressant therapy were randomized according to a 2:1 probability of receiving either quetiapine XR or a placebo adjunctive treatment for 8 weeks. The efficacy was assessed by the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression of severity (CGI-S) score at baseline, week 1, 4, and 8.. A total of 35 patients were included in this intention-to treat (ITT) population for the efficacy analysis (quetiapine XR: 22 patients; placebo: 13 patients). At week 4, statistically significant differences were observed on both the HAM-A score (p = 0.003) and the CGI-S score (p = 0.025), favouring the quetiapine XR (-13.00 ± 4.14) compared to placebo (-6.63 ± 5.42). However, no statistically significant difference was observed between the two groups with regard to changes from the baseline to week 8 on the HAM-A score (p = 0.332) or the CGI-S score (p = 0.833).. Augmentation of antidepressant treatment with quetiapine XR did not result in clinical improvement according to the outcome measure of anxiety using the HAM-A and CGI-S scores at week 8, among the patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms. However, treatment with quetiapine XR as an adjunct to antidepressant therapy appeared to provide a short-term benefit at 4 weeks. Further study is needed with a larger sample size, randomized controlled design and control of the dosage prescribed.. Clinicaltrials.gov identifier: NCT00912535.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Comorbidity; Delayed-Action Preparations; Dibenzothiazepines; Drug Synergism; Female; Humans; Male; Middle Aged; Mood Disorders; Pilot Projects; Quetiapine Fumarate

The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy for patients with generalized anxiety disorder (GAD). Time-to-event (anxiety symptom recurrence; maximum 52 weeks) multicenter, randomized-withdrawal, parallel-group, double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) following open-label run-in (4-8 weeks) and open-label stabilization (≥ 12 weeks). Primary variable: time from randomization to anxiety event. Secondary variables included: Hamilton Anxiety Rating Scale (HAM-A) total, HAM-A psychic/somatic anxiety factors, Clinical Global Impression-Severity of Illness (CGI-S), and Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores; adverse events (AE) reporting. Four hundred and thirty-two patients, stabilized on quetiapine XR, were randomized to continue quetiapine XR (N=216) or switch to placebo (N=216). Risk of anxiety symptom recurrence was significantly reduced by 81% for quetiapine XR versus placebo: hazard ratio=0.19 (95% confidence interval 0.12-0.31; P<0.001). Fewer patients receiving quetiapine XR (N=22, 10.2%) than placebo (N=84, 38.9%) experienced anxiety symptom recurrence. Significant differences were observed between quetiapine XR and placebo in: HAM-A total, psychic/somatic, CGI-S (all P<0.001) and Q-LES-Q (P<0.05) scores. AEs (>10%) during open-label treatment were dry mouth, sedation, somnolence, dizziness, fatigue, and constipation. During randomized treatment, the most common AEs for quetiapine XR were headache and nasopharyngitis. Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR, with tolerability results consistent with the known profile of quetiapine.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Quetiapine Fumarate; Treatment Outcome

Generalized anxiety disorder (GAD) is a chronic and disabling condition. The aim of this study was to evaluate the effectiveness of low-dose augmentative quetiapine (mean dose=50 mg/day) in patients with GAD and partial/no response to selective serotonin reuptake inhibitors (SSRIs). Twenty patients with GAD and partial/no response to SSRIs were randomized to quetiapine (n=10) or placebo (n=10) for 8 weeks, continuing their treatment with SSRIs. Analyses of variance with repeated measures on Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression (CGIs; severity of illness) were carried out at baseline and after 8 weeks and the number of responders/remitters was computed and compared between the groups. HAM-A scores at baseline were 15.60 (± 4.48) in the placebo group and 18.50 (± 6.59) in the quetiapine group, and at the end-point, HAM-A scores in the placebo group were 10.40 (± 4.88) and 9.20 (± 5.86) in the quetiapine group. A significant time-by-treatment effect was found on the HAM-A (F=5.19, P=0.035) and CGIs scores (F=19.60, P<0.001) in favor of the quetiapine group. The number of responders was numerically superior in the quetiapine group (60 vs. 30%) without reaching statistical significance (χ=1.82, degree of freedom=1, P=0.37, φ=0.30). Remitters were 40% for the quetiapine group versus 20% for the placebo group (χ=0.95, degree of freedom=1, P=0.63, φ=0.22). Low-dose augmentative quetiapine may be an useful treatment option for patients with GAD and partial/no response to SSRIs. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results. Larger randomized controlled trials are warranted to confirm these data.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

To assess the effect of adjunctive treatment with extended-release formulation of quetiapine fumarate (quetiapine XR) to other antidepressants in the treatment of partially responsive, poorly functioning patients with generalized anxiety disorder was assessed.. Twenty four consenting adult outpatients with confirmed DSM-IV diagnosis of generalized disorder were identified. All patients failed at least one 8-week treatment trial with SSRI or SNRI antidepressant. All were treated with quetiapine XR as an add on treatment to citalopram or vanlafaxine antidepressant for at least 12 weeks. The primary efficacy measure was the Clinical Global Impression Scale (CGI-S). Other scales included; the Hamilton Anxiety Scale (HAM-A) scale, Sheehan Disability Scale, and the Abnormal Involuntary Movement Scale (AIMS). Baseline measures prior to adding quetiapine XR were compared to those at 4, 8 and 12 weeks with the adjunctive treatment.. Twenty three patients completed the trial. There was significant rapid resolution of the anxiety symptoms in all effectiveness measures, including the symptoms of anxiety as shown by changes from baseline in HAM-A, and CGI at four weeks. Improvement was maintained to week twelve. Impairments in work, social, and home responsibilities were also reduced significantly, and there were no significant changes in weight at 12 weeks. Patients tolerated the adjunctive treatment well.. Quetiapine XR may have anxiolytic properties and could be used effectively as adjunctive treatment with SSRIs in GAD patients with partial response to SSRs or SNRISs. However double blind randomized trials are needed to support these results.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Young Adult

This study evaluated once-daily, extended-release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 10-week (8-week active treatment/2-week posttreatment drug-discontinuation/tapering phase), double-blind, randomized, placebo-controlled study (D1448C00009). Primary end point was change from randomization at week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Overall, 951 patients with GAD were randomized (quetiapine XR: 50 mg/d, n = 234; 150 mg/d, n = 241; 300 mg/d, n = 241; placebo, n = 235). At week 8, HAM-A total scores significantly (P < 0.001) improved versus placebo (-11.10) with quetiapine XR 50 mg/d (-13.31) and 150 mg/d (-13.54), but not 300 mg/d (-11.87; P = 0.240). At week 1, HAM-A total scores significantly improved versus placebo (-5.94) with quetiapine XR 50 mg/d (-7.47; P < 0.01), 150 mg/d (-8.19; P < 0.001), and 300 mg/d (-7.23; P < 0.01). Versus placebo at week 8, quetiapine XR 50 and 150 mg/d significantly improved HAM-A psychic (P < 0.01 and P < 0.001, respectively) and somatic (P < 0.001; P < 0.01, respectively) cluster scores, HAM-A response (≥ 50% total score reduction; P < 0.05), and Clinical Global Impression-Improvement categorical changes (P < 0.05). For quetiapine XR 150 mg/d, significant (P < 0.05) improvements were seen for HAM-A remission (total score, ≤ 7) and Clinical Global Impression-Severity of Illness scores. For quetiapine XR 300 mg/d, improvements in these secondary variables were not significantly different versus placebo. Pittsburgh Sleep Quality Index global scores improved with all 3 doses (quetiapine: XR 50 mg/d, -4.07 [P < 0.05]; 150 mg/d, -4.38 [P < 0.05]; 300 mg/d, -3.97 [P < 0.05], versus -3.31 with placebo). Adverse events (>10% with quetiapine XR) were dry mouth, somnolence, sedation, dizziness, headache, and fatigue. Quetiapine XR (50/150 mg/d) monotherapy was effective at week 8 in patients with GAD; symptom improvement was seen at week 1 for all doses (50/150/300 mg/d). Safety and tolerability were consistent with the known profile of quetiapine.

Topics: Adolescent; Adult; Aged; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Young Adult

Prospectively planned pooled analysis evaluating efficacy and tolerability of acute quetiapine XR monotherapy in generalised anxiety disorder.. Data from three 10-week, randomised, double-blind, placebo-controlled studies of similar design were analysed.. At Week 8, Hamilton Anxiety Rating Scale (HAM-A) total score significantly improved with quetiapine XR: least squares means change -13.31, p < 0.001 (50 mg/day, n = 452), -14.39, p < 0.001 (150 mg/day, n = 673) and -12.50, p < 0.05 (300 mg/day, n = 444) versus -11.30 placebo; significant (p < 0.001, n = 665) improvements versus placebo were observed with each dose at Week 1. Significant improvements versus placebo at Week 8 are as follows: HAM-A psychic symptom subscale, Montgomery-Åsberg Depression Rating Scale total, Pittsburgh Sleep Quality Index global scores for all quetiapine XR doses; HAM-A response and remission rates, HAM-A somatic symptom subscale score, Clinical Global Impression-Severity of Illness total score, % patients with Clinical Global Impression-Improvement score ≤2 with quetiapine XR 50 and 150 mg/day; and Quality of Life Enjoyment and Satisfaction Questionnaire short form % maximum total score with quetiapine XR 150 mg/day. In the quetiapine XR 50, 150 and 300 mg/day and placebo groups, 13.2%, 16.5%, 24.0% and 5.4% of patients discontinued because of an adverse event, and 1.9%, 1.4%, 3.7% and 1.8% of patients experienced clinically significant changes in glucose. The most common adverse events with quetiapine XR included dry mouth, somnolence, sedation and constipation.. Quetiapine XR monotherapy reduced the symptoms of generalised anxiety disorder, with improvement from Week 1. Adverse events were consistent with the known tolerability profile of quetiapine.

Topics: Adult; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Statistics as Topic; Treatment Outcome

The efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) once-daily monotherapy in generalized anxiety disorder (GAD) was assessed. This multicentre, double-blind, randomized, placebo- and active-controlled, phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk (8-wk active treatment, 2-wk post-treatment drug-discontinuation) study period; 873 patients were randomized to 50 mg or 150 mg quetiapine XR, 20 mg paroxetine, or placebo. Primary endpoint was change from randomization at week 8 in Hamilton Rating Scale for Anxiety (HAMA) total score. At week 8, all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR. Significant separation from placebo (-2.90) in HAMA total score was observed at day 4 for 50 mg quetiapine XR (-4.43, p<0.001) and 150 mg quetiapine XR (-3.86, p<0.05), but not for paroxetine (-2.69). Remission (HAMA total score 7) rates at week 8 were significantly higher for 150 mg quetiapine XR (42.6%, p<0.01) and paroxetine (38.8%, p<0.05) vs. placebo (27.2%). The most common adverse events (AEs) were dry mouth, somnolence, fatigue, dizziness, and headache, for quetiapine XR, and nausea, headache, dizziness for paroxetine. A lower proportion of patients reported sexual dysfunction with quetiapine XR [0.9% (50 mg), 1.8% (150 mg)] than with placebo (2.3%) or paroxetine (7.4%). The incidence of AEs potentially related to extrapyramidal symptoms was: quetiapine XR: 50 mg, 6.8%, 150 mg, 5.0%; placebo, 1.8%; and paroxetine, 8.4%. Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD, with symptom improvement seen as early as day 4.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Young Adult

More data are needed to guide "next step" strategies for patients with generalized anxiety disorder (GAD) remaining symptomatic despite initial pharmacotherapy.. This study prospectively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy.. Adult outpatients with GAD were recruited from 2004 to 2007 at two academic centers. Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day. Those remaining symptomatic (Hamilton Anxiety Scale [HAM-A] >or= 7) at week 10 were randomized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day.. For participants receiving paroxetine CR (n = 50), there was a significant reduction in HAM-A scores (baseline mean +/- SD = 22.4 +/- 4.2 to endpoint mean +/- SD = 11.2 +/- 6.9; paired t = 12.1, df = 49, t < 0.0001) with 40% (n = 20) achieving remission. Counter to our hypothesis, we did not find significant benefit for quetiapine augmentation of continued paroxetine CR (HAM-A reduction mean +/- SD = 2.6 +/- 5.8 points quetiapine, 0.3 +/- 5.5 points placebo; t = 0.98, df = 20, p = n.s.) in the randomized sample (n = 22) with relatively minimal additional improvement overall in phase 2.. Although conclusions are considered preliminary based on the relatively small sample size, our data do not support the addition of quetiapine to continued paroxetine CR for individuals with GAD who remain symptomatic after 10 weeks of prospective antidepressant pharmacotherapy and suggest that further research examining strategies for GAD refractory to antidepressants is needed.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Paroxetine; Personality Inventory; Prospective Studies; Quetiapine Fumarate

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

Social anxiety disorder (SAD) is one of the most common anxiety disorders. Reports have suggested an effect of the atypical antipsychotic quetiapine in anxiety disorders. Given these considerations, we conducted a controlled trial of quetiapine monotherapy in SAD. Fifteen patients were randomized to quetiapine (up to 400 mg/day) or placebo for 8 weeks. The Brief Social Phobia Scale (BSPS) and the Clinical Global Impression of Improvement Scale (CGI-I) were the primary outcome measures, while the Social Phobia Inventory (SPIN) and the Sheehan Disability Inventory (SDI) were secondary measures. There was no significant difference on the BSPS score at endpoint between the quetiapine and placebo groups. There was a significant time effect but not a significant time x treatment group interaction, indicating that both the quetiapine and placebo patients did better over the course of the trial. 20% of the quetiapine patients had a 50% or greater drop in BSPS score at the end of the trial compared to baseline, while 0% had such a drop in the placebo group. There was no significant difference in responders (CGI-I score of 1 or 2) versus non-responder (CGI-I score of 3 or more) across the groups. However, 40% of quetiapine patients and 0% of the placebo patients showed much or very much improvement on the CGI-I. The Number Needed to Treat (NNT) to be a responder on the CGI-I was 3. Significant time effects were noted for the SPIN and SDI, as well as a significant time x treatment effect in favor of quetiapine on the SPIN. Additionally, quetiapine showed a large effect size on the SPIN.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Data Interpretation, Statistical; Dibenzothiazepines; Double-Blind Method; Endpoint Determination; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Social Behavior Disorders

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

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Treatment Outcome; United States

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

This analysis of data from the open-label extension (OLE) phases of three randomized clinical trials of quetiapine in patients with schizophrenia (n=415) was undertaken to investigate whether the initial improvements in anxiety and depressive symptoms were maintained during long-term treatment. The mean (95% confidence interval [CI]) change from the acute phase baseline in the Factor I score of the Brief Psychiatric Rating Scale (BPRS), which includes somatic concern, anxiety, guilt feelings, and depression, was calculated at the OLE baseline and at various time points up to 156 weeks. After 6 weeks of treatment with quetiapine during the acute phase, the mean (95% CI) change in the BPRS Factor I score was -1.13 (-1.23, -1.04) and after 156 weeks, it was -1.33 (-1.78, -0.87). Therefore, the efficacy of quetiapine for the treatment of anxiety and depressive symptoms is maintained in long-term treatment.

Topics: Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Brief Psychiatric Rating Scale; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Long-Term Care; Male; Middle Aged; Patient Compliance; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

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

Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus. Maternally deprived rats had a depressive-like behavior in the forced swimming test and an increase in the HDAC and DNMT activities in the hippocampus and NAc. Treatment with quetiapine reversed depressive-like behavior and reduced the DNMT activity in the hippocampus. This is the first study to show the antidepressant-like effect of quetiapine in animals subjected to MD and a protective effect by quetiapine in reducing epigenetic changes induced by stress in early life. These results reinforce an important role of quetiapine as therapy for MDD.

Topics: Analysis of Variance; Animals; Antidepressive Agents; Anxiety Disorders; Brain; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Exploratory Behavior; Female; Histone Acetyltransferases; Histone Deacetylases; Immobility Response, Tonic; Male; Maternal Deprivation; Pregnancy; Quetiapine Fumarate; Rats; Rats, Wistar; Swimming

The objective of this study was to evaluate trends in prescribing of the second-generation antipsychotic medication quetiapine to adults in the province of Alberta from 2008 to 2013 through examination of dispensed prescriptions, and diagnoses associated with users of quetiapine in 2013.. We analysed administrative data from Alberta Health; the Alberta Pharmaceutical Information Network (PIN) Dispenses health data set, the Practitioner Payments (Fee-For-Service claims) health data set and the Population Registry health data set. These data sets allowed us to identify discrete quetiapine recipients for each calendar year from 2008 to 2013. To evaluate diagnoses associated with users of quetiapine, we evaluated diagnostic codes used by physicians in billings claims in 2013.. Quetiapine use increased over the 6-year time period studied. In 2008, there were 16,087 unique quetiapine recipients in Alberta (7.2 per 1000). By 2013, there were 35,314 unique quetiapine recipients (13.3 per 1000). Use by women was higher than men at all time points. Depression was most common diagnosis associated with quetiapine recipients, which was present in 56% of users of quetiapine. Other common diagnoses associated with quetiapine use included neurotic disorders, bipolar disorder and sleep disturbances.. The current study of quetiapine use in the province of Alberta provides confirmatory data of the increasing use of quetiapine for the treatment of depression and anxiety disorders. Safe and rational prescribing practices must be encouraged in light of the modest advantages of quetiapine over no treatment as an adjunctive treatment of major depression, and the known harms of this medication.

Topics: Adult; Alberta; Antipsychotic Agents; Anxiety Disorders; Depressive Disorder; Drug Prescriptions; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Sex Distribution; Young Adult

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

In 2004, the American Diabetes Association (ADA) released treatment guidelines recommending metabolic screening for children and adolescents before and after initiation of second-generation antipsychotics. Prior studies showed that the guidelines coincided with a small increase in glucose testing of children and adults but had limited follow-up. This study sought to evaluate changes in metabolic screening of children initiating second-generation antipsychotics around the time of the 2004 guidelines and in the following eight years.. Study patients (N=52,407) were identified in a large nationwide commercial insurance claims database for the period January 1, 2003, through December 31, 2011. The study population was a cohort of nondiabetic new users of second-generation antipsychotics who were ages 5-18. Glucose and HbA1c tests completed before and after second-generation antipsychotic initiation were identified with Current Procedural Terminology-4 codes. Metabolic screening was also examined by second-generation antipsychotic agent prescribed and psychiatric diagnosis.. The proportion of patients receiving a glucose test preinitiation increased from 17.9% in 2003 to 18.9% in 2004, and testing postinitiation increased from 14.7% to 16.6% in the same period. The slight increase in glucose testing was not sustained; the proportion tested dropped in the following years before rising again in 2008. Glucose screening was most common for patients taking aripiprazole. Patients with a diagnosis of hyperkinetic disorder were less likely to be tested. HbA1c testing was less frequent but had a similar usage pattern.. The small improvement in metabolic screening immediately after the 2004 ADA guidelines were issued was not sustained. Overall, metabolic screening rates remained suboptimal throughout the study period.

Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Blood Glucose; Child; Child, Preschool; Cohort Studies; Conduct Disorder; Databases, Factual; Depressive Disorder; Diabetes Mellitus; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hyperkinesis; Male; Mass Screening; Mental Disorders; Olanzapine; Piperazines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Thiazoles

To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine.. This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis.. After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively.. Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

Topics: Adolescent; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Blood Pressure; Body Mass Index; British Columbia; Child; Child Development Disorders, Pervasive; Child, Preschool; Cholesterol; Cholesterol, HDL; Cohort Studies; Dyslipidemias; Female; Humans; Incidence; Longitudinal Studies; Male; Mental Disorders; Metabolic Syndrome; Mood Disorders; Obesity; Overweight; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Waist Circumference

A 27-year-old man treated with quetiapine for anxiety disorder developed hypertriglyceridaemia-induced acute pancreatitis and diabetic ketoacidosis. He was otherwise physically healthy with no family history of hyperlipidaemia. Despite aggressive intensive therapy he died of multiorgan failure within 36 h from initial presentation. While second-generation antipsychotics are well known to be causally linked to diabetes and hyperlipidaemia, this is to my knowledge the first-described case of a fatal triad of extreme hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine. Clinicians should be aware of this rare clinical presentation since rapid progression to multiorgan failure can occur. Early supportive therapy should be initiated. Lactescent serum and ketoacidosis in severe acute pancreatitis should not be overlooked-initiate insulin therapy and possibly plasmapheresis in case of extreme hypertriglyceridaemia.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Delayed Diagnosis; Diabetic Ketoacidosis; Diagnosis, Differential; Dibenzothiazepines; Dose-Response Relationship, Drug; Fatal Outcome; Humans; Hypertriglyceridemia; Male; Pancreas; Pancreatitis, Acute Necrotizing; Phobic Disorders; Psychotic Disorders; Quetiapine Fumarate; Tomography, X-Ray Computed

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

Topics: Adult; Anti-Anxiety Agents; Antimanic Agents; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Clonazepam; Delayed-Action Preparations; Delusions; Dibenzothiazepines; Drug Monitoring; Drug Therapy, Combination; Humans; Male; Mianserin; Mirtazapine; Neutropenia; Polypharmacy; Quetiapine Fumarate; Suicidal Ideation; Treatment Outcome; Valproic Acid

Topics: Affective Symptoms; Antipsychotic Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Humans; Mood Disorders; Quetiapine Fumarate; Schizophrenia

The purpose of this study was to determine preventive and protective effects of chronic orally administration with quetiapine (QUE) against anxiety-like behavior and cognitive impairments in rats exposed to the enhanced single prolonged stress (ESPS), an animal model that is used to study post-traumatic stress disorder (PTSD), and to detect changes in the expression of cortical phosphorylated p44/42 extracellular-regulated protein kinase (pERK1/2). Before or after exposure to ESPS paradigm, consisting of 2-h constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, rats were given orally QUE (10 mg/kg daily) for 14 days. Animals were then tested in the open field (OF), elevated plus-maze (EPM), and Morris water maze (MWM). Brains were removed for immunohistochemical staining of pERK1/2. ESPS exposure resulted in pronounced anxiety-like behavior compared to unexposed animals. ESPS-exposed animals also displayed marked learning and spatial memory impairments. However, QUE treatment (both before and after ESPS exposure) significantly ameliorated anxiety-like behavior, learning and spatial memory impairments. ESPS also markedly reduced the expression of pERK1/2 in the prefrontal cortex, medial amygdala nucleus, and cingulate gyrus. Both before and after ESPS exposure QUE treatments significantly elevated the reduced pERK1/2 expression in the three brain regions. QUE has preventive and protective effects against stress-associated symptoms and the changes in pERK1/2 functions may be associated with the pathophysiology of traumatic stress and the therapeutic efficacy of anti-PTSD therapy.

Topics: Anesthetics, Inhalation; Animals; Antipsychotic Agents; Anxiety Disorders; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Electroshock; Ether; Extracellular Signal-Regulated MAP Kinases; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neurons; Prefrontal Cortex; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Stress Disorders, Post-Traumatic; Swimming; Unconsciousness

There is growing evidence to show that atypical antipsychotic quetiapine might exert an anxiolytic effect in patients. Nevertheless, the mechanism underlying this effect has not yet been fully explored. Like other anxiolytic drugs, quetiapine exhibits partial agonistic activity toward serotonergic 1A (5HT1A) receptors. The involvement of the serotonin system in anxiety, particularly of 5HT1A receptors, has been widely documented. In this study we have investigated whether different doses of quetiapine (5, 10, and 30 mg/kg, oral gavage) administered to C57BL6/N mice could produce an anxiolytic effect in the Vogel conflict test, a classical model of anxiety, and whether or not the selective 5HT1A antagonist WAY100635 (0.1 mg/kg, subcutaneously) might prevent such an effect. Our results show that 10 mg/kg quetiapine exhibits an anxiolytic effect, that is, at least in part, 5HT1A-mediated, because it is completely eliminated by WAY100635.

Topics: Animals; Anti-Anxiety Agents; Antipsychotic Agents; Anxiety; Anxiety Disorders; Behavioral Research; Conflict, Psychological; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Mice; Mice, Inbred C57BL; Models, Animal; Quetiapine Fumarate; Rats; Rats, Wistar; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists

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

The aim of the current study was to evaluate quetiapine doses used across diagnosis categories in a sample of psychiatric inpatients.. Discharge letters of all adult inpatients who had received quetiapine between 1999 and 2005 were retrospectively reviewed. Logistic regressions were carried-out to assess links between quetiapine discharge dosage (> or =800 mg/day vs. <800 mg/day), diagnostic categories, substance abuse or dependence, benzodiazepine discharge doses, age and sex.. The data of 231 patients were included. Five hundred and for discharge documents were analyzed: 113 for psychotic disorders, 190 for personality disorders, 134 for bipolar and schizoaffective bipolar disorders, 29 for unipolar depression or anxiety disorders, and 35 for mental retardation. Considering psychotic disorders as a reference group, patients with personality disorders were statistically significantly less likely to be in the high quetiapine dosage group at discharge (P = 0.007, OR = 0.1 and CI [0.03; 0.6]).. Quetiapine seems to be used in a variety of clinical situations, with a wide range of doses and a lower dosage in patients treated for personality disorders.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Cross-Sectional Studies; Depressive Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Patient Discharge; Patient Readmission; Personality Disorders; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies

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

Generalized anxiety disorder (GAD) is a chronic illness that leads to substantial impairments in quality of life. This post-hoc analysis used combined data from three 8-week quetiapine extended-release trials to investigate the reliability, validity, and responsiveness of the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q (SF)] in 2588 patients with GAD. The baseline Q-LES-Q (SF) score showed a Cronbach's alpha value of 0.86, indicative of reliability. Validity analyses for Q-LES-Q (SF) identified significant correlations with clinical efficacy measures (r>0.34 at week 8; P<0.001) and significant discrimination between patient groups categorized by symptom severity (P<0.001). Responsiveness was shown by significant differences in mean changes in Q-LES-Q (SF) scores at week 8 between patients defined according to the Hamilton Rating Scale for Anxiety response or remission criteria (P<0.001). The minimum clinically important Q-LES-Q (SF) score change was identified to be 6.80 points. Using this definition, response rates were significantly greater with quetiapine extended-release 150 mg versus placebo in individual trials and the combined population (P < or = 0.02). This analysis shows the overall reliability, validity, and responsiveness of the Q-LES-Q (SF) as a measure of overall quality of life and satisfaction in patients with GAD.

Topics: Adolescent; Adult; Aged; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quality of Life; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Reproducibility of Results; Surveys and Questionnaires

Several studies have reported the findings of fluorine-18-labeled fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) in benign lung disease with diffuse pulmonary injury; however, the characteristics and effectiveness of FDG-PET imaging for interstitial pneumonitis have not been substantiated. We report two cases of drug-induced pneumonitis in two patients treated for breast cancer who were diagnosed by FDG-PET examination. Both the cases showed diffuse interstitial infiltration in the bilateral lungs on computed tomography, but the degree of FDG accumulation was different. It is probable that the degree of FDG accumulation reflected the activity of the drug-induced pneumonitis. The present cases show very interesting FDG-PET imaging findings of diffuse lung disease.

Topics: Aged; Anxiety Disorders; Brain Neoplasms; Breast Neoplasms; Dibenzothiazepines; Female; Fluorodeoxyglucose F18; Humans; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Pneumonia; Positron-Emission Tomography; Quetiapine Fumarate; Sensitivity and Specificity; Tomography, X-Ray Computed; Whole Body Imaging

Topics: Alcoholism; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bromazepam; Depression; Dibenzothiazepines; Hospitalization; Humans; Life Change Events; Male; Middle Aged; Quetiapine Fumarate; Self Administration; Substance-Related Disorders

Generalized anxiety disorder (GAD) is a chronic disorder associated with significant morbidity and disability. Traditional therapies are associated with poor levels of remission, and often result in troublesome side effects.. This was a 12-week, open-label, flexible-dose study to assess the efficacy and tolerability of quetiapine as an adjunctive treatment to traditional medication. 40 outpatients with GAD who had not achieved remission following at least 8 weeks of an adequate dose of traditional therapy were enrolled. The primary endpoint was the mean change from pre-treatment to week 12 in the Hamilton Anxiety Rating Scale (HAM-A) total scores. Secondary endpoints included: the proportion of patients achieving remission (HAM-A total score of < or =10 at week 12), Clinical Global Impressions-Severity of Illness (CGI-S), Clinical Global Impressions-Global Improvement (CGI-I), Pittsburgh Sleep Quality Index (PSQI) and Penn State Worry Questionnaire (PSWQ).. Adjunctive quetiapine (mean dose 386mg/day at week 12) significantly reduced the HAM-A total scores from pre-treatment (29.8+/-9.0) to week 12 (9.0+/-10.2) (-20.6; p<0.001). The HAM-A remission rate was 72.1% at week 12. Adjunctive quetiapine resulted in a significant reduction in all efficacy measures by study end. Quetiapine was well tolerated: the most common adverse event (AE) was sedation, with no incidence of serious AEs and no clinically significant changes in vital signs, weight (mean gain 0.5kg at week 12) or laboratory assessments.. The results of this small pilot trial suggest that quetiapine adjunctive to traditional therapy may be a useful treatment in patients with GAD or treatment-resistant GAD, and warrant further investigation.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Anxiety Disorders; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Personality Inventory; Pilot Projects; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Dibenzothiazepines; Humans; Male; Prisoners; Quetiapine Fumarate; Substance-Related Disorders; Treatment Refusal

Stimulants have been the mainstay of treatment for children with Attention-deficit/hyperactivity Disorder (ADHD). However, stimulants have been controversially purported to precipitate and exacerbate tics. Atomoxetine, a selective norepinephrine inhibitor, was introduced as a safe non-stimulant alternative treatment for ADHD children with comorbid tics or TS. We are presenting two children with ADHD, in which atomoxetine, at relatively low doses, exacerbated and precipitated tics. The diagnoses of ADHD and tic disorder were based on clinical observations and standardized rating scales. Case 1, an 8-year-old boy, had history of stimulant-induced tics. This child was placed on atomoxetine reported to be safe for patients with tics. This patient's tic control was adequate prior to atomoxetine treatment. However, while on atomoxetine, the patient promptly experienced tic exacerbation. Case 2, a 6-year-old boy, had no previous history of stimulant therapy and was receiving citalopram due to a comorbid anxiety disorder. Atomoxetine was initiated for the treatment of ADHD with improvement in the ADHD symptoms. But, upon a mild dose increase, the patient presented tic precipitation consisting primarily of neck twitches. Both cases experienced a decrease in tic activity when atomoxetine was discontinued, but tics did not fully resolve, causing psychosocial disturbance. Atypical neuroleptics were used with good results. Periodic assessments of the need for continued neuroleptic treatment were emphasized. These two children exemplify atomoxetine's potential to exacerbate and precipitate tics in children with ADHD. Independent controlled studies are needed to determine if atomoxetine should be used in children with ADHD and comorbid tic disorders or TS.

Topics: Adrenergic Uptake Inhibitors; Antipsychotic Agents; Anxiety Disorders; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Citalopram; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Propylamines; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Tics

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

In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Canada; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lamotrigine; Lithium Carbonate; Mood Disorders; Olanzapine; Quetiapine Fumarate; Triazines; Valproic Acid

Quetiapine is a novel antipsychotic, which is efficacious in the treatment of positive and negative symptoms in schizophrenia. Research has shown that atypical antipsychotic also reduce the craving and consumption for stimulants and alcohol. Due to Quetiapine's particulars and the promising receptor profile concerning addiction medicine, we set out to examine the tolerability and efficacy concerning relapse prevention of withdrawn alcoholics suffering from craving and affective symptoms.. Our case observations attempted to evaluate nine alcoholics after withdrawal suffering from persisting craving, sleep disorder, excitement, depressive symptoms or anxiety symptoms. The patients were treated with quetiapine as relapse prevention and we followed them up in our outpatient clinic.. Eight out of nine patients were abstinent under quetiapine over a period of 2-7 months. One of these patients relapsed after he stopped taking the preparation at his own initiative after 10 weeks. The ninth patient stopped taking the preparation immediately because of swollen nasal mucosae. All target symptoms disappeared in the patients after an average of (mean+/-S.D.) 24.5+/-18.1 days. The overall tolerability was considered to be very good; however, initial sleepiness appeared in four patients.. Although uncontrolled case observations can only be interpreted with caution quetiapine seems to deserve further investigation and may hold the potential for preventing alcohol relapse in alcoholics suffering from additional above-mentioned symptoms.

Topics: Adult; Affect; Affective Symptoms; Alcoholism; Antipsychotic Agents; Anxiety Disorders; Depressive Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychomotor Agitation; Quetiapine Fumarate; Secondary Prevention; Sleep Stages; Sleep Wake Disorders; Temperance; Time Factors; Treatment Outcome

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 have demonstrated that the atypical antipsychotic drugs prevent cell death in PC12 cells induced by various cytotoxins and have protective effects on methamphetamine-induced neurotoxcity in rats. The present study was designed to examine the possible effects of chronic administration of quetiapine, an atypical antipsychotic drug, on the anxiety-like behavioural consequences of a neurotoxic regimen of dl-amphetamine. Rats were treated with quetiapine (10 mg/kg/day; i.p.) for 33 days. During days 15-19 of this period, the animals were given dl-amphetamine (20 mg/kg/day; s.c.) 1 h after the administration of quetiapine. The repeated administration of dl-amphetamine resulted in a decrease of tyrosine hydroxylase (TH) immunostaining in the caudate putamen, hyperthermia, and anxiety-like behavioural changes. The behavioural changes were indicated by a significant increase in the time spent in the light box in the light/dark box test, an increase in the ratios of ambulation distance inside the inner circle over the total ambulation distance and rearings inside the inner circle over the total rearings in the open field test, and an increase in the time spent in open arms in the elevated plus-maze test. Chronic administration of quetiapine significantly attenuated the dl-amphetamine-induced hyperthermia, and the anxiety-like behavioural changes in the light/dark box and in the open field tests. These results suggest that quetiapine can normalize the dl-amphetamine-induced anxiety-like behavioural changes, and might be helpful in the treatment for amphetamine-induced emotional changes.

Topics: Amphetamine; Analysis of Variance; Animals; Antipsychotic Agents; Anxiety Disorders; Behavior, Animal; Body Temperature; Brain; Cell Count; Dibenzothiazepines; Drug Administration Schedule; Drug Interactions; Exploratory Behavior; Immunohistochemistry; Male; Maze Learning; Neurotoxins; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Reaction Time; Time Factors; Tyrosine 3-Monooxygenase

Some antipsychotic medications prescribed for the treatment of psychoses, mood disorders or post-traumatic stress disorder in patients with coexisting substance dependence disorders (SDD) have reduced substance dependence. We studied the potential benefits of quetiapine in the treatment of SDD.. We conducted a retrospective chart review of data for 9 patients who were admitted to a 28-day residential rehabilitation program designed for individuals with SDD during a 3-month period from January 2003 through March 2003 and treated with quetiapine for nonpsychotic anxiety. These patients also met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for alcohol, cocaine and/or methamphetamine dependence and substance-induced anxiety disorder. The patients were assessed using the Hamilton-D Rating Scale for Depression (Ham-D), a 10-point Likert scale to measure alcohol or drug cravings, and random Breathalyzer and urine drug screens.. Quetiapine was generally well tolerated. Only 1 of the 9 patients stopped taking the medication because of increased anxiety. Other patients reported improvement in sleep and anxiety. The mean decrease in Ham-D score at discharge for the responders was 18.5 (p < 0.005). The biggest decreases on the Ham-D occurred on the subscales of insomnia, agitation, somatic anxiety, psychologic anxiety, hypochondriasis and obsessional symptoms. The mean decrease in the Likert 10-point craving scale was 5.9 for the responders (p < 0.005). These patients' periodic Breathalyzer and urine test results suggested that they remained abstinent from alcohol and other drug use.. Quetiapine was beneficial in the treatment of SDD in patients with nonpsychotic anxiety.

Topics: Adult; Alcoholism; Amphetamine-Related Disorders; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Cocaine-Related Disorders; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Methamphetamine; Middle Aged; Nebraska; Patient Admission; Quetiapine Fumarate; Retrospective Studies; Substance Abuse Detection; Substance Abuse Treatment Centers; Treatment Outcome

Two children with Tourette's syndrome and comorbid disorders were treated with quetiapine, an atypical antipsychotic successfully used in patients with psychoses and schizophrenia with low incidence of extrapyramidal side effects. Clinical observations and standardized rating scales suggested that this drug produced beneficial effects on tics and other symptoms. Adverse effects (at low doses) were minimal. Because it was suggested that tic efficacy of the newer antipsychotics was related to higher D2 occupancy (with the exception of quetiapine and clozapine, which have relatively low D2 activity), it is hypothesized that tic patients are D2 sensitive and need lower doses of medications. These children were treated naturalistically and were reported retrospectively because of their encouraging outcomes. However, these findings should be interpreted with caution, because no contrast groups, drug withdrawal, or placebo were utilized. Controlled studies are needed to determine the efficacy of quetiapine in the treatment of Tourette's syndrome.

Topics: Adolescent; Antipsychotic Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Basal Ganglia Diseases; Depressive Disorder; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Tourette Syndrome

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Comorbidity; Depressive Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone