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PubMed2000

A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy.

BACKGROUND: Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile. METHODS: Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. After 3 weeks of treatment, D2 and 5-HT2a occupancy were measured using positron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were included to examine the effects of the drug 2 to 3 hours after last dose. RESULTS: Quetiapine was an effective antipsychotic and improved the extrapyramidal symptoms and prolactin level elevation noted at baseline. It achieved these results with minimal (0%-27%) D2 occupancy 12 hours after the last dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours. CONCLUSIONS: Quetiapine shows a transiently high D2 occupancy, which decreases to very low levels by the end of the dosing interval. Quetiapine's low D2 occupancy can explain its freedom from extrapyramidal symptoms and prolactin level elevation. The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect. Future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.

Adult↗
PubMed2000

Treatment of depressive mood in schizophrenia with the atypical antipsychotic quetiapine.

Two patients with schizophrenia and depressive mood experienced remission in both their psychotic and depressive symptoms during treatment with the atypical antipsychotic quetiapine. These case reports illustrate the antipsychotic clinical efficacy of quetiapine and its antidepressant effects in the treatment of patients with schizophrenia and depressive mood.

Adult↗
PubMed2004

Quetiapine for schizophrenia.

BACKGROUND: Quetiapine is an atypical antipsychotic with, theoretically, a low propensity for movement disorder adverse effects. It is used for the treatment of schizophrenia and other psychoses. OBJECTIVES: To determine the effects of quetiapine for schizophrenia in comparison to placebo, and other antipsychotics. SEARCH STRATEGY: Electronic searches of the Cochrane Schizophrenia Group's Register of Trials (February 2003), Biological Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1),EMBASE (1980-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. We contacted AstraZeneca Pharmaceuticals for information regarding unpublished trials. The review was updated in February 2003. SELECTION CRITERIA: All randomised controlled trials where adults with schizophrenia or similar illnesses were assigned to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. We analysed data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI). Only homogeneous data were interpreted as favouring treatment or control. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics (NNH). We calculated relative risk (RR) for dichotomous data, and weighted mean differences (WMD) for continuous data. MAIN RESULTS: Despite the fact that 3443 people were randomised in 12 quetiapine studies, there are almost no data on service utilisation, economic outcomes, social functioning and quality of life. Over half of those within the quetiapine versus placebo comparison were lost to follow up (53% quetiapine vs 61% placebo, n=716, 4RCTs, RR 0.84 CI 0.7 to 0.9, NNT 11 CI 7 to 55) so it is impossible to interpret any ratings of global or mental state within this comparison with confidence. People allocated quetiapine, however, did not have more movement disorders than those given placebo (n=395, 2 RCTs, RR needing medication for EPSE 0.62 CI 0.3 to 1.2). The same applies to the comparison of >/= 250 mg/day quetiapine with < 250 mg/day quetiapine (49% dropout >/= 250 mg/day vs 58% < 250 mg/day, n=1066, 3 RCTs, RR 0.84 CI 0.8 to 0.9, NNT 11 CI 7 to 29). It should be noted that two deaths occurred in the higher dose group (n=618, 1 RCT, RR 0.1 CI 0.0 to 2.1). When quetiapine was compared with typical antipsychotics, about 36% of both groups failed to complete the short-term studies (n=1624, 6 RCTs, RR 0.87 CI 0.8 to 1.0). Average change in global state was heterogeneous and equivocal (n=762, 3 RCTs, WMD in short term 0.19 CI 0.00 to 0.38, I squared 76%). Mental state measures were also equivocal (n=1247, RR not improved 0.97 CI 0.9 to 1.1) including specific measures of negative symptoms (n=305, 1 RCT, MD change in SANS short term 0.94 CI -0.2 to 2.0). Movement disorders were less prevalent for those allocated quetiapine (n=1117, 4 RCTs, RR needing medication for extrapyramidal adverse effects 0.47 CI 0.4 to 0.6, NNT 4 CI 4 to 5, I squared 88%). Dry mouth (n=649, 2 RCTs, RR short term 2.85 CI 1.5 to 5.6, NNH 17 CI 7 to 65) and sleepiness (n=959, 3 RCTs, RR 1.51 CI 1.1 to 2.2, NNH 18 CI 8 to 181) may also be more prevalent for people given quetiapine compared with the older drugs. In the quetiapine versus risperidone comparison, over 30% of people left the study before completion (n=728, 1 RCT, RR 0.94 CI 0.7 to 1.2). Four people, all treated with quetiapine, died during the study (n=728, 1 RCT, RR 2.86 CI 0.2 to 52.8). Continuous mental state measures did not show clear differences between the two drugs (n=637, 1 RCT, MD PANSS 1.2 CI -2.0 to 4.4). However, considerably fewer people given quetiapine needed medication for extrapyramidal side effects compared with those allocated to risperidone (n=712, 1 RCT, RR 0.27 CI 0.2 to 0.5, NNT 11 CI 10 to 16). Quetiapine caused more dizziness (n=728, 1 RCT, RR 1.85 CI 1.0 to 3.3, NNH 18 CI 7 to 487), more dry mouth (n=728, 1 RCT, RR 2.11 CI 1.2 to 3.8, NNH 14 CI 6 to 82) and more sleepiness than risperidone (n=728, 1 RCT, RR 2.03 CI 1.4 to 2.9, NNH 7 CI 4 to 17). REVIEWERS' CONCLUSIONS: Quetiapine is effective for the treatment of schizophrenia, but it is not much different from first-generation antipsychotics and risperidone with respect to treatment withdrawal and efficacy. In comparison to first-generation antipsychotics and risperidone, quetiapine has a lower risk of movement disorders but higher risks of dizziness, dry mouth and sleepiness. More clearly reported pragmatic randomised controlled trials should be carried out to determine its position in everyday clinical practice. Studies of medium and long-term effects, including cost-effectiveness, quality of life, social functioning and service utilisation, in comparison with the effects of typical and atypical antipsychotics should be priority areas.

Adult↗
PubMed2006

The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease.

BACKGROUND: Aggression, agitation or psychosis occur in the majority of people with dementia at some point in the illness. There have been a number of trials of atypical antipsychotics to treat these symptoms over the last five years, and a systematic review is needed to evaluate the evidence in a balanced way. OBJECTIVES: To determine whether evidence supports the use of atypical antipsychotics for the treatment of aggression, agitation and psychosis in people with Alzheimer's disease. SEARCH STRATEGY: The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 December 2004 using the terms olanzapine, quetiapine, risperidone, clozapine, amisulpride, sertindole, zotepine, aripiprazole, ziprasidone. This Register contains articles from all major healthcare databases and many ongoing trials databases and is updated regularly. SELECTION CRITERIA: Randomised, placebo-controlled trials, with concealed allocation, where dementia and psychosis and/or aggression were assessed. DATA COLLECTION AND ANALYSIS: 1. Two reviewers extracted data from included trials2. Data were pooled where possible, and analysed using appropriate statistical methods3. Analysis included patients treated with an atypical antipsychotic, compared with placebo MAIN RESULTS: Sixteen placebo controlled trials have been completed with atypical antipsychotics although only nine had sufficient data to contribute to a meta-analysis and only five have been published in full in peer reviewed journals. No trials of amisulpiride, sertindole or zotepine were identified which met the criteria for inclusion. The included trials led to the following results:1. There was a significant improvement in aggression with risperidone and olanzapine treatment compared to placebo.2. There was a significant improvement in psychosis amongst risperidone treated patients.3. Risperidone and olanzpaine treated patients had a significantly higher incidence of serious adverse cerebrovascular events (including stroke), extra-pyramidal side effects and other important adverse outcomes.4. There was a significant increase in drop-outs in risperidone (2 mg) and olanzapine (5-10 mg) treated patients.5. The data were insufficient to examine impact upon cognitive function. AUTHORS' CONCLUSIONS: Evidence suggests that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extra-pyramidal symptoms. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is marked risk or severe distress. Although insufficient data were available from the considered trials, a meta-analysis of seventeen placebo controlled trials of atypical neuroleptics for the treatment of behavioural symptoms in people with dementia conducted by the Food and Drug Administration (using data not in the public domain) suggested a significant increase in mortality (OR 1.7).

Aggression↗
PubMed2006

Haloperidol alone or in combination for acute mania.

BACKGROUND: The main objectives in treating mania are to control dangerous behaviour, reduce suicide, produce appropriate acute sedation and shorten the episode of mood disturbance. Among different drugs, haloperidol has for many years been used in treating psychotic patients, but it has a troublesome side effect profile. OBJECTIVES: To assess the effects of haloperidol for the treatment of mania in comparison with placebo or other active drugs, either as monotherapy or add-on treatment. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (11 October 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1966-2003), EMBASE (1980-2003), CINAHL (1982-2003), PsycINFO (1872-2003) and reference lists. We also contacted experts, triallists and pharmaceutical companies in the field. SELECTION CRITERIA: Randomised trials comparing haloperidol with placebo or other active treatment in the treatment of acute manic or mixed episodes in patients with bipolar disorder or schizoaffective disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS: Fifteen trials involving 2022 people were included. Compared to placebo, haloperidol was more effective at reducing manic symptoms, both as monotherapy (Weighted Mean Difference (WMD) -5.85, 95% Confidence Interval (CI) -7.69 to -4.00) and as adjunctive treatment to lithium or valproate (WMD -5.20, 95% CI -9.26 to -1.14). There was a statistically significant difference, with haloperidol being less effective than aripiprazole (Relative Risk (RR) 1.45, 95% CI 1.22 to 1.73). No significant differences between haloperidol and risperidone, olanzapine, carbamazepine or valproate were found. Compared with placebo, a statistically significant difference in favour of haloperidol in failure to complete treatment (RR 0.74, 95% Cl 0.57 to 0.96) was reported. Haloperidol was associated with less weight gain than olanzapine (RR: 0.28, 95% CI 0.12 to 0.67), but with a higher incidence of tremor (RR: 3.01, 95% CI 1.55 to 5.84) and other movement disorders. AUTHORS' CONCLUSIONS: There is some evidence that haloperidol is an effective treatment for acute mania. From the limited data available, there was no difference in overall efficacy of treatment between haloperidol and olanzapine or risperidone. Some evidence suggests that haloperidol could be less effective than aripiprazole. Referring to tolerability, when considering the poor evidence comparing drugs, clinicians and patients should consider different side effect profiles as an important issue to inform their choice.

Amisulpride↗
PubMed1999

Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease.

Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.

Aged↗
PubMed2004

Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia.

Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.

Adult↗
PubMed2006

Increased deep sleep in a medication-free, detoxified female offender with schizophrenia, alcoholism and a history of attempted homicide: effect of concomitant administration of quetiapine and citalopram.

BACKGROUND: An increased amount of deep sleep has been shown to be associated with antisocial personality disorder. This phenomenon has also been observed in a habitually violent female offender with schizophrenia and alcohol dependence. AIM: To evaluate sleep patterns in this patient and compare them with those of healthy, pro-social women of similar age, and in the same patient over time after treatment. METHOD: Multiple measures of sleep were taken over two consecutive nights with the presenting patient and with three age-matched healthy women. One year after the patient was established on atypical antipsychotic (quetiapine), and antidepressant (SSRI) medication (citalopram) her sleep evaluation was repeated. In each case only the second night's recordings were used in analyses. RESULTS: The patient differed significantly from the three healthy women on most sleep measures. After a year on the medication, the patient's sleep had improved and the non-REM sleep measures had come into the normal range. She had also shown a sustained clinical and behavioural improvement. DISCUSSION AND IMPLICATIONS: The literature suggests that both drugs had a part to play in the improvements in sleep, symptomatology and behaviour. The possibility that improvement in deep sleep is secondary to citalopram and that it is this that was specifically associated with violence reduction seems worthy of further study.

Adult↗
PubMed2004

Preliminary experience with adjunctive quetiapine in patients receiving selective serotonin reuptake inhibitors.

Treatment of depression and anxiety disorders with selective serotonin reuptake inhibitors (SSRIs) has been shown by numerous studies to be generally effective. Less well understood is how clinically to address the residual anxiety symptoms a significant minority of such patients treated with SSRIs continue to experience. We assessed quetiapine as adjunctive therapy to SSRIs for patients with anxiety symptoms complicating a depressive or anxiety disorder. Patients receiving a stable dosage of an SSRI for at least 6 weeks who also had persistent anxiety symptoms (Hamilton Anxiety scale [HAM-A] > or =16), were enrolled in a 9-week, open-label, variable dose study. Changes in clinical status were assessed with the Hamilton Depression Rating Scale (HAM-D), HAM-A, and State Anxiety Inventory (SAI). Statistically and clinically significant reductions of > or =50% in the HAM-D and HAM-A occurred by the second week of treatment in 10 of the 11 patients. These improvements continued throughout the study along with a significant improvement on the SAI scale. The most frequent side effects reported were mild dry mouth, constipation, and transient drowsiness with dose escalation. The results provide evidence that quetiapine may be an effective adjunctive treatment for recalcitrant anxiety symptoms in individuals treated with SSRIs for either anxiety or depressive disorders. Given the open-label design of the trial, more rigorous studies are clearly indicated.

Dibenzothiazepines↗
PubMed2004

Quetiapine is effective against anxiety and depressive symptoms in long-term treatment of patients with schizophrenia.

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.

Adult↗
PubMed2007

Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study.

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.

Adult↗
PubMed2007

Quetiapine in anorexia nervosa patients: an open label outpatient pilot study.

OBJECTIVES: The main objective of the study was to determine whether quetiapine was effective in reducing scores on the positive and negative syndrome scale (PANSS) in anorexia nervosa (AN) patients. Secondary objectives included determining whether quetiapine was effective in reducing symptoms of anxiety and depression. In addition, the effect on weight was determined. METHOD: In an open label design, 19 patients with AN but without schizophrenia or schizoaffective disorder were given 150-300 mg quetiapine daily over a 10 week period. Results were analyzed using last observation carried forward (LOCF). RESULTS: Fourteen patients completed the study and all but one of the 5 patients who dropped out returned for an early termination visit. Scores on the total, general psychopathology, and depression scales of the PANSS declined significantly (p = .024, .010, .0005, respectively) at LOCF. There were improvements in several measures of anxiety, depression, and obsessive compulsive symptoms. Mean weight gain was modest at 1.6 lbs (0.73 kg). Adverse events were generally mild and no patients discontinued due to adverse events CONCLUSION: Quetiapine was well-tolerated and patients had significant improvements in several subscales of the PANSS as well as decreases in measures of anxiety and depression.

Adolescent↗