Quetiapine Treatment Research Articles

Association between implicit motor learning and neurological soft signs in schizophrenia

IntroductionSchizophrenia (SZ) patients present subtle motor deficits known as Neurological Soft Signs (NSS). Those deficits encompass impairments of motor coordination, sequencing of complex motor acts and sensory integration. It has been shown that SZ patients present also deficits of higher motor functions as implicit motor learning. Growing number of studies indicate that both NSS and implicit motor learning deficits are associated with impairments of common cortico-cerebellar pathways, however relationship between these two deficits has not been evaluated yet.ObjectivesTo assess NSS and implicit motor learning in SZ patients.AimsTo evaluate associations between NSS and implicit motor learning scores in SZ patients.MethodsTwenty schizophrenia patients and 20 healthy controls were examined. Patients were under olanzapine, clozapine or quetiapine treatment. NSS were assessed with Neurological Evaluation Scale (NES). Implicit motor learning were assessed with a use of Serial Reaction Time Task.ResultsSZ patients presented statistically higher NSS scores than healthy controls (P < 0.001) and presented no signs of implicit motor learning. There was statistically significant negative correlation between implicit motor learning score and total score of neurological soft signs (r = −0.44), sequence of motor acts subscore (r = −0.54) and sensory integration subscore (r = −0.47) in SZ patients group (P < 0.05).ConclusionsThere is association between implicit motor learning deficits and neurological soft signs in SZ patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effects of short-term quetiapine treatment on emotional processing, sleep and circadian rhythms

Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers. Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep-wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks. Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times. These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action.

Heavy Alcohol Drinking Associated Akathisia and Management with Quetiapine XR in Alcohol Dependent Patients.

Heavy drinking contributes to involuntary body movements such as akathisia. Quetiapine has been shown to alleviate symptoms of akathisia; however, its efficacy in the alcohol dependent population is not well established. Thus, we aimed to identify efficacy of Quetiapine in treating akathisia in very heavy drinking alcohol dependent patients. 108 male and female heavy alcohol consuming study participants received 13 weeks of Quetiapine XR. Drinking history (Timeline Followback, TLFB), depression (Montgomery-Asberg Depression Rating Scale, MADRS), and movement (Barnes Akathisia Scale, BARS) measures were collected at baseline (0 W), week 6 (6 W), and week 12 (12 W). The role of drinking, symptoms of depression, and efficacy of Quetiapine for treating akathisia were assessed. In patients with no symptoms of depression (low MADRS), Quetiapine treatment decreased symptoms of akathisia. Patients with clinically significant depression (high MADRS) reported a significant increase in akathisia measures at 6 W which eventually decreased at 12 W to below baseline levels. The increase in akathisia at 6 W corresponded with a significant increase in the patients' total drinks and heavy drinking pattern. Treatment with Quetiapine progressively lowered the occurrence of akathisia in alcohol dependent patients who do not show symptoms of depression. Quetiapine treatment lowered akathisia over time in heavy drinkers who had clinically significant symptoms of depression.

Pulmonary hypertension due to lithium therapy: a case report

Lithium is accepted as the gold standard for long term treatment in bipolar affective disorder. However, this specific drug has various side effects, which restrict its use such as cardiologic. To our knowledge, there is only one reported case of pulmonary hypertension due to lithium therapy in the literature. Here we are presenting a case that developed pulmonary hypertension associated with long-term lithium treatment without any prior diagnosis of a cardiac or pulmonary disease. A 43-year-old female patient had a diagnosis of bipolar disorder. Before lithium treatment, her cardiac examination and laboratory tests were normal. After a five year regular lithium 1200 mg/day lithium and 300-600 mg/day quetiapine treatment she had palpitation. It was investigated in detail; a cardiologist diagnosed her as pulmonary hypertension. Other known causes of pulmonary hypertension were investigated and eliminated both clinically and laboratory. In these conditions pulmonary hypertension was attributed to lithium treatment and we decided to change her pharmacotherapy. During exchange, she had a manic episode. Forty-five days after lithium discontinuation, PAP was detected 30-35 mmHg in the cardiac examination. Although this patient had concurrent quetiapine medication when the pulmonary pressure decreased, lithium was discontinued but quetiapine was continued in higher doses. Current researches about lithium focus on the behavioural and neurochemical effects of this drug. Although some authors think that a new side effect should be expected for drugs like lithium, which was in use over half a century, we have to be aware of the side effects. However, any possible new side effect of lithium has to be analyzed in detail, and, before to attribute the responsibility of a new side effect to lithium, compelling evidence is required.

Antidepressant Efficacy of the Antipsychotic Quetiapine:Pharmacokinetics, Pharmacodynamics and Clinical Data

Quetiapine (QTP) is an is an atypical antipsychotic, that was approved in 1997 by American Food and Drug Administration (FDA) for schizophrenia, both in adults and adolescents (13-17 years). Since 2003 this drug was approved also for the treatment of maniac episode in bipolar adults and adolescents (10-17 years) then in 2006 FDA extended the use of QTP to bipolar depression episodes and in 2008 to the maintenance treatment of bipolar disorder. In 2009 QTP starts to be used also as add on therapy of major depressive disorder combined to antidepressants, without FDA consent. Actually this drug, in "off label" use, is employed also for monotherapy of unipolar depression. QTP treatment was generally well tolerated. The incidence of treatment-emergent mania/hypomania was lower with QTP compared with the antidepressant paroxetine and placebo.

Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in bipolar depression (CEQUEL): a 2 × 2 factorial randomised trial

Depressive symptoms are a major cause of disability in bipolar disorder and there are few safe and effective treatments. The combination of lamotrigine plus quetiapine potentially offers improved outcomes for people with bipolar depression. We aimed to determine if combination therapy with quetiapine plus lamotrigine leads to greater improvement in depressive symptoms over 12 weeks than quetiapine monotherapy plus lamotrigine placebo. In this double-blind, randomised, placebo-controlled, parallel group, 2 × 2 factorial trial (CEQUEL), patients with DSM-IV bipolar disorder I or II, who were aged 16 years or older, and required new treatment for a depressive episode, were enrolled from 27 sites in the UK. Patients were randomly assigned (1:1) by an adaptive minimisation algorithm to lamotrigine or placebo and to folic acid or placebo. Participants and investigators were masked to the treatment groups. The primary outcome was improvement in depressive symptoms at 12 weeks with the Quick Inventory of Depressive Symptomatology-self report version 16 (QIDS-SR16). Analysis was by modified intention-to-treat. This trial is registered with EUdraCT, number 2007-004513-33. Between Oct 21, 2008, and April 27, 2012, 202 participants were randomly assigned; 101 to lamotrigine and 101 to placebo. The mean difference in QIDS-SR16 total score between the group receiving lamotrigine versus the placebo group at 12 weeks was -1·73 ([95% CI -3·57 to 0·11]; p=0·066) and at 52 weeks was -2·69 ([-4·89 to -0·49]; p=0·017). Folic acid was not superior to placebo. There was a significant interaction (p=0·028), with folic acid reducing the effectiveness of lamotrigine at 12 weeks. The mean difference on QIDS-SR16 was -4·14 ([95% CI -6·90 to -1·37]; p=0·004) for patients receiving lamotrigine without folic acid compared with 0·12 ([-2·58 to 2·82]; p=0·931) for those receiving lamotrigine and folic acid. Addition of lamotrigine to quetiapine treatment improved outcomes. Folic acid seems to nullify the effect of lamotrigine. CEQUEL should encourage clinicians and patients to consider lamotrigine for bipolar depression, but also to be aware that concurrent folic acid might reduce its effectiveness. Medical Research Council.

Evaluation of the Reinforcing Effect of Quetiapine, Alone and in Combination with Cocaine, in Rhesus Monkeys.

There are several case reports of nonmedicinal quetiapine abuse, yet there are very limited preclinical studies investigating quetiapine self-administration. The goal of this study was to investigate the reinforcing effects of quetiapine alone and in combination with intravenous cocaine in monkeys. In experiment 1, cocaine-experienced female monkeys (N = 4) responded under a fixed-ratio (FR) 30 schedule of food reinforcement (1.0-g banana-flavored pellets), and when responding was stable, quetiapine (0.003-0.1 mg/kg per injection) or saline was substituted for a minimum of five sessions; there was a return to food-maintained responding between doses. Next, monkeys were treated with quetiapine (25 mg, by mouth, twice a day) for approximately 30 days, and then the quetiapine self-administration dose-response curve was redetermined. In experiment 2, male monkeys (N = 6) self-administered cocaine under a concurrent FR schedule with food reinforcement (three food pellets) as the alternative to cocaine (0.003-0.3 mg/kg per injection) presentation. Once choice responding was stable, the effects of adding quetiapine (0.03 or 0.1 mg/kg per injection) to the cocaine solution were examined. In experiment 1, quetiapine did not function as a reinforcer, and chronic quetiapine treatment did not alter these effects. In experiment 2, cocaine choice increased in a dose-dependent fashion. The addition of quetiapine to cocaine resulted in increases in low-dose cocaine choice and number of cocaine injections in four monkeys, while not affecting high-dose cocaine preference. Thus, although quetiapine alone does not have abuse potential, there was evidence of enhancement of the reinforcing potency of cocaine. These results suggest that the use of quetiapine in cocaine-addicted patients should be monitored.

A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study

BackgroundCognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. MethodsThe design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. ResultsThere was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. ConclusionAlthough the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Effects of repeated quetiapine treatment on conditioned avoidance responding in rats

The present study characterized the behavioral mechanisms of avoidance–disruptive effect of quetiapine in the conditioned avoidance response test under two behavioral testing (2 warning signals vs. 1 warning signal) and two drug administration conditions (subcutaneous vs. intravenous). In Experiments 1 and 2, well-trained adult male Sprague-Dawley rats were tested under the subcutaneous (s.c.) quetiapine treatment (5.0, 15.0, 25.0, 50.0mg/kg) for 7 days in a novel procedure consisting of two conditioned stimuli (CS) (white noise serving as CS1 and pure tone as CS2). Only the highest dose (50.0mg/kg) produced a persistent suppression of the avoidance response without impairing the escape response. The magnitude of suppression of the CS1 avoidance was similar to that of CS2 avoidance. No significant group difference was found in the quetiapine (15.0mg/kg, s.c.) challenge test, indicating a lack of a long-term quetiapine effect. In Experiment 3, well-trained rats were tested under the intravenous (i.v.) quetiapine treatment (3.0, 9.0, 15.0mg/kg) for 5 days and challenged with quetiapine (6.0mg/kg, i.v. followed by 9.0mg/kg, s.c.). Only the white noise was used as the CS. Similar to what was being observed in Experiments 1 and 2, intravenously administered quetiapine dose-dependently suppressed avoidance responding during the drug test days, but did not alter drug sensitivity in the challenge days. Thus, quetiapine does not appear to show a preferential inhibition of the avoidance response to a less salient stimulus; and prior quetiapine treatment (s.c. and i.v.) does not cause a sensitization or tolerance to quetiapine.

Disruptions of sensorimotor gating, cytokines, glycemia, monoamines, and genes in both sexes of rats reared in social isolation can be ameliorated by oral chronic quetiapine administration

The pathogenesis of schizophrenia in patients with metabolic abnormalities remains unclear. Our previous study demonstrated that isolation rearing (IR) induced longitudinal concomitant changes of pro-inflammatory cytokine (pro-CK) levels and metabolic abnormalities with a developmental origin. However, the general consensus, believes that these abnormalities are caused by antipsychotic treatment in schizophrenic patients. The IR paradigm presents with face, construct, and predictive validity for schizophrenia. Therefore, we employed IR rats of both sexes to examine whether chronic quetiapine (QTP, a second-generation antipsychotic medication) treatment induces disruptions of metabolism (body weight, blood pressure, and the glycemic and lipid profiles) or cytokines [interleukin (IL)-1 beta, IL-6, IL-10, interferon-gamma, and tumor necrosis factor (TNF)-alpha], and further, whether it reverses deficits of behaviors [locomotor activity and prepulse inhibition (PPI)] and the expression of monoamines (dopamine and serotonin) and related genes (Htr1a, Htr2a, Htr3a, Drd1a, and Gabbr2). IR induced higher levels of pro-CK, dysglycemia, blood pressure, locomotor activity, and impaired PPI, simultaneously destabilizing cortico-striatal monoamines and relevant genes in both sexes, while QTP demonstrated dose-dependent reversal of these changes, suggesting that QTP might reduce the pro-CKs to regulate these abnormalities. Our data implied that antipsychotics may not be the solitary factor causing metabolic problems in schizophrenia and suggested that inflammatory changes may play a vital role in the developmental pathophysiology of schizophrenia and related metabolic abnormalities.

Abstract 4189: Analgesic effect of quetiapine on the cancer induced bone pain animal model

Abstract Background: Cancer induced bone pain is one of the most common pain in patients with advanced cancer. Because of treatment associated side effects, it has been reported that more than half of cancer patients have inadequate and undermanaged pain control. Therefore, new mechanism-based therapies need to be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug that has superior therapeutic effects in patients with schizophrenia and other neurological disorders like depression. We reported that a study of anti-inflammatory effect of quetiapine on collagen induced arthritis mouse model. Now we focused on the potential analgesic effects of quetiapine on the cancer induced bone pain (CIBP) animal model and the mechanism of bone pain evaluated by various nociceptors expression. Methods: Fifteen male C3H/HeN mice were randomly divided into five groups: Control, CIBP, CIBP + quetiapine treatment, CIBP + opioid treatment and CIBP + melatonin treatment. Treatments were started when mouse showed positive signs of bone tumor until the day 28, according to the protocol, daily for 12 days. Pain thresholds of CIBP mouse model were measured by aesthesiometer for each group. At the end of the treatment period, tissue of mouse tibia were removed and quantitative and qualitative evaluation of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 expression were done. Results: The data showed that mouse behavior about pain thresholds was marked improved in CIBP + quetiapine treatment group compared with CIBP group. The expression of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 in CIBP + quetiapine treatment group was significantly lower than those in CIBP groups. Conclusions: These results suggest analgesic effect of quetiapine on CIBP animal model and provide the possibility that TRPV and ASICs could be a potential target of cancer pain management. Citation Format: Keon Uk Park, Mi Hwa Heo, Jin Young Kim, Ilseon Hwang, Hun Mo Ryoo. Analgesic effect of quetiapine on the cancer induced bone pain animal model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4189. doi:10.1158/1538-7445.AM2015-4189

Impact of Quetiapine Treatment on Duration of Hypoactive Delirium in Critically Ill Adults: A Retrospective Analysis

Because delirium remains a common consequence of critical illness, and reducing its duration has been shown to have a positive impact on patient outcomes during and after an intensive care unit (ICU) stay, we sought to determine whether treatment of hypoactive delirium with quetiapine reduces the duration of delirium compared with no pharmacologic treatment. Retrospective cohort study. Three medical-surgical ICUs within the two main campuses of an academic tertiary care hospital system. A total of 113 adults with documented hypoactive delirium during an ICU length of stay (LOS) of at least 72hours between August 2013 and September 2014; 52 patients received at least one dose of quetiapine during their hypoactive delirium course, and 61 patients received no pharmacologic delirium treatment. Patients were screened for hypoactive delirium using the Confusion Assessment Method-ICU (CAM-ICU) and the Richmond Agitation Sedation Scale (RASS). The primary outcome was time to first resolution of delirium, and secondary outcomes included ICU and hospital LOS, and duration of mechanical ventilation. To assess potential adverse effects of quetiapine, the number of RASS assessments deeper than goal and the total number of RASS assessments documented during the delirium course were recorded for all patients. Daily progress notes and discharge documentation were surveyed to assess for new onset of extrapyramidal symptoms or torsade de pointes. Median duration of hypoactive delirium was shorter in the quetiapine-treated group compared with the no-quetiapine group (1.5 vs 2.0days, p=0.04), and time to extubation after screening positive for delirium trended favorably toward quetiapine-treated patients (3 vs 5days, p=0.08). There were no significant differences in ICU or hospital LOS, and safety outcomes were similar between groups. In this mixed ICU population, treatment of hypoactive delirium with quetiapine was safe and reduced the duration of delirium compared with standard care alone. Prospective placebo-controlled studies are needed to further assess the role of antipsychotics in hypoactive delirium.

Quetiapine attenuates cognitive impairment and decreases seizure susceptibility possibly through promoting myelin development in a rat model of malformations of cortical development

Developmental delay, cognitive impairment, and refractory epilepsy are the most frequent consequences found in patients suffering from malformations of cortical development (MCD). However, therapeutic options for these psychiatric and neurological comorbidities are currently limited. The development of white matter undergoes dramatic changes during postnatal brain maturation, thus myelination deficits resulting from MCD contribute to its comorbid diseases. Consequently, drugs specifically targeting white matter are a promising therapeutic option for the treatment of MCD. We have used an in utero irradiation rat model of MCD to investigate the effects of postnatal quetiapine treatment on brain myelination as well as neuropsychological and cognitive performances and seizure susceptibility. Fatally irradiated rats were treated with quetiapine (10mg/kg, i.p.) or saline once daily from postnatal day 0 (P0) to P30. We found that postnatal administration of quetiapine attenuated object recognition memory impairment and improved long-term spatial memory in the irradiated rats. Quetiapine treatment also reduced the susceptibility and severity of pentylenetetrazol-induced seizures. Importantly, quetiapine treatment resulted in an inhibition of irradiation-induced myelin breakdown in the cerebral cortex and corpus callosum. These findings suggest that quetiapine may have beneficial, postnatal effects in the irradiated rats, strongly suggesting that improving MCD-derived white matter pathology is a possible underlying mechanism. Collectively, these results indicate that brain myelination represents an encouraging pharmacological target to improve the prognosis of patients with MCD.

Impact of genetic variability in CYP2D6, CYP3A5, and ABCB1 on serum concentrations of quetiapine and N-desalkylquetiapine in psychiatric patients.

To investigate the impact of genetic variability in CYP2D6, CYP3A5, and ABCB1 on steady-state serum concentrations of quetiapine and the active metabolite, N-desalkylquetiapine, in psychiatric patients. Measured serum concentrations of quetiapine and N-desalkylquetiapine from patients with biobanked DNA samples were included retrospectively from a routine therapeutic drug monitoring database. The impact of CYP2D6, CYP3A5, and ABCB1 (345C>T) genotypes on dose-adjusted serum concentrations (C/D ratios) of quetiapine and N-desalkylquetiapine was investigated by multivariate mixed model analysis. In total, 289 patients with 633 serum measurements were included. In the multivariate analysis, mean C/D ratio of N-desalkylquetiapine was estimated to be 33% and 22% higher in inherent CYP2D6 poor metabolizers (P = 0.03) and heterozygous extensive metabolizers (P < 0.001), respectively, compared with inherent extensive metabolizers. The ABCB1 3435C>T polymorphism and CYP3A5 genotype had no significant influence on either of the substances in the present material. Genetic variability in CYP2D6 contributes to the interindividual variability in steady-state serum concentrations of N-desalkylquetiapine. Although the metabolite exhibits relevant pharmacological activity, the quantitative effect of CYP2D6 genotype on serum concentration of N-desalkylquetiapine is probably of limited clinical relevance for quetiapine treatment.

Neurological and Cerebellar Soft Signs in Schizophrenia and Bipolar Disorder

Introduction Neurological soft signs (NSS) refer to the subtle dysfunctions of motor coordination, sequencing of complex motor acts and sensory integration. NSS are linked with schizophrenia and bipolar disorder, contributing to common biological background of those diseases. Growing number of studies present that both disorders share various functional and structural cerebellar dysfunctions, however schizophrenia and bipolar disorder have not been compared yet in terms of cerebellar motor dysfunctions. Objectives To assess neurological and cerebellar soft signs in schizophrenia and bipolar disorder Aim To evaluate whether both disorders share similar rate of neurological and cerebellar soft signs Methods 29 patients with schizophrenia, 30 bipolar disorder patients and 24 healthy controls were examined. Patients were under olanzapine, clozapine or quetiapine treatment. In case of BD patients mood stabilizer has been permitted. NSS were assessed with Neurological Evaluation Scale (NES). Cerebellar soft signs were evaluated by International Co-operative Ataxia Rating Scale (ICARS). Results Schizophrenia and bipolar disorder patients did not differ significantly in NES and ICARS total scores nor in any of their subscales. Both schizophrenia and bipolar disorder patients presented statistically higher total NES and ICARS scores than healthy controls (p Conclusions Both schizophrenia and bipolar disorder patients reveal similar motor dysfunctions in terms of neurological and cerebellar soft signs.

Effects of Quetiapine on Platelets in Major Depression

1.1 Objectives: Test the prevailing hypothesis that depressive illness is associated with platelet hyperactivity and that treatment with an atypical antipsychotic with established antidepressant efficacy – quetiapine - will normalize platelet activity. 1.2 Methods: Forty-seven outpatients with major depressive disorder (MDD) and 27 healthy controls (HC) without evidence of cardiovascular disease were enrolled. Behavioral rating scales and medical tests preceded baseline assessments of (1) platelet-rich plasma (PRP) aggregometry and (2) whole blood flow cytometry (P-selectin surface labeling). The measures were repeated in those MDD subjects who completed 8 weeks (n=27) or 12 weeks (n=19) of treatment with quetiapine. 1.3 Results: Untreated MDD compared to HC subjects displayed more platelet aggregation when PRP was stirred agonist-free (p=0.021). Other platelet measurements at baseline such as in vitro agonist-stimulated PRP aggregometry or P-selectin expression by flow cytometry did not distinguish MDD from HC subjects. After 8 weeks on quetiapine, a reduced (now normal) agonist-free aggregatory response to stirring (p=0.035) was observed. By 12 weeks the aggregometry response to arachidonic acid (AA) was also lowered (p=0.016 vs. pretreatment; p=0.001 vs. HC). Other agonist additions (ADP, epinephrine, or collagen) failed to distinguish MDD from HC. There were no significant associations between mood rating scores and any form of platelet activity at any time point on quetiapine. 1.4 Limitations: High percentage of dropouts attributable to dose-related side effects limited the post-treatment assessments. 1.5 Conclusions: The hypothesis that untreated depression is associated with more active platelets, was confirmed, but this finding was confined to the “resting”, or agonist-free state. Quetiapine treatment normalized this resting activity and led to a lower-than-normal response to AA-induced aggregation after 12 weeks of treatment. These findings confirm that 8 weeks treatment with quetiapine can normalize at least one form of platelet hyperactivity, but the lower-than-healthy response to AA after 12 weeks on quetiapine warrants further study.

Neurofunctional effects of quetiapine in patients with bipolar mania

Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood. Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans. At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p < 0.001), and increased activation in the right orbitofrontal cortex (OFC) (p = 0.002); there was a significant association between increased right OFC activity and YMRS improvement (p = 0.003). These findings are consistent with suggestions that mania involves a loss of emotional modulatory activity in the prefrontal cortex--restoration of the relatively greater elevation in prefrontal activity widely observed in euthymic patients is associated with clinical improvement. It is not clear, however, whether changes are related to quetiapine treatment or represent a non-specific marker of affective change.

Neuroleptic Malignant Syndrome Associated with Quetiapine Treatment in a Patient with Ventriculoperitoneal Shunt

Introduction: Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening idiosyncratic reaction during the use of antipsychotic drugs, usually beginning in the first 2 weeks of the treatment. NMS is generally manifested by muscle rigidity, hyperthermia, autonomic instability, altered mental status, tremors, elevated serum creatinine phosphokinase, and leukocytosis. Case Report: A 26-year-old male patient who had a ventriculoperitoneal (V-P) shunt was admitted to the emergency department with complaints of loss of consciousness, fever, respiratory distress, and palpitations. In his history, we learned that treatment of quetiapine 25 mg/day was initiated 6 months ago. After physical examination and laboratory results, the patient, who had a V-P shunt, was primarily considered shunt dysfunction or infection. But, with laboratory parameters and radiographic examinations, we moved away from this diagnosis. He was evaluated as NMS due to the history of antipsychotic drug using, fever, rigidity, tachycardia, tachypnea, confusion, and increase of creatine phosphokinase for the preliminary diagnosis. Since there was no any etiological factor that could explain the clinical process, he was admitted to the medical intensive care with a diagnosis of NMS.Conclusion: NMS is a disorder that can be life-threatening and must be recognized by clinicians

Effects of quetiapine treatment on cocaine self-administration and behavioral indices of sleep in adult rhesus monkeys.

Clinical literature suggests a link between substance abuse and sleep disturbances. Quetiapine, an atypical antipsychotic, has shown efficacy in treating sleep disturbances, with clinical studies showing promise for quetiapine as a treatment for cocaine abuse. The goal of this study was to examine the effects of quetiapine on cocaine self-administration and behavioral indices of sleep in monkeys. Seven adult male rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a choice paradigm of food (1.0-g pellets) and cocaine (0.003-0.3 mg/kg per injection) presentation. First, monkeys received acute pretreatment (45 min) with quetiapine (25-75 mg, p.o.) prior to choice sessions; three cocaine doses were studied in combination with quetiapine. Next, the effect of chronic (14-16 days) quetiapine treatment (25-250 mg, p.o., BID) was examined in combination with the lowest preferred cocaine dose (≥80 % cocaine choice). Behavioral indices of sleep, based on activity measures obtained during lights-out, were recorded throughout the study. Acute quetiapine decreased cocaine choice in four of the seven monkeys. Chronic quetiapine treatment resulted in initial decreases in cocaine choice, but tolerance developed to these effects. Acute doses of quetiapine did not improve sleep efficiency the following night nor did chronic quetiapine. The first night after discontinuing quetiapine treatment resulted in significant decreases in sleep efficiency and increases in nighttime activity. These findings do not offer support for the use of quetiapine as a monotherapy for treatment of cocaine abuse nor as an adjunct therapy to treat sleep disturbances associated with stimulant abuse.

Open-label pilot study of quetiapine treatment for cannabis dependence

Background: There are no efficacious pharmacotherapies for cannabis dependence. The effects of quetiapine are well matched to the symptoms of cannabis withdrawal and could be useful in the treatment of cannabis dependence. Objectives: To evaluate quetiapine for the treatment of cannabis dependence and determine the optimal dosing. Methods: In an eight-week open-label outpatient pilot trial, we evaluated the feasibility of quetiapine treatment for cannabis dependence in 15 outpatients. Quetiapine was gradually titrated to 600 mg or the maximum tolerated dose. Results: The mean study retention was 6.5 weeks (±2.3), with 67% of participants completing all eight weeks of the trial. The mean maximum dose achieved was 197 mg/day (range: 25–600 mg/day). Only two of the 15 participants were able to achieve the target dose of 600 mg daily. There were no serious adverse events and no participants were discontinued from the trial due to adverse effects. The most common reported adverse effects were fatigue (80% of participants) and somnolence (47%). From baseline to week 8, the modeled overall decrease in daily dollar value of marijuana was 76.3% (CI: 63.4%, 84.7%). Over the eight weeks of the study, there was a 46.9% (CI: 11%, 68.3%) decrease in urine tetrahydrocannabinol-9-carboxylic acid (THCOOH) levels. Conclusions: These preliminary results are promising in that quetiapine treatment was tolerated by cannabis-dependent patients and associated with decreased cannabis use. The recommended maximum target dose for cannabis-dependent patients is 300 mg daily. These preliminary data support further evaluation of quetiapine as a treatment for cannabis dependence.