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Central serous chorioretinopathy (CSCR) is a chorioretinal disease that is characterized by central vision loss and is usually seen in middle-aged males. It has been associated with the use of various drugs, including corticosteroids and phosphodiesterase inhibitors. We present the case of a 36-year-old male who developed CSCR after a few weeks of irregular use of quetiapine for his sleep problems. The clinical findings of the patient improved shortly after he stopped using the drug, and at the end of the two-month period complete recovery was observed. Quetiapine is an atypical antipsychotic that exerts its effects on dopamine and serotonin receptors. There are studies showing that these neurotransmitters may play a role in the control of choroidal vascular permeability, which is the underlying cause of CSCR. Therefore, we believe that quetiapine may have a causal relationship with CSCR. To our knowledge, this is the first case report documenting full recovery from quetiapine associated CSCR.

Objective Poisonings contribute significantly to morbidity and mortality of patients. Some patients have numerous contacts to a poison information center, indicating repeated poisoning exposures. Information on the involved substances is necessary to explore methods to prevent self-harm and reduce mortality. The objective of this study was to characterize the patient population with repeated poison exposures in Denmark and identify the substances involved. Methods This study was a retrospective cohort study of enquiries to the nationwide Danish Poison Information Centre and the Danish National Patient Registry. The databases were used to identify patients with more than five individual poisoning episodes within a 12-month-period between 1 January 2013, and 31 December 2017. Results One hundred and thirty-seven patients and 995 patients met the inclusion criteria in the Danish Poison Information Centre and the Danish National Patient Registry, respectively. The majority were women (82.5% and 66.3% for the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively). The mean age was 24.7 and 29.5 years. Psychiatric comorbidities were frequent with 74.5% and 67.0% suffering from personality disorders and 70.1% and 54.5% from affective disorders in the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively. One thousand seven hundred and fifty-two poisoning episodes were identified in the Danish Poison Information Centre database, and the most common types of substance were ‘pharmaceuticals’ (1,420 episodes). The most common medications ingested were quetiapine, paracetamol and cyclizine. Median number of contacts to the Danish Poison Information Centre was 10. Patients with one or more poisoning episodes involving cyclizine had on average 11.4 poisoning episodes involving cyclizine. In the Danish National Patient Registry cohort 80.9% were alive after 10 years co, Objective: Poisonings contribute significantly to morbidity and mortality of patients. Some patients have numerous contacts to a poison information center, indicating repeated poisoning exposures. Information on the involved substances is necessary to explore methods to prevent self-harm and reduce mortality. The objective of this study was to characterize the patient population with repeated poison exposures in Denmark and identify the substances involved. Methods: This study was a retrospective cohort study of enquiries to the nationwide Danish Poison Information Centre and the Danish National Patient Registry. The databases were used to identify patients with more than five individual poisoning episodes within a 12-month-period between 1 January 2013, and 31 December 2017. Results: One hundred and thirty-seven patients and 995 patients met the inclusion criteria in the Danish Poison Information Centre and the Danish National Patient Registry, respectively. The majority were women (82.5% and 66.3% for the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively). The mean age was 24.7 and 29.5 years. Psychiatric comorbidities were frequent with 74.5% and 67.0% suffering from personality disorders and 70.1% and 54.5% from affective disorders in the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively. One thousand seven hundred and fifty-two poisoning episodes were identified in the Danish Poison Information Centre database, and the most common types of substance were ‘pharmaceuticals’ (1,420 episodes). The most common medications ingested were quetiapine, paracetamol and cyclizine. Median number of contacts to the Danish Poison Information Centre was 10. Patients with one or more poisoning episodes involving cyclizine had on average 11.4 poisoning episodes involving cyclizine. In the Danish National Patient Registry cohort 80.9% were alive after 10 years compared to 97.7% in the b

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

Case presentation: An 85-year-old woman with a history of depression treated with polypharmacy including selective serotonin reuptake inhibitor presented to the emergency department with head, and upper and lower limb tremors four hours after increasing the dose of quetiapine from 12.5 milligrams (mg) per day to 25 mg/day. She was diagnosed with serotonin syndrome (SS), and all medications except clotiazepam were discontinued. The symptoms subsided within 48 hours.Discussion: The use of atypical antipsychotics alone seldom increases the risk of SS. However, combining atypical antipsychotics with serotonergic agents increases the risk of SS because the activity of serotonin receptor subtype 1A is relatively enhanced. This report suggests that physicians should be aware that even a small increase in quetiapine could pose a risk of developing SS.

Case presentation: An 85-year-old woman with a history of depression treated with polypharmacy including selective serotonin reuptake inhibitor presented to the emergency department with head, and upper and lower limb tremors four hours after increasing the dose of quetiapine from 12.5 milligrams (mg) per day to 25 mg/day. She was diagnosed with serotonin syndrome (SS), and all medications except clotiazepam were discontinued. The symptoms subsided within 48 hours.Discussion: The use of atypical antipsychotics alone seldom increases the risk of SS. However, combining atypical antipsychotics with serotonergic agents increases the risk of SS because the activity of serotonin receptor subtype 1A is relatively enhanced. This report suggests that physicians should be aware that even a small increase in quetiapine could pose a risk of developing SS.

Antipsychotics (APs), especially second-generation antipsychotics, are being increasingly used around the world. At the same time their off-label use has also increased worldwide, as well as in Finland. The aim of our study was to find out the off-label prescribing of APs in Finland among physicians in different healthcare units. The study was conducted as a questionnaire survey. Particular attention was paid to practices between psychiatrists and other physicians (mostly general practitioners and occupational health doctors). Similar studies have not been conducted on this topic in Finland before. Altogether 216 physicians answered the questionnaire. The most common indications for off-label prescription were insomnia and anxiety, and this was evident for both psychiatrists as well as other physicians. Quetiapine was the one most commonly prescribed off-label AP. Over one-third of psychiatrists (39%) and about one-third of other physicians (30%) did not give instructions on the length of the treatment. The metabolic values were reported to be followed by 44% of the psychiatrists and by 18% of other physicians. Nearly two-thirds of all respondents thought that off-label use had more benefits than harms. Compared to other physicians, psychiatrists prescribed APs for off-label use more frequently and for more varied psychiatric conditions. Off-label use of APs seems to be a clinical reality in Finland. There is need for further studies on efficacy and adverse effects of APs in off-label use, and also a need for clinical guidelines on monitoring the patients using APs off-label.

Objectives: Brexpiprazole is a new dopamine partial agonist antipsychotic in the same class as aripiprazole. This paper will briefly review brexpiprazole and compare it with aripiprazole. Conclusion(s): Brexpiprazole and aripiprazole are both partial agonists at dopamine D2, and serotonin 5-HT1A and antagonists at serotonin 5-HT2A and noradrenergic alpha1B receptors. However, the two drugs are significantly different in potencies at various receptors; neurochemical profiles predict that brexpiprazole may be comparable with aripiprazole in its antipsychotic efficacy but may cause less akathisia, extrapyramidal side effects (EPS) and activation. In pivotal trials brexpiprazole demonstrated antipsychotic efficacy in short and long-term studies; it was also found to be an effective adjunct in patients with major depression resistant to antidepressants. Akathisia can occur early in treatment with brexpiprazole, as can minor weight gain and prolactin elevation. Indirect data extrapolations from pivotal studies suggest that brexpiprazole and aripiprazole have comparable efficacy but brexpiprazole may cause less akathisia. Like aripiprazole, brexpiprazole has been approved in the USA for use in schizophrenia and antidepressant-resistant depression. Although much more clinical experience is needed, brexpiprazole appears to be distinct from aripiprazole and a promising new 'metabolically-friendly' antipsychotic option for treatment of psychoses and mood disorders.Copyright © 2017, © The Royal Australian and New Zealand College of Psychiatrists 2017.

Objectives: Switching between different antipsychotic therapies is a frequent occurrence in the management of patients with schizophrenia and other psychotic disorders. This paper provides a review of the principles of antipsychotic switching and discusses pharmacological principles underlying adverse events that occur while switching olanzapine to another antipsychotic medication. It offers suggestions for management of switch-associated adverse events in clinical settings. Conclusion(s): Few publications explore olanzapine switch-related adverse events, the underlying pharmacological principles and appropriate switching strategies to minimise the risk of adverse events. There is still a need for further studies to verify existing knowledge and assist in the development of 'gold standard' guidelines that outline appropriate switching strategies and duration of the switching process to reduce and avoid adverse events.Copyright © The Royal Australian and New Zealand College of Psychiatrists 2018.

Objectives: Brexpiprazole is a new dopamine partial agonist antipsychotic in the same class as aripiprazole. This paper will briefly review brexpiprazole and compare it with aripiprazole. Conclusion(s): Brexpiprazole and aripiprazole are both partial agonists at dopamine D2, and serotonin 5-HT1A and antagonists at serotonin 5-HT2A and noradrenergic alpha1B receptors. However, the two drugs are significantly different in potencies at various receptors; neurochemical profiles predict that brexpiprazole may be comparable with aripiprazole in its antipsychotic efficacy but may cause less akathisia, extrapyramidal side effects (EPS) and activation. In pivotal trials brexpiprazole demonstrated antipsychotic efficacy in short and long-term studies; it was also found to be an effective adjunct in patients with major depression resistant to antidepressants. Akathisia can occur early in treatment with brexpiprazole, as can minor weight gain and prolactin elevation. Indirect data extrapolations from pivotal studies suggest that brexpiprazole and aripiprazole have comparable efficacy but brexpiprazole may cause less akathisia. Like aripiprazole, brexpiprazole has been approved in the USA for use in schizophrenia and antidepressant-resistant depression. Although much more clinical experience is needed, brexpiprazole appears to be distinct from aripiprazole and a promising new 'metabolically-friendly' antipsychotic option for treatment of psychoses and mood disorders.Copyright © 2017, © The Royal Australian and New Zealand College of Psychiatrists 2017.

Objectives: Switching between different antipsychotic therapies is a frequent occurrence in the management of patients with schizophrenia and other psychotic disorders. This paper provides a review of the principles of antipsychotic switching and discusses pharmacological principles underlying adverse events that occur while switching olanzapine to another antipsychotic medication. It offers suggestions for management of switch-associated adverse events in clinical settings. Conclusion(s): Few publications explore olanzapine switch-related adverse events, the underlying pharmacological principles and appropriate switching strategies to minimise the risk of adverse events. There is still a need for further studies to verify existing knowledge and assist in the development of 'gold standard' guidelines that outline appropriate switching strategies and duration of the switching process to reduce and avoid adverse events.Copyright © The Royal Australian and New Zealand College of Psychiatrists 2018.

Background: Second generations antipsychotics (SGA) are frequently used for maintenance treatment in bipolar disorder. We systematically reviewed the efficacy and long-term effects of treatment with SGA, regardless of treatment strategy (SGA administered either as monotherapy or as adjunctive therapy), in comparison to placebo, lithium or valproate. Primary outcomes were relapses (mood episode recurrence) and discontinuation. Method: Clinical studies were identified through database searching in PubMed, Embase, PsychInfo and Cochrane Library and critically appraised based on the Cochrane Handbook. Full data extraction of raw data was performed and analyzed with meta-analyses, and level of evidence graded using GRADE. Only randomized controlled studies (RCT) and observational studies were included, with a minimum follow-up of 6 months. Comparators used were restricted to placebo, lithium, valproate or other anti-epileptic drugs. Results: We identified 15 RCTs on SGA in bipolar disorder with follow-up-time of 6 months up to 2 years, and one observational study reporting long-term effects of up to 4 years. A total of 6142 patients were included in the randomized trials. No long-term RCTs beyond 2 years follow-up was identified. All RCTs except for one included patients with bipolar disorder type I only. All RCTs except for two included patients pre-stabilized on the drug under investigation prior to randomization (enrichment design). For SGA as adjunctive therapy to lithium or valproate, meta-analyses showed that treatment with either aripiprazole (RR: 0.65, 95% CI 0.50-0.85), quetiapine (RR: 0.38, 95% CI 0.32-0.46) or ziprasidone (RR: 0.62, 95% CI 0.40-0.96) reduced the overall risk of relapses in patients that had responded during the stabilization phase. Adjunctive therapy with quetiapine was the only drug that reduced both manic and depressive episodes. For SGA as monotherapy, only quetiapine was shown to be better than lithium/ valproate for both manic and depress

Objective: IR-quetiapine overdose is well characterised and this formulation has been available in Australia since 2008. There are no studies comparing toxicity after XR and IR quetiapine overdose. This study compares time course and severity of toxicity of XR and IR quetiapine overdose. Method(s): A retrospective analysis of toxicology consultations from July 2013 to April 2016 was performed. Information extracted included demographics, ingestion, type (IR, XR, mixed formulation, dose, tablet count, time to presentation, co-ingestants), lowest Glasgow Coma Scale (GCS), time to lowest GCS, fastest pulse, lowest systolic BP, time to recovery from sedation, frequency and intubation duration. Result(s): There were 256 presentations in 210 patients comprising females 67% (n = 141), median age 31 years (IQR 23-43). Median quetiapine dose overall was 2 g (IQR 1-5). Sedating co-ingestants were ingested in 61%. Comparison of IR (n = 43) and XR (n = 23) overdoses without sedating co-ingestants revealed no significant difference in age or gender. Median ingested dose was greater for the XR formulation (5.7 g versus 1.75 g, p = .004), as was median tablet strength ingested (XR 200 mg versus IR 100 mg, p < .001). However, median ingested tablet count was similar (30). Median lowest GCS (XR 12.5 versus IR 13) and peak pulse (XR 122 bpm versus IR 118 bpm) were similar. Median time to lowest GCS was longer for XR (7 hours [IQR 4.9-11] versus 3.8 hours [IQR 2.4-5.7], p < .001). Median time to peak pulse was greater for XR (9 hours [IQR 3-12] versus 2.5 hours [IQR 1.5-5], p = .01). Median time to recovery from sedation was longer for XR (20 hours [IQR 12-39] versus 12 hours [IQR 5.5-22], p < .05). Median intubation duration was longer for XR, (47 hours versus 17 hours, p = .04). Inclusion of patients taking sedating co-ingestants resulted in loss of significant differences in time to peak sedation, recovery from sedation and the duration of intubation between groups. Conclusion(s)

Objective: IR-quetiapine overdose is well characterised and this formulation has been available in Australia since 2008. There are no studies comparing toxicity after XR and IR quetiapine overdose. This study compares time course and severity of toxicity of XR and IR quetiapine overdose. Method(s): A retrospective analysis of toxicology consultations from July 2013 to April 2016 was performed. Information extracted included demographics, ingestion, type (IR, XR, mixed formulation, dose, tablet count, time to presentation, co-ingestants), lowest Glasgow Coma Scale (GCS), time to lowest GCS, fastest pulse, lowest systolic BP, time to recovery from sedation, frequency and intubation duration. Result(s): There were 256 presentations in 210 patients comprising females 67% (n = 141), median age 31 years (IQR 23-43). Median quetiapine dose overall was 2 g (IQR 1-5). Sedating co-ingestants were ingested in 61%. Comparison of IR (n = 43) and XR (n = 23) overdoses without sedating co-ingestants revealed no significant difference in age or gender. Median ingested dose was greater for the XR formulation (5.7 g versus 1.75 g, p = .004), as was median tablet strength ingested (XR 200 mg versus IR 100 mg, p < .001). However, median ingested tablet count was similar (30). Median lowest GCS (XR 12.5 versus IR 13) and peak pulse (XR 122 bpm versus IR 118 bpm) were similar. Median time to lowest GCS was longer for XR (7 hours [IQR 4.9-11] versus 3.8 hours [IQR 2.4-5.7], p < .001). Median time to peak pulse was greater for XR (9 hours [IQR 3-12] versus 2.5 hours [IQR 1.5-5], p = .01). Median time to recovery from sedation was longer for XR (20 hours [IQR 12-39] versus 12 hours [IQR 5.5-22], p < .05). Median intubation duration was longer for XR, (47 hours versus 17 hours, p = .04). Inclusion of patients taking sedating co-ingestants resulted in loss of significant differences in time to peak sedation, recovery from sedation and the duration of intubation between groups. Conclusion(s)

English: The manifestation of disseminated cryptococcal infection in HIV-infected individual is a life-threatening infection, with 70% mortality rate in sub-Saharan Africa. People are dying because of the complications around the management. Thus, there is a need for alternative drugs for better management of HIV-associated cryptococcal infection. This thesis successfully demonstrated in vitro anti-cryptococcus activity of: 1) anti-inflammatory drugs (aspirin and ibuprofen), 2) aspirinate-metal complex (CAS), and 3) anti-psychotic drugs (quetiapine and olanzapine). In this thesis, EUCAST guidelines were followed closely and this provides a sense of effectiveness, which is very important for improving patient outcomes. Chapter 2 focused on repurposing aspirin and ibuprofen as alternative anti-cryptococcal drugs. The major findings from this part of the thesis show that, all the tested fungal strains revealed a dose dependent response profile towards aspirin and ibuprofen. Compared to aspirin, ibuprofen exerts greater antimicrobial action. More importantly, the MICs of both drugs did not negatively affect the functioning of macrophages - rather they enhanced the phagocytic capability of macrophages to internalize more cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B at lower concentrations than individual concentrations tested. Our findings revealed the mode of action employed by aspirin and ibuprofen which is via oxidative damage. Chapter 3 focused on a derivative of aspirin viz. copper acyl salicylate (CAS). CAS possess anti-fungal activity against cryptococcal cells and acted in synergy with fluconazole and amphotericin B at lower concentrations than their individual concentrations tested. CAS also kills cells via reactive oxygen species (ROS)-mediated membrane damage. The effect of CAS did not negatively affect macrophages but rather enhance their phagocytic function. Comparing with aspirin, CAS led to more growth, Afrikaans: Die verskeinsel van verspreide Cryptococcus infeksie in MIV-besmette individue is 'n lewensgevaarlike infeksie, met ‘n sterftesyfer van 70% in sub-Sahara Afrika. Mense sterf as gevolg van komplikasies rondom die bestuur. So, daar is 'n behoefte aan alternatiewe medisyne vir beter bestuur van MIV-verwante krypto infeksie. Hierdie proefskrif het suksesvol in vitro anti-Cryptococcus aktiwiteit van: 1) anti-inflammatoriese middels (aspirien en ibuprofen), 2) aspirinaat-metaalkomplekse (KAS), en 3) anti-psigotiese middels (quetiapien en olanzapien) gedemonstreer. In hierdie proefskrif is EUCAST- riglyne gebruik wat ʼn gevoel van doeltreffendheid daarstel, wat baie belangrik is vir die verbetering van die pasiëntuitkomste. Hoofstuk 2 fokus op heraanwending van aspirien en ibuprofen as alternatiewe anti-Cryptococcus middels. Die belangrikste bevindings van hierdie deel van die proefskrif toon dat, al die getoetse gisstamme 'n dosis afhanklik reaksieprofiel teenoor aspirien en ibuprofen vertoon het. In vergelyking met aspirien, het ibuprofen ‘n groter antimikrobiese aksie uitgeoefen. Nog belangriker, die minimum inhiberende konsentrasie (MIK) van beide middels het die funksionering van makrofage nie negatief beïnvloed nie - eerder versterk hulle die fagositiese vermoë van makrofage om meer Cryptococcus selle te internaliseer. Dit is ook aangetoon dat ibuprofen in sinergie met flukonasool en amfoterisien B optree, teen laer konsentrasies as getoetste individuele konsentrasies. Ons bevindinge het getoon dat die antimikorobiese werking van aspirien en ibuprofen is via oksidatiewe skade. Hoofstuk 3 fokus op 'n afgeleide van aspirien nl. koper asielsalisilaat (KAS). KAS besit anti-fungale aktiwiteit teen Cryptococcus selle en tree op in sinergie met flukonasool en amfoterisien B teen laer konsentrasies as hul individuele getoetste konsentrasies. KAS dood ook selle via membraanskade a.g.v. reaktiewe suurstof spesies (RSS). Die effek van KAS het nie 'n negatiewe invloed, National Research Foundation (NRF)

Background Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2 receptors than for serotonergic 5-HT2A receptors, on electrophysiological parameters of attention was investigated in a group of antipsychotic-naïve, first-episode schizophrenia patients compared with a group of age- and gender-matched healthy controls. Method A total of 34 first-episode, antipsychotic-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow-up, whereas controls received no treatment. Results Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only ameliorated in patients treated with above median dosages of quetiapine. Patients had lower P3B amplitude, yet showed similar levels of processing negativity and N100 amplitude compared with healthy controls, both at baseline and follow-up. Conclusions The results indicate that deficits in MMN, P200 and P3B amplitude are present at early stages of schizophrenia, although depending on the paradigm used. Furthermore, the results indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits, and only in those subjects on higher dosages.

Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported in the European Summary of Product Characteristics (SPCs). The ADE report database at Danish Medicines Agency was searched for all quetiapine ADRs involving individuals (<18 years) in the period 1997–2015. Fifteen ADE case reports were retrieved, scrutinized, and categorized. The average age was 14.8 years (range 10–17 years) and six patients were boys. The main reported ADEs were (i) endocrine, for example, hyperprolactinemia and hyperthyroidism, (ii) cardiac, for example, tachycardia and QT prolongation, (iii) neurological, for example, seizures and cerebral hemorrhage, and (iv) psychiatric, for example, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.Copyright © 2015 The British Pharmacological Society.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.Copyright © 2015 The British Pharmacological Society.

Priapism is rarely related to use of non-erectile related medications. The objective was to educate about the multiple possible causes of priapism and to provide treatment recommendations for the different types of priapism. We present the case of a 43 year-old African American male with a history of schizoaffective disorder who presented to our emergency department multiple times over a three year period with priapism, each episode related to the ingestion of quetiapine. Following penile aspiration and intercavernosal injection of phenylephrine, this patient had resolution of his priapism. This case demonstrates an unusual case of recurrent priapism. [West J Emerg Med. 2014;15(1):114–116.]

Background: A proportion of deliberate self-poisoning (DSP) patients present repeatedly to the emergency department (ED). Understanding the characteristics of frequent DSP patients and their presentation is a first step to implementing interventions that are designed to prevent repeated self-poisoning. Method(s): All DSP presentations to three networked Australian ED's were retrospectively identified from the ED electronic medical record and hospital scanned medical records for 2011. Demographics, types of drugs ingested, emergency department length of stay and disposition for the repeat DSP presenters were extracted and compared to those who presented once with DSP in a one year period. Logistic regression was used to analyse repeat versus single DSP data. Result(s): The study determined 755 single presenters and 93 repeat DSP presenters. The repeat presenters contributed to 321 DSP presentations. They were more likely to be unemployed (61.0% versus 39.9%, p = 0.008) and have a psychiatric illness compared to single presenters (36.6% versus 15.5%, p < 0.001). Repeat presenters were less likely to receive a toxicology consultation (11.5% versus 27.3%, p < 0.001) and were more likely to abscond from the ED (7.5% versus 3.4%, p = 0.004). Repeat presenters were more likely to ingest paracetamol and antipsychotics than single presenters. The defined daily dose for the most common antipsychotic ingested, quetiapine, was less in the repeat presenter group (median 1.9 [IQR: 1.3-3.5]) compared with the single presenter group (4 [1.4-9.5]), (OR 0.85, 95% CI 0.74-0.99). Conclusion(s): Patients who present repeatedly to the ED with DSP have pre-existing disadvantages, with increased likelihood of being unemployed and having a mental illness. These patients are also more likely to have health service inequities given the greater likelihood to abscond from the ED and lower likelihood of receiving toxicology consultation for their DSP. Early recognition of repeat DSP patients in

Background: A proportion of deliberate self-poisoning (DSP) patients present repeatedly to the emergency department (ED). Understanding the characteristics of frequent DSP patients and their presentation is a first step to implementing interventions that are designed to prevent repeated self-poisoning. Method(s): All DSP presentations to three networked Australian ED's were retrospectively identified from the ED electronic medical record and hospital scanned medical records for 2011. Demographics, types of drugs ingested, emergency department length of stay and disposition for the repeat DSP presenters were extracted and compared to those who presented once with DSP in a one year period. Logistic regression was used to analyse repeat versus single DSP data. Result(s): The study determined 755 single presenters and 93 repeat DSP presenters. The repeat presenters contributed to 321 DSP presentations. They were more likely to be unemployed (61.0% versus 39.9%, p = 0.008) and have a psychiatric illness compared to single presenters (36.6% versus 15.5%, p < 0.001). Repeat presenters were less likely to receive a toxicology consultation (11.5% versus 27.3%, p < 0.001) and were more likely to abscond from the ED (7.5% versus 3.4%, p = 0.004). Repeat presenters were more likely to ingest paracetamol and antipsychotics than single presenters. The defined daily dose for the most common antipsychotic ingested, quetiapine, was less in the repeat presenter group (median 1.9 [IQR: 1.3-3.5]) compared with the single presenter group (4 [1.4-9.5]), (OR 0.85, 95% CI 0.74-0.99). Conclusion(s): Patients who present repeatedly to the ED with DSP have pre-existing disadvantages, with increased likelihood of being unemployed and having a mental illness. These patients are also more likely to have health service inequities given the greater likelihood to abscond from the ED and lower likelihood of receiving toxicology consultation for their DSP. Early recognition of repeat DSP patients in

Priapism is rarely related to use of non-erectile related medications. The objective was to educate about the multiple possible causes of priapism and to provide treatment recommendations for the different types of priapism. We present the case of a 43 year-old African American male with a history of schizoaffective disorder who presented to our emergency department multiple times over a three year period with priapism, each episode related to the ingestion of quetiapine. Following penile aspiration and intercavernosal injection of phenylephrine, this patient had resolution of his priapism. This case demonstrates an unusual case of recurrent priapism. [West J Emerg Med. 2014;15(1):114–116.]

Objective: Methylene blue (MetBlue) inhibits nitric oxide synthase and guanylate cyclase as well as scavenging endothelial nitric oxide, decreasing vasodilation and increasing responsiveness to vasopressors. It is reported to improve haemodynamics in vasoplegic shock from various causes including septicaemia1 and post-cardiac surgery2. Reports of use in overdose are limited.3 We describe the use of MetBlue to treat a case of refractory vasoplegic shock following quetiapine poisoning. Case report: A 41 year-old male presented following reported ingestion of 18 g extended-release quetiapine, 10 g controlledrelease carbamazepine, 240 mg fluoxetine, 35 g enteric-coated sodium valproate, 375 mg oxazepam. He was comatose, intubated on presentation. Progressive hypotension developed. Electrocardiogram (ECG) revealed sinus rhythm, rate 82 bpm, QRS 120 msec, QT-interval 536 msec. Echocardiogram revealed a hyperdynamic left ventricle, suggesting vasoplegic shock. The patient remained hypotensive despite intravenous fluid-boluses, escalating infusion of metaraminol, noradrenaline and vasopressin. Hypotension was made worse after a single-dose of intravenous adrenaline (100 micrograms) with systolic blood pressure falling to 50 mmHg. Arterial blood gas revealed worsening metabolic acidaemia and rising lactate (peak 13 mmol/L). At this point, MetBlue was administered as loading-dose of 1.5 mg/kg and continuous infusion (1.5 mg/kg/h for 12 hours, then 0.75 mg/kg/h for 12 hours). Rapid improvement in haemodynamic parameters and weaning of vasopressors resulted in the hour following the loading-dose. Serum quetiapine concentration was 18,600 ng/mL (30-160 ng/mL), collected at time of peak toxicity. Serum valproate concentration peaked at the same time and was 1221 micromol/L (300-700 micromol/L). Serum carbamazepine concentration was in the therapeutic range. Conclusion(s): Severe quetiapine poisoning produces hypotension primarily from alpha-adrenoreceptor antagonism. Worsening hy

Objective: Methylene blue (MetBlue) inhibits nitric oxide synthase and guanylate cyclase as well as scavenging endothelial nitric oxide, decreasing vasodilation and increasing responsiveness to vasopressors. It is reported to improve haemodynamics in vasoplegic shock from various causes including septicaemia1 and post-cardiac surgery2. Reports of use in overdose are limited.3 We describe the use of MetBlue to treat a case of refractory vasoplegic shock following quetiapine poisoning. Case report: A 41 year-old male presented following reported ingestion of 18 g extended-release quetiapine, 10 g controlledrelease carbamazepine, 240 mg fluoxetine, 35 g enteric-coated sodium valproate, 375 mg oxazepam. He was comatose, intubated on presentation. Progressive hypotension developed. Electrocardiogram (ECG) revealed sinus rhythm, rate 82 bpm, QRS 120 msec, QT-interval 536 msec. Echocardiogram revealed a hyperdynamic left ventricle, suggesting vasoplegic shock. The patient remained hypotensive despite intravenous fluid-boluses, escalating infusion of metaraminol, noradrenaline and vasopressin. Hypotension was made worse after a single-dose of intravenous adrenaline (100 micrograms) with systolic blood pressure falling to 50 mmHg. Arterial blood gas revealed worsening metabolic acidaemia and rising lactate (peak 13 mmol/L). At this point, MetBlue was administered as loading-dose of 1.5 mg/kg and continuous infusion (1.5 mg/kg/h for 12 hours, then 0.75 mg/kg/h for 12 hours). Rapid improvement in haemodynamic parameters and weaning of vasopressors resulted in the hour following the loading-dose. Serum quetiapine concentration was 18,600 ng/mL (30-160 ng/mL), collected at time of peak toxicity. Serum valproate concentration peaked at the same time and was 1221 micromol/L (300-700 micromol/L). Serum carbamazepine concentration was in the therapeutic range. Conclusion(s): Severe quetiapine poisoning produces hypotension primarily from alpha-adrenoreceptor antagonism. Worsening hy

Background Despite being present in up to 1% of the population, few controlled trials have examined the efficacy of treatments for bipolar II depression. Pooled data are presented from four placebo-controlled studies (BOLDER I [5077US/0049] and II [D1447C00135]; EMBOLDEN I [D1447C00001] and II [D1447C00134]) that evaluated the efficacy of quetiapine monotherapy for depressive episodes in patients with bipolar II disorder. Methods All studies included an 8-week, double-blind treatment phase in which patients were randomly assigned to treatment with quetiapine 300 mg/day, quetiapine 600 mg/day, or placebo. Outcome measures included the change from baseline in MADRS total score at week 8, effect sizes, and MADRS response and remission rates. Results and discussion Improvements in mean MADRS total scores from baseline to week 8 were significantly greater with quetiapine 300 and 600 mg/day (−15.58 [n = 283] and −14.88 [n = 289]; p < 0.001) compared with placebo (−11.61 [n = 204]). The MADRS effect sizes were 0.44 for quetiapine 300 mg/day and 0.47 for 600 mg/day (p < 0.001 vs placebo). Significantly higher proportions of patients receiving quetiapine, at both doses, than placebo-treated patients achieved response and remission at week 8 (p < 0.01). Common adverse events associated with quetiapine (both doses) included dry mouth, somnolence, sedation, dizziness, and headache. Rates of mania and hypomania were similar for quetiapine and placebo. Quetiapine monotherapy demonstrated significant efficacy compared with placebo and was generally well tolerated in the treatment of bipolar II depression.

Pharmacological intervention using antipsychotic agents is the cornerstone of treatment in schizophrenia. Polypharmacy and the use of higher doses is often practised in the hope of getting better symptom control in multi-episode, chronically unwell, people with schizophrenia. However, these regimes often pose unacceptable and at times dangerous risks. The current review examines the factors that influence dosing and argues that optimization is transient and needs ongoing consideration throughout the course of the illness. What is defined as 'the optimal dose' changes over the course of the illness and this should be reflected in treatment. The evidence presented in the current paper suggests that given the negative symptoms associated with neuroleptic medication, dosage should be discussed as part of the case review process and dosage should be systematically reduced as part of the standard treatment protocol. A case-study is presented of a patient who had her dosage of clozapine reduced and the subsequent health and lifestyle benefits from this reduction. We argue that the focus needs to be shifted away from the specific aim of treatment of psychotic symptoms to a more holistic view of treatment that incorporates function and psychosocial function as a measure of improvement. © 2010 Institute of Psychiatry.

Pharmacological intervention using antipsychotic agents is the cornerstone of treatment in schizophrenia. Polypharmacy and the use of higher doses is often practised in the hope of getting better symptom control in multi-episode, chronically unwell, people with schizophrenia. However, these regimes often pose unacceptable and at times dangerous risks. The current review examines the factors that influence dosing and argues that optimization is transient and needs ongoing consideration throughout the course of the illness. What is defined as 'the optimal dose' changes over the course of the illness and this should be reflected in treatment. The evidence presented in the current paper suggests that given the negative symptoms associated with neuroleptic medication, dosage should be discussed as part of the case review process and dosage should be systematically reduced as part of the standard treatment protocol. A case-study is presented of a patient who had her dosage of clozapine reduced and the subsequent health and lifestyle benefits from this reduction. We argue that the focus needs to be shifted away from the specific aim of treatment of psychotic symptoms to a more holistic view of treatment that incorporates function and psychosocial function as a measure of improvement. © 2010 Institute of Psychiatry.

Children and adolescents who develop schizophrenia tend to have greater symptom severity than adults who develop the illness. Since the brain continues to mature into early adulthood, developmental differences in brain structure and function may provide clues to the underlying neurobiology of schizophrenia. With an emerging body of evidence supporting disrupted connectivity contributing to the underlying pathophysiology of schizophrenia, it was our goal to assess differences in functional connectivity in children and adolescents who develop schizophrenia. Participants included a total of 28 children and adolescents (14 patients with schizophrenia and 14 age- and gender-matched controls). All subjects underwent a functional magnetic resonance imaging scan involving a modified Sternberg Item Recognition Paradigm with 3 working memory (WkM) loads. Patients had poorer performance at all 3 WkM loads without a load by diagnosis interaction. Functional imaging results demonstrated 3 specific brain networks disrupted in children and adolescents with schizophrenia. These networks include 1) the anterior cingulate and the temporal lobes, bilaterally; 2) the cerebellum with subcortical regions; and 3) the occipital lobe and the cerebellum. Patients with early-onset schizophrenia demonstrate abnormal functional connectivity in networks involving limbic, temporal lobe, cerebellum, and early visual processing streams.

Objective: To assess the efficacy and safety of quetiapine and haloperidol in the treatment of schizophrenia and the differences in adverse effects of them. Methods: Meta analysis on the 14 papers about efficacy and safety of quetiapine and haloperidol in the treatment of schizophrenia was performed, and the total effective rate, cure ratative, obvious effective rate and adverse effects were evaluated. Results: Circled digit 1 Haloperidol and quetiapine had similar total effective rate (P = 0.76); Circled digit 2 there was significant difference of curative rate between haloperidol and quetiapine in treatment of schizophrenia (P = 0. 04); Circled digit 3 Compared with haloperidol, quetiapine had a higher obvious effective rate (P = 0.006); Circled digit 4 the incidence rates of akathisia, myotonia, dry mouth etc in quetiapine group were lower than those in haloperidol group (P<0.05). Conclusion: Quetiapine is better than haloperidol on the cure rate and obvious effective rate in the treatment of schizophrenia. Further, quetiapine has less extrapyramidal reactions.

Objective: To assess the efficacy and safety of quetiapine and haloperidol in the treatment of schizophrenia and the differences in adverse effects of them. Methods: Meta analysis on the 14 papers about efficacy and safety of quetiapine and haloperidol in the treatment of schizophrenia was performed, and the total effective rate, cure ratative, obvious effective rate and adverse effects were evaluated. Results: Circled digit 1 Haloperidol and quetiapine had similar total effective rate (P = 0.76); Circled digit 2 there was significant difference of curative rate between haloperidol and quetiapine in treatment of schizophrenia (P = 0. 04); Circled digit 3 Compared with haloperidol, quetiapine had a higher obvious effective rate (P = 0.006); Circled digit 4 the incidence rates of akathisia, myotonia, dry mouth etc in quetiapine group were lower than those in haloperidol group (P<0.05). Conclusion: Quetiapine is better than haloperidol on the cure rate and obvious effective rate in the treatment of schizophrenia. Further, quetiapine has less extrapyramidal reactions.

Quetiapine is a second generation antipsychotic that shows affinity for various neurotransmitter receptors: specifically the D1 and D2 dopamine receptor, the alpha-1 and alpha-2 adrenergic receptor, and 5-HT1A and 5-HT2 serotonin receptor subtypes are antagonized. In the bipolar spectrum disorders quetiapine is approved for the treatment of acute manic and mixed episodes associated with bipolar I disorder. It is also approved for the treatment of acute bipolar depressive episodes and as adjunctive maintenance therapy of bipolar I disorder with lithium or valproate. In a previous study we reported the high frequency of association between bipolar disorder and behavioural addictions and the correlation with high level of impulsivity and specific temperamental and character dimensions. We underlined that the assessment of behavioural addictions in bipolar disorder patients may have a direct impact on the choice of pharmacological and psycho-educative interventions aimed at reducing harmful behaviours and the risk of relapses. The present case report deals with the potential use of quetiapine as add-on treatment for bipolar I disorder with comorbid compulsive buying and physical exercise addiction.

Objective: To assess the efficacy and safety of quetiapine and haloperidol in the treatment of schizophrenia and the differences in adverse effects of them. Methods: Meta analysis on the 14 papers about efficacy and safety of quetiapine and haloperidol in the treatment of schizophrenia was performed, and the total effective rate, cure ratative, obvious effective rate and adverse effects were evaluated. Results: Circled digit 1 Haloperidol and quetiapine had similar total effective rate (P = 0.76); Circled digit 2 there was significant difference of curative rate between haloperidol and quetiapine in treatment of schizophrenia (P = 0. 04); Circled digit 3 Compared with haloperidol, quetiapine had a higher obvious effective rate (P = 0.006); Circled digit 4 the incidence rates of akathisia, myotonia, dry mouth etc in quetiapine group were lower than those in haloperidol group (P<0.05). Conclusion: Quetiapine is better than haloperidol on the cure rate and obvious effective rate in the treatment of schizophrenia. Further, quetiapine has less extrapyramidal reactions.

An altered regulation of the corticotropin-releasing hormone (CRH) system in the CNS is consistently associated with anxiety and depression; several drugs used to treat CNS disorders modulate--usually in a negative manner--CRH turnover in the brain, and it can be postulated that their effectiveness may be at least in part related to their effects on CRH. This study was aimed to investigate the effects of two atypical antipsychotics also employed in the treatment of bipolar disorders, i.e. quetiapine (QTP) and olanzapine (OLZ), on CRH release from isolated rat brain regions. Acute rat hypothalamic and hippocampal explants were exposed for 1 h to plain medium or medium containing the test drugs, either under baseline conditions or after stimulation of CRH release by veratridine or 56 mM KCl. CRH immunoreactivity present in the incubation medium and in the tissues was assessed by radioimmunoassay. QTP 10 microM but not OLZ inhibited baseline CRH secretion from the hypothalamus; neither drug affected basal CRH release from the hippocampus. Both QTP and OLZ, 1 and 10 microM, inhibited veratridine- or K(+)-stimulated CRH release from the hypothalamus, whereas OLZ only, when given at 10 microM, was able to inhibit stimulated CRH release from the hippocampus. In conclusion, two widely used atypical antipsychotics, QTP and OLZ are able to acutely reduce the release of CRH from isolated rat hypothalami and hippocampi.

Background: With the advent of newer antipsychotic drugs, side effects such as sexual dysfunction have been a major contributor toward treatment compliance. There are only a few studies that have compared different atypical antipsychotic agents regarding sexual dysfunction. We have not come across any data in this area on Indian population. Aims: To determine and compare the frequency of sexual dysfunction associated with risperidone, olanzapine, and quetiapine, among patients with clinically stable schizophrenia. Settings and Design: It is a cross-sectional hospital-based study. The subjects were recruited for the study by the purposive sampling technique. Materials and Methods: The total sample size was 102, consisting of 25 each in the quetiapine and risperidone groups, 22 in the olanzapine group, and 30 healthy volunteers. A Brief Psychiatric Rating Scale and Sexual Functioning Questionnaire (SFQ) were administered. The Kruskal Wallis test was used to compare the variables in the demographic data and the mean chlorpromazine equivalent doses of the study groups. To analyze the sexual dysfunction, the mean scores on all the domains of sexual functioning in SFQ were compared across the study groups using the Chi square test, for proportions. Results and Conclusion: Twenty-three percent of the healthy volunteers had some impairment in one or more domains of sexual functioning. For the medication groups this was 96, 88, and 90%, respectively for risperidone, quetiapine, and olanzapine. However, there was statistically no significant difference across the study groups although it was relatively less with quetiapine.

Background: With the advent of newer antipsychotic drugs, side effects such as sexual dysfunction have been a major contributor toward treatment compliance. There are only a few studies that have compared different atypical antipsychotic agents regarding sexual dysfunction. We have not come across any data in this area on Indian population. Aims: To determine and compare the frequency of sexual dysfunction associated with risperidone, olanzapine, and quetiapine, among patients with clinically stable schizophrenia. Settings and Design: It is a cross-sectional hospital-based study. The subjects were recruited for the study by the purposive sampling technique. Materials and Methods: The total sample size was 102, consisting of 25 each in the quetiapine and risperidone groups, 22 in the olanzapine group, and 30 healthy volunteers. A Brief Psychiatric Rating Scale and Sexual Functioning Questionnaire (SFQ) were administered. The Kruskal Wallis test was used to compare the variables in the demographic data and the mean chlorpromazine equivalent doses of the study groups. To analyze the sexual dysfunction, the mean scores on all the domains of sexual functioning in SFQ were compared across the study groups using the Chi square test, for proportions. Results and Conclusion: Twenty-three percent of the healthy volunteers had some impairment in one or more domains of sexual functioning. For the medication groups this was 96, 88, and 90%, respectively for risperidone, quetiapine, and olanzapine. However, there was statistically no significant difference across the study groups although it was relatively less with quetiapine.

Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.

A green process for the synthesis of 11-{4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl}dibenzo[b,f][1,4]thiazepine by the reaction of 11-(1-piperazinyl)dibenzo[b,f][1,4]thiazepine or its dihydrochloride salt with 2-(2-chloroethoxy)ethanol in the presence of an inorganic base and water is reported (conversion 99.9 % in a short time and without any impurities). The metal halides and phase transfer catalyst increase the rate of reaction, especially in water as the solvent.

Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.

New-Onset Diabetes Mellitus among Parkinsonian Patients Treated with Long-term Quetiapine, non disponibile

New-Onset Diabetes Mellitus among Parkinsonian Patients Treated with Long-term Quetiapine, non disponibile

Aims Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high-risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability. Methods Twenty-eight subjects, after a detoxification period, were orally treated with flexible doses of quetiapine for 16 weeks. At each assessment patients were evaluated through the Obsessive Compulsive Drinking Scale (OCDS), the Visual Analogue Scale (VAS) for craving, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI) scale. Results Forty-three percent of patients remained totally alcohol free, 32% patients relapsed, with an average of 15.4 drinking days in the period of the study (112 days) and 25% dropped-out. Significant reductions from baseline to exit were observed in the OCDS, VAS, BPRS, HDRS, and number of drinking days per week. Changes in alcohol craving correlated with psychiatric symptoms as to BPRS and HDRS, with the highest level of correlation evidenced for the HDRS items of insomnia. Discussion In this open-label study, quetiapine decreased alcohol consumption, craving for alcohol, and psychiatric symptoms intensity, maintaining a good level of tolerance. A strength of this study is that the use of quetiapine was not adjunctive with other pharmacological and non-pharmacological treatment. Double-blind placebo-controlled studies are required with a larger study population to confirm these data. In the meantime, for a select group of psychiatric patients, quetiapine may offer some advantages in preventing relapse.

Background: Neuroleptic malignant syndrome (NMS) is an uncommon, but potentially life threatening complication of neuroleptic drugs. In 1960, Delay et al. [Ann Med Psychol 118 (1960) 145-152] described the "syndrome akinétique hypertonique"(hypertonic akinetic syndrome) and its cardinal symptoms: hyperthermia, extrapyramidal symptoms, altered mental status and autonomic dysfunctions. The syndrome often develops after a sudden increase in dose of neuroleptic medication or in states of dehydration. The frequency of NMS with conventional neuroleptic drugs ranges from 0.02 to 3.3%. The pathophysiology of NMS is not clearly understood. It has been suggested that the potential to induce NMS of neuroleptics is parallel to the potency of dopamine blockade in the nigrostriatal tract, mesocortical pathway and hypothalamic nuclei. It is, however, intriguing that NMS may appear with atypical antipsychotics (AA) and especially clozapine (CLZ), which is mainly characterized by its low affinity to D1 and D2 receptors. Objective: The purpose of this study was to review cases of NMS induced by AA agents reported in the literature and to discuss the pathophysiology of this complication. Methods: Cases of NMS related to AA were collected by means of a MEDLINE literature search between January 1986 and June 2005. As key words we used: (NMS and AA), amisulpride (AMS), clozapine (CLZ), olanzapine (OLZ), risperidone (RIS), quetiapine (QTP), ziprazidone (ZPS) and side effects. For the purpose of our review, all cases were critically examined against standard NMS diagnostic criteria according to DSM-IV. Cases involving a coprescription of classical neuroleptics were excluded. Results: Our search yielded 47 cases (eight women, 39 men) of NMS associated with AA meeting DSM-IV criteria. Patients' mean age was 37 years, primary patient diagnoses were schizophrenia (n = 26), schizoaffective disorder (n = 9), bipolar disorder (n = 3), mental retardation (n = 4) and other diagnoses (n = 5). Drugs, SCOPUS: sh.j, info:eu-repo/semantics/published

New-Onset Diabetes Mellitus among Parkinsonian Patients Treated with Long-term Quetiapine, non disponibile

Bipolar disorder has a major deleterious impact on many aspects of a patient's functioning and health-related quality of life. Although the formal measurement of these deficits has been neglected until recently, many well-designed trials now include an assessment of functioning and health-related quality of life using one or more rating scales. This review describes recent developments in the measurement of functioning and health-related quality of life in bipolar disorder, and discusses the evidence that medications that improve symptoms in bipolar disorder also offer clinically relevant benefits in functioning and health-related quality of life. Direct comparisons of the benefits of medications including atypical antipsychotics are problematic due to differences in trial populations, study durations and rating scales. Data from quetiapine trials indicate that this medication offers prompt and sustained improvement of functioning in patients with mania and enhancement of health-related quality of life in patients with bipolar depression, to accompany the significant improvements in mood episodes.

The present study aimed to estimate the incidence of diabetes in general practice patients who were treated with haloperidol, olanzapine, risperidone or quetiapine monotherapy and in subjects who were not exposed to antipsychotics. The design was a retrospective, up to 2 years, cohort study, with age-, sex- and length of observation-matching between subjects who were exposed and not exposed to antipsychotic drugs. Data were taken from the Health Search database, which contains information from 550 Italian general practitioners. Participants comprised 2,071 subjects taking haloperidol, 266 taking olanzapine, 567 taking risperidone and 109 taking quetiapine, in addition to 6,026 age- and sex-matched subjects who were not using antipsychotic drugs during the period of observation. Inclusion was limited to initially non-diabetic and antipsychotic drug-free individuals. The main outcome measure was the incidence of drug-treated diabetes. After age and sex correction by Cox regression analysis, the four groups treated with antipsychotics significantly differed from untreated subjects in hazard ratios for diabetes. The ratios for the haloperidol, olanzapine, risperidone and quetiapine groups were 12.4 (95% confidence interval 6.3-24.5), 20.4 (6.9-60.3), 18.7 (8.2-42.8) and 33.7 (9.2-123.6), respectively, with no significant differences when compared to each other.

Schizophrenia is a group of disorders with a worldwide lifetime prevalence of 0.85%. Thefunctional outcome of the disorder seem stable from the first systematic outcome studies to thepresent day, and vary only with changes in diagnostic criteria. Positron emission tomography (PET) has enabled us to quantify receptor populations and inschizophrenia postsynaptic dopamine receptors have been thoroughly studied by use of 11C-raclopride (RAC). The PET tracer of the dopamine precursor L(β-11C)-DOPA, offers anopportunity of studying presynaptic function of the dopaminergic system. Presynaptic dopamine turnover was studied in twelve patients before antipsychotic treatment and compared to healthy volunteers. Increased dopamine synthesis in the striatum could be demonstrated in the patient group thus confirming a dopaminergic dysregulation in striatum. We could also demonstrate an increase in the dopamine synthesis in medial prefrontal cortex, suggesting alterations in limited areas also in cortex. Antipsychotic drug treatment is often the basis for the treatment of schizophrenia. We have studied quetiapine, an antipsychotic compound. In our PET studies we have found a consistent 45-50% dopamine D2 receptor blockade at time of maximum plasma concentration. The receptorblockade rapidly declined and was not detectable after 26 hours. Clinically no motor side effects was noted at any dose level, and we concluded that quetiapine fulfill stringent criteria for an atypical antipsychotic. Some quetiapine treated patients were PET scanned with RAC and the serotonin and dopamine receptor tracer (methylspiperone, NMSP) using the same dose level ofquetiapine as in the previous study. An dopamine D2 blockade could be determined by use of with11C-raclopride, but not when 11C-NMSP was used as the tracer. This difference may explainvariable data in the literature on the dopamine blocking properties of clozapine, the modelatypical antipsychotic. A novel antipsychotic, risperidone, with a mor

Objective: To describe pharmacological and non-pharmacological practices for delirium, carried out by psychiatry residents and psychiatrists in Colombia. Methods: An anonymous survey was conducted based on the consensus of experts of the Liaison Psychiatr