β_(2) and α_(2) adrenergic receptors mediate the proneurogenic in vitro effects of norquetiapine

Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants,promotes adult hippocampal neurogenesis in preclinical studies.Norquetiapine,the key active metabolite of quetiapine in humans,has a distinctive receptor profile than the parent compound.The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect.At present,no information is available on the effects of norquetiapine on adult neurogenesis.We extensively investigated the activity of quetiapine and norquetiapine on adult murine neural stem/progenitor cells and their progeny.Additionally,selective antagonists for β_(2)/α_(2) adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and norquetiapine effects.We demonstrated that both drugs elicit in vitro proneurogenic effects but also that norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β_(2)/α_(2) adrenergic receptors.Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees(IACUC)at University of Piemonte Orientale,Italy(approval No.1033/2015PR)on September 29,2015.

Comparative effectiveness of quetiapine and haloperidol in delirium:A single blind randomized controlled study

AIM To evaluate the effectiveness of quetiapine and haloperidol in patients of delirium referred to psychiatry consultation liaison services.METHODS The study followed a single blind randomised controlled trial design.Thirty-two patients in the haloperidol group and 31 patients in the quetiapine group were assessed at the baseline and 6 consecutive days.Flexible dosing regimen(haloperidol:0.25-1.25 mg;quetiapine 12.5-75 mg/d) was used.Delirium Rating Scale-Revised-98(DRS-R-98) and mini mental status examination(MMSE) were the primary and secondary efficacy measures respectively.RESULTS Baseline DRS-R-98 severity score and MMSE scores did not differ between the 2 study groups.From baseline to day 6,there was significant reduction in the total DRS-R-98 scores,DRS-R-98 cognitive domain scores,DRS-R-98 non-cognitive domain scores and significant increase in the MMSE scores in both the groups.Both the groups did not differ on any of the assessments in terms of DRS-R98 and MMSE scores.The effectiveness of both the medications was similar in adult and elderly(≥ 60 years) patients.At the end of the trial,68.75% and 67.74% of subjects in the haloperidol and quetiapine group respectively had mean DRS-R-98 scores below 10.By 6th day,12(37.5%) patients in haloperidol group and 9(29.03%) patients in the quetiapine group hadDRS-R98 score of "0" with no significant difference between the two groups(P = 0.47).CONCLUSION Quetiapine is as effective as haloperidol in the management of delirium.

Quetiapine augmentation of prolonged exposure therapy in veterans with PTSD and a history of mild traumatic brain injury: design and methodology of a pilot study

Background: Selective serotonergic reuptake inhibitors(SSRIs) are first-line pharmacologic treatments for patients with posttraumatic stress disorder(PTSD), but must be given over extended period of time before the onset of action. The use of SSRIs in PTSD patients with mild traumatic brain injury(m TBI) is problematic since SSRIs could exacerbate post-concussion syndrome(PCS) symptoms. VA/DOD guidelines identify trauma-focused psychotherapy as the best evidence-based treatment for PTSD, but overall effectiveness is limited by reduced levels of patient engagement and retention. A previous study from this research group suggested that quetiapine monotherapy, but not risperidone or valproate, could increase engagement in trauma-focused psychotherapy.Methods: We report the study protocol of a pilot study funded under the South-Central Mental Illness Research, Education, and Clinical Center pilot study program from the U.S. Department of Veterans Affairs. This randomized, open-label study was designed to evaluate the feasibility of completing a randomized trial of quetiapine vs. treatment as usual to promote patient engagement in PTSD patients with a history of m TBI.Discussion: We expect that the success of this ongoing study should provide us with the preliminary data necessary to design a full-scale randomized trial. Positive efficacy results in a full-scale trial should inform new VA guidelines for clinical practice by showing that quetiapine-related improvements in patient engagement and retention may be the most effective approach to assure that VA resources achieve the best possible outcome for veterans.Trial registration: NCT04280965.

Quetiapine-related acute lung injury:A case report

BACKGROUND Quetiapine,known as a non-classical antipsychotic drug,is frequently used for the treatment of mental diseases,such as schizophrenia,bipolar disorder,and major depressive disorder.Acute lung injury,a rarely reported side effect of quetiapine,is described in this case report.CASE SUMMARY Due to terminal delirium,a 66-year-old man took a large dose of quetiapine and then developed severe pulmonary disease.His symptoms were not resolved after routine treatment,such as antibiotics,diuretic,and supportive therapies.Quetiapine-related acute lung injury was therefore suspected and hormonal therapy was initiated.Subsequently,his symptoms were alleviated and the radiological results improved dramatically.CONCLUSION Our findings in the present report highlight a potential adverse effect of quetiapine,drug-related acute lung injury,which deserves awareness in clinical practice.

A Comparison Study of the Efficacy of Rapid Titration Quetiapine and Haloperidol in Agitated Adults in an Emergency Setting

Objective: Intramuscular (IM) Benzodiazepines and/or Haloperidol alone or with benzodiazepines are frequently used to treat agitation. Based on emerging literature regarding Quetiapine used for the control of anxiety we examined Quetiapine as a possible alternative in selected cases. Methods: This study was a single-blind randomized study comparing Quetiapine PO (300 mg) with a combination of Haloperidol (5 mg), Benztropine mesylate (2 mg) and lorazepam (2 mg) administered IM to treat agitated patients seeking care in a busy psychiatric emergency setting. Male or female patients (18 - 60), deemed by the attending (admitting) psychiatrist to be indicative of agitated and/or aggressive behavior and had a Positive and Negative Syndrome Score-Excited Component (PANSS-EC), as evaluated by the Research Psychiatrist, and total score equal to or greater than 15. Patients deemed competent were randomized into one of the following treatment groups: Quetiapine 300 or Haloperidol 5 mg, benztropine mesylate, or lorazepam given by the IM route. Two scales, PANSS-EC and CGI-C were used to assess patients in the trial. The primary outcome measure PANSS-EC at 2 hours after administration of the medication. Results: Sixty-eight patients were included in the study. There were no significant treatment group differences in baseline condition. There was no significant difference between the two conditions. There was, however, a significant within-group decrease from baseline condition. Conclusion: Finding no significant differences suggests that in general the two treatments were equivalent. To sum up, Quetiapine 300 mg as a single dose appeared safe and effective in agitated patients treated in an ER. The results were similar to a comparison group receiving an intra-muscular combination of Haloperidol, Lorazepam and Benztropine. This study has significant limitations. The study was single blind and the use of a placebo would have strengthened the design but would be considered unethical. The sample size was relatively small and the group of patients who come to the ER may not be representative of the population of patients who visit across the country. And finally it was a select subgroup who made up the study population and who were probably less severely ill than other subjects who came to our ER.

Needs monitoring with quetiapine

To the Editor:We read with great interest regarding the article on "Acute Pancreatitis Associated with Valproate Treatment."By Quan et al^[1] published in your esteemed journal.

Polydipsia, hyponatremia and rhabdomyolysis in schizophrenia: A case report

The prevalence of polydipsia among patients with schizophrenia is 6%-20%. Around 10%-20% of patients with polydipsia may develop hyponatremia and even complicated with rhabdomyolysis. Here we presented a 40-year-old man with schizophrenia, who had received paliperidone 15 mg/d for more than one year, and polydipsia was noted. In Jan, 2014, he developed hyponatremia(Na 113 m Eq/L) with consciousness disturbance. After 3% Na Cl(500 cc/d) intravenous supplement for three days, the hyponatremia was corrected, but rhabdomyolysis developed with a substantial elevation in the level of creatine kinase(CK) to 30505 U/L. After hydration, the CK level gradually decreased to 212 U/L. Both the hyponatremia itself and quick supplementation of Na Cl can cause rhabdomyolysis. If rhabdomyolysis is not recognized, insufficient hydration or water restriction for polydipsiamay further exacerbate the rhabdomyolysis with a lethal risk. In this case, we highlight the possible complication of rhabdomyolysis with polydipsia-induced hyponatremia. In addition to monitoring the serum sodium level, the monitoring of CK is also important; and switching of antipsychotic may improve the polydipsia.