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Objectives Cure for severe depression in elderly patients with psychotic symptoms should consider not only the results of major depression but also the nature of antidepressants and their side effects. Psychiatric disability is higher in patients who have greater deterioration in neurological function. Methods In addition to reviewing antidepressant discontinuation syndrome and depressive disorder, this study describes an elderly woman with mild depression that developed into major depression, related to high suspicion of delirium, diagnosed based on patient history, physical health examination, neurological examinations, family history, and laboratory data, with subsequent treatment plan. Results The treatment results and prognosis indicate that patients with paroxetine antidepressant deactivation may enable early use of low-dose quetiapine with less anticholinergic and extrapyramidal side effects for the treatment of depression in elderly patients with psychotic symptoms. The poor prognostic factors for patients were chronic environmental stress (poverty) and lack of a social support system. Although the patient lived with her children and grandchildren, she rarely received care. Hence, it was not possible to monitor her condition and medication intake. Conclusions The consensus is that the abrupt discontinuation of short half-life selective serotonin reuptake inhibitors (SSRIs), such as paroxetine can be associated with transient symptomatology, much of which is of a serotonergic nature. Psychotic-like symptoms have also been reported in both controlled trials and large patient databases.

A 48-year-old man who is a known case of bipolar disorder was maintaining well on a combination of carbamazepine and quetiapine for 3 years until he developed fever, severe leucopenia and lymphadenopathy, along with significant loss of weight and appetite. A thorough investigation revealed Kikuchi’s disease as a likely histological diagnosis. Carbamazepine was discontinued and quetiapine was titrated for the management of psychiatric symptoms. The patient gradually made good recovery following discontinuation of carbamazepine and the diagnosis of drug-induced myelosuppression was retained. Clinicians need to be aware of the adverse effects of medications being used for long-term prophylaxis and other possible conditions that may change the course of drug effects.

Post-traumatic stress disorder (PTSD), previously known as battle fatigue syndrome or shell shock, is a severe mental disturbance condition that is normally triggered by the experience of some frightening/scary events or trauma where a person undergoes some serious physical or mental harm or threatened. PTSD is a long-life effect of the continuous occurrence of traumatic conditions, leading to the production of feelings of helplessness, intense fear, and horror in the person. There are various examples of events that can cause PTSD, such as physical, mental, or sexual assault at home or working place by others, unexpected death of a loved one, an accidental event, war, or some kind of natural disaster. Treatment of PTSD includes the removal or reduction of these emotional feelings or symptoms with the aim to improve the daily life functioning of a person. Problems which are needed to be considered in case of PTSD like ongoing trauma, abusive or bad relationships. Various drugs which are used for the treatment of PTSD include selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluvoxamine, fluoxetine, etc.); tricyclic antidepressants (amitriptyline and isocarboxazid); mood stabilizers (Divalproex and lamotrigine); atypical antipsychotics (aripiprazole and quetiapine), etc. In this review, we have covered the different risk factors, case studies related to various treatment options with different age group of peoples with PTSD and their effects on them. We have also covered the symptoms and associated disorders which can play a key role in the development of PTSD.

Objective: The youngest children in a classroom have a higher risk of attention-deficit/hyperactivity disorders (ADHDs) and depression than their relatively older peers. However, there has been a lack of research on how relative age is related to second-generation antipsychotic (SGA) medication use. Methods: This study used the Finnish National Prescription Register data and comprised all 669,726 Finnish children and adolescents aged 7-17 in 2018. We extracted data for those who were dispensed SGAs (risperidone, quetiapine, aripiprazole, and olanzapine) and ADHD medication (methylphenidate, atomoxetine, dexamphetamine, and lisdexamfetamine). Odds ratios (OR) and 95% confidence intervals (CI) were calculated for medication dispensed to schoolchildren born from January to April (the relatively oldest), May to August, and September to December (the relatively youngest). Dispensed prescriptions were a proxy for medication use. Results: SGAs were dispensed to 9146 (1.4%) individuals in 2018. Their use was lower among girls aged 12-17 years born from September to December than January to April (OR 0.89; 95% CI 0.83-0.97), with no association between SGA use and birth month among boys. However, younger relative age was associated with combined SGA and ADHD medication, which was used by 2556 (0.4%) of the cohort: 2074 (0.6%) boys and 482 (0.1%) girls. The OR was 1.27 for boys aged 12-17 born from September to December (95% CI 1.10-1.46), compared with January to April. The OR for girls born from May to August was 1.35 (95% CI 1.04-1.76) and from September to December it was 1.33 (95% CI 1.02-1.74), compared with January to April. Conclusions: A novel discovery of this study was that using both SGA and ADHD medication at the age of 12-17 years was more common among the youngest subjects in a school year than their relatively older peers.

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p

Summary Introduction The drugs used to treat psychiatric illnesses are known as antipsychotics. Antipsychotics have a higher incidence of adverse drug reactions including extrapyramidal side effects and several other metabolic disorders. The main objective of the study is to assess the changes in anthropometric parameters of metabolic risk in patients with severe mental disorders initiated with antipsychotic drug therapy. Materials and methods A prospective observational study was carried out in the psychiatric inpatient unit of a tertiary care teaching hospital for eight months. Eligible patients were enrolled and their baseline and follow-up anthropometric measurements such as body weight, body mass index (BMI), fat index, and waist-hip ratio were taken before and after six weeks of therapy. The changes were documented and analyzed. Results and Discussion The most commonly prescribed antipsychotics were olanzapine, clozapine, risperidone and quetiapine. A considerable mean increase in the body weight of 4.5 kg with a mean increase in body mass index of 1.7 kg/m2, percentage body fat of 1.84% and the waist-hip ratio of 0.027 was observed among patients treated with olanzapine. Similarly, patients who were prescribed with clozapine also revealed a significant increase in the mean body weight of 4.7 kg, an increase in BMI of 1.75 kg/m2, 0.07 of waist-hip ratio and a percentage body fat of 1.4%. On analysis, patients treated with quetiapine and risperidone also showed significant changes in the anthropometric parameters. Conclusion The overall comparison and statistical analysis of different anthropometric parameters suggest that the changes observed within the parameters were a result of antipsychotic drug therapy.

Background and Objectives In clinical trials, the safety of drugs is summarized by the incidence of adverse events, while post-marketing reporting systems use disproportionate reporting of adverse drug reactions. Here, we propose a method to evaluate the novelty of a safety profile of a drug in a new class (in clinical trials), against that of those already on the market (using pharmacovigilance data). Methods Through Bayesian disproportionality analyses of the US Food and Drug Administration Adverse Event Reporting System (FAERS) data, we identified and ranked Preferred Terms for a pool of 30 antipsychotics. Adverse event rates in randomized, double-blind, placebo-controlled schizophrenia clinical trials were summarized by their class specificity. One study (N = 245) of the trace amine-associated receptor 1 (TAAR1) agonist ulotaront (SEP-363856) was compared with five studies of dopamine D2 receptor-based antipsychotics lurasidone (N = 1041), quetiapine (N = 119), olanzapine (N = 122), and placebo (N = 504). Results In clinical trials of antipsychotics, cumulative rates for adverse events at and above a threshold of disproportional reporting (Empirical Bayes Geometric Mean 50 > 3 in FAERS) were 52%, 42%, and 60% for lurasidone, quetiapine, and olanzapine, respectively, indicating that over half of the adverse events reported in clinical trials of an atypical antipsychotic are class-specific risks. In contrast, in the clinical trial of ulotaront, the cumulative rate was 23%, indicating a lower rate of antipsychotic class-specific risk. Conclusions These results demonstrate a novel approach to summarize adverse events in clinical trials, where the cumulative burden of class-specific risks describes the emerging safety profile of a new drug in clinical development, relative to reactions anticipated for drugs in an established pharmacological class. ClinicalTrials.gov Identifiers NCT0296938, NCT00088634, NCT00549718, NCT00615433, NCT00790192. Supplementary Information The online version contains supplementary material available at 10.1007/s40261-021-01094-7.

Objectives The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided- a critical gap which the current update aims to address. Method Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion. Results No agents met threshold for first line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first line, and lithium and olanzapine identified as second line options. Conclusion The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.

Background It has been hypothesized that polypharmacy may increase the frequency of multidrug interactions (MDIs) where one drug interacts with two or more other drugs, amplifying the risk of associated adverse drug events (ADEs). The main objective of this study was to determine the prevalence of MDIs in medication lists of elderly ambulatory patients and to identify the medications most commonly involved in MDIs that amplify the risk of ADEs. Methods Medication lists stored in the electronic health record (EHR) of 6,545 outpatients ≥60 years old were extracted from the enterprise data warehouse. Network analysis identified patients with three or more interacting medications from their medication lists. Potentially harmful interactions were identified from the enterprise drug-drug interaction alerting system. MDIs were considered to amplify the risk if interactions could increase the probability of ADEs. Results MDIs were identified in 1.3 % of the medication lists, the majority of which involved three interacting drugs (75.6 %) while the remainder involved four (15.6 %) or five or more (8.9 %) interacting drugs. The average number of medications on the lists was 3.1 ± 2.3 in patients with no drug interactions and 8.6 ± 3.4 in patients with MDIs. The prevalence of MDIs on medication lists was greater than 10 % in patients prescribed bupropion, tramadol, trazodone, cyclobenzaprine, fluoxetine, ondansetron, or quetiapine and greater than 20 % in patients prescribed amiodarone or methotrexate. All MDIs were potentially risk-amplifying due to pharmacodynamic interactions, where three or more medications were associated with the same ADE, or pharmacokinetic, where two or more drugs reduced the metabolism of a third drug. The most common drugs involved in MDIs were psychotropic, comprising 35.1 % of all drugs involved. The most common serious potential ADEs associated with the interactions were serotonin syndrome, seizures, prolonged QT interval and bleeding. Conclusions An identifiable number of medications, the majority of which are psychotropic, may be involved in MDIs in elderly ambulatory patients which may amplify the risk of serious ADEs. To mitigate the risk, providers will need to pay special attention to the overlapping drug-drug interactions which result in MDIs.

Purpose/background The aim of this study was to examine the association between genetically predicted CYP2D6 phenotypes and extrapyramidal symptoms (EPSs). Methods/procedures Data from the Tolerability and Efficacy of Antipsychotics trial of adolescents with first-episode psychosis randomized to aripiprazole versus quetiapine extended release were studied. Extrapyramidal symptom assessments included the Simpson-Angus Scale and the Barnes Akathisia Rating Scale. Patients were CYP2D6 genotyped. Plasma concentrations of antipsychotics and antidepressants were analyzed. Findings/results One hundred thirteen youths (age, 12-17 years; males, 30%; antipsychotic naive, 51%) were enrolled. Poor metabolizers had a significantly higher dose-adjusted aripiprazole plasma concentration (±SD) compared with normal metabolizers at week 4 (24.30 ± 6.40 ng/mL per milligram vs 14.85 ± 6.15 ng/mL per milligram; P = 0.019), but not at week 12 (22.15 ± 11.04 ng/mL per milligram vs 14.32 ± 4.52 ng/mL per milligram; P = 0.067). This association was not found in the quetiapine extended release group. No association between CYP2D6 genotype groups and global Barnes Akathisia Rating Scale score or Simpson-Angus Scale score was found in any of the treatment arms. Implications/conclusions Our results do not support routine use of CYP2D6 testing as a predictor of drug-induced parkinsonism or akathisia risk in clinical settings. Further studies with larger samples of CYP2D6 poor metabolizers are needed.

Kwetiapina jest pochodną benzotiazepiny zaliczaną do atypowych leków neuroleptycznych, która w chorobie Parkinsona znajduje zastosowanie w przypadku współistniejących objawów psychotycznych. Chociaż lek jest dobrze tolerowany jego zastosowanie zwłaszcza u pacjentów w podeszłym wieku może wiązać się z różnymi działaniami niepożądanymi. Celem pracy było ustalenie związku pomiędzy wystąpieniem afazji czuciowo – ruchowej u chorego z chorobą Parkinsona i współistniejącymi zaburzeniami psychotycznymi a stosowaniem kwetiapiny. Przedstawiamy przypadek 64 – letniego chorego z rozpoznaną chorobą Parkinsona i współistniejącymi zaburzeniami zachowania w czasie snu REM (RBD) potwierdzonymi w badaniu polisomnograficznym, u którego zastosowanie w terapii dodanej z powodu zaburzeń psychotycznych kwetiapiny (w dawce 50 mg/ dobę) spowodowało wystąpienie zaburzeń mowy o typie afazji mieszanej czuciowo- ruchowej. Afazja wystąpiła w czwartej dobie od rozpoczęcia leczenia atypowym neuroleptykiem. W badaniu MRI głowy nie stwierdzono ,,świeżego'' niedokrwienia mózgowia. W badaniu video- eeg nie zarejestrowano ogniskowego stanu padaczkowego. Całkowite wyleczenie nastąpiło po odstawieniu kwetiapiny. W związku z powyższym jako przyczynę ogniskowych zaburzeń neurologicznych przyjęto efekt uboczny leczenia kwetiapiną.

BACKGROUND Parkinson's disease-related psychosis increases patients' risk of falls. Pimavanserin is an atypical antipsychotic approved in the USA in 2016 for the treatment of hallucinations and delusions associated with Parkinson's disease-related psychosis. OBJECTIVE We aimed to compare the risk of falls/fractures among patients with Parkinson's disease-related psychosis treated with pimavanserin vs other atypical antipsychotics. PATIENTS AND METHODS We identified a cohort of patients with Parkinson's disease-related psychosis aged ≥ 40 years initiating either pimavanserin or a comparator antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) in US commercial insurance and supplementary Medicare claims (2015-2019). Comparators were propensity score matched 2:1 with pimavanserin initiators; incidence rates of falls/fractures were compared using incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS We identified 112 eligible pimavanserin initiators and 982 comparators. Pimavanserin initiators were younger and had fewer severe comorbidities, indicators of impairment, and healthcare encounters, though they had higher Parkinson's disease medication use. The crude incidence rates [cases/100 person-years] (95% CI) for composite falls/fractures were 17.8 (7.7-35.0) for pimavanserin and 40.8 (35.0-47.4) for comparators. Matching retained 108 pimavanserin initiators and 216 comparators-all characteristics were well balanced after matching-with a matched IRR (pimavanserin vs comparator) of 0.71 (95% CI 0.27-1.67). Sensitivity analysis IRR estimates were consistently below 1.00, with a sensitivity analysis not requiring a diagnosis of psychosis resulting in an IRR estimate of 0.55 (95% CI 0.34-0.86). CONCLUSIONS The results of this study do not suggest an increase in the risk of falls or fractures associated with pimavanserin compared with other antipsychotics in patients with Parkinson's disease-related psychosis. Sensitivity analyses suggest a decreased risk.

BACKGROUND Deaths from antipsychotic (AP) poisoning have increased in England and Wales despite restriction of the use of thioridazine in 2000. METHODS We analyzed data from the Office for National Statistics drug-related death database, England and Wales, 1993-2019, to investigate fatal AP poisoning. RESULTS There were 2286 deaths (62% male patients). Annual numbers of intentional AP-related fatal poisonings (suicides) were relatively stable (1993, 35; 2019, 44; median, 44; range, 30-60). Intentional overdose deaths involving clozapine (96 male, 25 female) increased from 1 in 1994 to 5 in 2003 and have since remained relatively constant (median, 6; range, 3-10 per annum). Unintentional second-generation AP-related fatal poisonings have increased steadily since 1998, featuring in 828 (74%) of all unintentional, AP-related fatal poisonings in the period studied (2019, 89%). There were 181 unintentional clozapine-related deaths, (107 [59%] alone without other drugs ± alcohol) as compared with 291 quetiapine-related deaths (86 [30%] alone without other drugs ± alcohol) and 314 unintentional olanzapine-related deaths (77 [25%] alone without other drugs ± alcohol). Some 75% of all unintentional clozapine- and olanzapine-related deaths were of male patients (78% and 73%, respectively) as compared with 58% of unintentional quetiapine-related fatal poisonings. Clozapine now features prominently in intentional and in unintentional AP-related fatal poisoning in England and Wales. Deaths of male patients predominate in both categories. There were also 77 and 86 deaths attributed to unintentional poisoning with olanzapine and with quetiapine, respectively, in the absence of other drugs. CONCLUSIONS More effort is needed to prevent unintentional deaths not only from clozapine but also from olanzapine and quetiapine.

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

Randomized controlled trials (RCTs) have been considered as gold standard for establishing the efficacy and safety of investigational new drugs; nonetheless, the generalizability of their findings has been questioned. To address this issue, an increasing number of naturalistic studies and real-world database analyses have been conducted. The question of how much information from these two approaches is congruent or discrepant with each other is of great importance for the clinical practice. To answer this question, we focused on data from the antipsychotic (AP) treatment of schizophrenia. Our aim was two-fold: to conduct a meta-analysis of real-world studies (RWS), and to compare the results of RWS meta-analysis with previously published meta-analyses of RCTs. The principal measure of effectiveness was all-cause treatment discontinuation for both RWS and RCTs (when not available, then drop out for RCTs). We included publications for 8 selected APs (oral formulations of amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and long-acting injectable (LAI) risperidone). We identified 11 RWS and 7 RCT meta-analyses for inclusion. Our results indicated that the RWS yielded statistically conclusive and consistent findings across individual investigations. For the overwhelming majority of the comparisons where both RWS and RCT meta-analyses were available, there was good congruency between the RWS and the RCT results. Our results support that RCTs, despite their limitations, provide evidence which is generalizable to real-world settings. This is an important finding for both regulators and clinicians. RWS can provide guidance for situations where no evidence is available from double-blind clinical trials.

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 Psychiatry Committee of the Asociacion Colombiana de Psiquiatria [Colombian Psychiatric Association] and on the literature review. It was sent by email to the association members. Results 101 clinicians participated. Non-pharmacological preventive measures such as psychoeducation, correction of sensory problems or sleep hygiene are performed by 70% or more. Only about 1 in 10 participants are part of an institutional multi-component prevention programme. The preventive prescription of drugs was less than 20%. Regarding non-pharmacological treatment, more than 75% recommend correction of sensory difficulties, control of stimuli and reorientation. None of the participants indicated that the care at their centres is organised to enhance non-pharmacological treatment. 17.8% do not use medication in the treatment of delirium. Those who use it prefer haloperidol or quetiapine, particularly in hyperactive or mixed motor subtypes. Conclusions The practices of the respondents coincide with those of other experts around the world. In general, non-pharmacological actions are individual initiatives, which demonstrates the need in Colombian health institutions to commit to addressing delirium, in particular when its prevalence and consequences are indicators of quality of care.

Summary Hyponatraemia is the most common electrolyte disturbance in hospitalised patients and is associated with numerous adverse outcomes. Patients with schizophrenia are particularly susceptible to hyponatraemia, in part due to the close association between this condition and primary polydipsia. We report the case of a 57-year-old woman with schizophrenia and primary polydipsia who was receiving inpatient psychiatric care. She became increasingly confused, had multiple episodes of vomiting, and collapsed 1 week after being commenced on quetiapine 300 mg. On examination, she was hypertensive and her Glasgow coma scale was nine. She had a fixed gaze palsy and a rigid, flexed posture. Investigations revealed extreme hyponatraemia with a serum sodium of 97 mmol/L. A CT brain demonstrated diffused cerebral oedema with sulcal and ventricular effacement. A urine sodium and serum osmolality were consistent with SIAD, which was stimulated by the introduction of quetiapine. The antidiuretic effect of vasopressin limited the kidney’s ability to excrete free water in response to the patients' excessive water intake, resulting in extreme, dilutional hyponatraemia. The patient was treated with two 100 mL boluses of hypertonic 3% saline but deteriorated further and required intubation. She had a complicated ICU course but went on to make a full neurological recovery. This is one of the lowest sodium levels attributed to primary polydipsia or second-generation antipsychotics reported in the literature. Learning points The combination of primary polydipsia and SIAD can lead to a life-threatening, extreme hyponatraemia. SIAD is an uncommon side effect of second-generation anti-psychotics. Serum sodium should be monitored in patients with primary polydipsia when commencing or adjusting psychotropic medications. Symptomatic hyponatraemia is a medical emergency that requires treatment with boluses of hypertonic 3% saline. A serum sodium of less than 105 mmol/L is associated with an increased risk of osmotic demyelination syndrome, therefore the correction should not exceed 8 mmol/L over 24 h.

Background: Clonidine and quetiapine are frequently used medications in the cardiac surgery intensive care unit (ICU). Objective: The purpose of this study is to assess the impact of clonidine compared to quetiapine on cardiac safety outcomes in adult cardiac surgery ICU patients. Methods: This was a single-center, retrospective observational analysis at a tertiary care, academic medical center. Results: One hundred and sixty-one cardiac surgery patients who were administered clonidine or quetiapine during their ICU stay were included between June 2015 and May 2017. The major endpoint of this study was a cardiac safety composite of bradycardia, hypotension, and QTc prolongation. Minor endpoints included ICU and hospital length of stay, and in-hospital mortality. There were 115 patients included in the clonidine arm and 46 patients in the quetiapine arm. There was no difference between groups with regard to the major endpoint (30.43% vs 33.15%; P < .8). There was a shorter ICU and hospital length of stay in the clonidine arm compared to quetiapine P < .0001. All other endpoints were not statistically significant. Conclusion: Patients who received clonidine tended to have undergone less complex procedures, be younger, and have a lower APACHE II score than patients who received quetiapine. The incidence of composite cardiac safety outcomes was not different in clonidine compared to quetiapine in cardiac surgery ICU patients.

The Cotard Syndrome, also known as delirium of negation or nihilistic delirium, was described by the French neurologist, Julius Cotard, on June 1880. From that time until the end of the 20th century, in scientific literature, approximately 100 cases were reported that presented symptoms of depression, anxiety, nihilist delusions concerning the body and existence, hypochondriacal and immortality delusions, as well as auditory and visual hallucinations. We present the case of a female patient, 73-years old, from Ayacucho, with a history of sexual assault at the age of 12 and suicidal attempts on 2 occasions, diagnosed with depression at 40 years of age, received treatment with quetiapine, trazadone and clonazepam. She remained with fluctuating medical progress, with symptoms worsening with stressors such as the death of her mother and husband and when she underwent surgeries. Currently, she presents sad and anxious mood, daily crying, ideas of guilt, disability and death, insomnia of conciliation, nihilistic delusive ideas concerning the body, referring that her stomach and bladder do not work, reason why she doesn’t want to eat or drink water. Due to the total refusal of food intake and persistent suicidal ideation, she was hospitalized to receive psychiatric treatment and nutritional support. It is concluded that there are few cases reported on the use of psychotherapy in Cotard's syndrome. Therefore, this case in which psychotherapy was indicated to reduce anxious-affective symptoms, to avoid isolation of the person and to redirect his personal and social life, is important. El Síndrome de Cotard también conocido como delirio de negación o nihilista, fue descrito por el neurólogo francés Julius Cotard en junio de 1880. Desde esa época hasta fines del siglo XX se ha reportado en la literatura científica aproximadamente 100 casos. Que presentaban sintomatología depresiva, ansiosa, delusiones nihilistas concernientes al cuerpo y a la existencia, delusiones hipocondriacas y de inmortalidad, así como alucinaciones auditivas y visuales. Se presenta el caso de una mujer de 73 años, natural de Ayacucho, con antecedentes de agresión sexual a los 12 años, y episodios de intento de suicidio en dos oportunidades, siendo diagnosticada de depresión a los 40 años, recibió tratamiento con quetiapina, trazadona y clonazepam. Se mantuvo con evolución fluctuante, empeoraron sus síntomas con factores estresantes como el fallecimiento de su mamá, esposo y cirugías a las que fue sometida. Actualmente presenta ánimo triste y ansioso, llanto diario, ideas de culpa, minusvalía y tanáticas, insomnio de conciliación, delusiones nihilistas concernientes al cuerpo, refiriendo que su estómago y vejiga no funciona, por tal motivo no desea comer ni ingerir agua. Debido al rechazo total a ingesta de alimentos e ideación suicida persistente fue hospitalizada para recibir tratamiento psiquiátrico y soporte nutricional. Se concluye que, existen pocos casos reportados sobre el uso de la psicoterapia en el síndrome de Cotard. Por lo tanto, el presente caso en el que se indicó la psicoterapia para reducir síntomas ansioso – afectivos, para evitar el aislamiento de la persona y para reconducir su vida personal y social, es de importancia.

Background Restless arms syndrome (RAS) is characterized by uncomfortable aching or burning sensations in the arms. RAS is regarded as an upper limb variant of restless legs syndrome (RLS). The lack of specific diagnostic criteria makes it difficult to recognize the RAS. Therefore, RAS is usually neglected in clinical practice. Moreover, when a patient was diagnosed with RAS, the adjustment of medications was the first choice for doctors, which may make the patient’s condition unstable. Case presentation A 33-year-old woman was diagnosed with schizophrenia and major depressive disorder. Starting with 0.6 g/d amisulpride, 0.1 g/d quetiapine, 75 mg/d venlafaxine sustained-release tablets, the patient reported symptoms of RAS (itching arms) on the fourth day since the latest hospitalization. After ruling out other factors, her RAS was suspected to be induced by antidepressants or antipsychotics. Without medication adjustment, RAS spontaneously remitted. Conclusions This case suggests that psychiatrists should pay attention to RAS when using antipsychotics and/or antidepressants. Moreover, RAS may be transitory. When a patient manifests RAS, observation may be one choice instead of an immediate medication adjustment.

Determining the optimal antipsychotic target dose in acute phase treatment is of high clinical relevance. The effect of antipsychotics on negative symptoms should be taken into account because patients will often continue on the treatment received in the acute phase. Therefore, we conducted a formal dose-response meta-analysis of negative symptoms and positive symptoms based on a systematic review of fixed-dose randomized controlled trials (RCTs) that examined the effectiveness of antipsychotics for the acute exacerbation of schizophrenia. Forty RCTs included a total of 15,689 patients. The 95% effective doses per day for the 13 antipsychotics included and 3 long acting were mostly different for negative and positive symptoms: amisulpride (481 mg, 690.6 mg); aripiprazole (11.9 mg, 11 mg); asenapine (7.61 mg, 5.66 mg); brexpiprazole (2.1 mg, 4 mg); cariprazine (4 mg, 6.51 mg); haloperidol (6.34 mg, 7.36 mg); lurasidone (58.2 mg, 86.3 mg); olanzapine (15.5 mg, 9.52 mg); olanzapine long-acting injection (15.7 mg, 13.5 mg); paliperidone (7.2 mg, 7 mg); paliperidone long-acting injection (7.5 mg, 5.9 mg); quetiapine instant-release (264.2 mg, 316.5 mg); quetiapine extended-release (774 mg, 707.2 mg); risperidone (7.5 mg, 7.7 mg); risperidone long-acting injection (5.13 mg, 6.7 mg); sertindole (13.5 mg, 16.3 mg); and ziprasidone (71.6 mg, 152.6 mg). The shape of the dose-response curves varied across different drugs with most drugs showing a plateau at higher doses. Most dose-response curves suggested that the near-maximum effective doses could be in the lower-to-medium range of the licensed dose. Additional RCTs are necessary to establish the optimal dose.

Life time psychiatric comorbidities of bipolar disorders are highly prevalent. Anxiety disorders, alcohol-substance use disorders, obsessive-compulsive disorder and attention deficit and hyperactivity disorder are the most common comorbid psychiatric conditions in bipolar disorders. Psychiatric comorbidity of bipolar disorders is strongly associated with poor treatment response, higher recurrence of mood episodes, suicide attempts, rapid-cycling, worse general functioning and quality of life. Therefore, considering the huge impact of comorbidity on the bipolar disorder illness course, treatment is usually challenging. The primary aim of the treatment in psychiatric comorbidity of bipolar disorder should be mood stabilization and prevention of mood episodes. Then, first line treatment options recommended for the specific psychiatric disorders might be preferred for the treatment of bipolar disorder comorbidity. With this rationale, quetiapine can be listed as a first line treatment for anxiety disorders comorbidity in bipolar disorders while serotonergic antidepressants and olanzapine are recommended as second line options. For the treatment of alcohol-substance use disorders comorbidity, first line mood stabilizers such as valproate and lithium and new generation antipsychotic quetiapine seem to be the leading options. Serotonergic antidepressants for obsessive-compulsive disorder and stimulants for the attention-deficit hyperactivity disorders are the key treatment choices. However, both treatment agents might cause to manic switch and mood destabilization. Thus, clinicians should be aware of these complications when prescribing in bipolar disorders comorbidity.

Neuroleptic malignant syndrome caused by atypical antipsychotic drugs may present in an atypical manner without symptoms such as hyperthermia and/or muscle rigidity. A detailed description of atypical neuroleptic malignant syndrome induced by atypical antipsychotic drugs, practical information to distinguish neuroleptic malignant syndrome from other related conditions, and the diagnostic criteria that may be used to settle the diagnosis of atypical neuroleptic malignant syndrome are highlighted in this paper. This study was conducted searching PubMed and Science Direct, resulting in 525 articles. 26 case reports that met inclusion criteria were identified. Atypical neuroleptic malignant syndrome was found to develop mainly in male patients suffering from schizophrenia (14 cases) and bipolar disorder (2), and was induced by clozapine (6 cases), olanzapine (5 cases), aripiprazole and quetiapine (4 cases). Muscle rigidity did not develop in patients treated with clozapine and quetiapine, whereas a lack of hyperthermia was common with aripiprazole and clozapine treatment. Atypical neuroleptic malignant syndrome is a difficult matter, especially when symptoms of hyperthermia or muscle rigidity is lacking, but using Levenson's or Adityanjee and Aderibigbe's criteria may increase it detectability, can permit earlier intervention and prevent development of life-threatening typical neuroleptic malignant syndrome.

The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10-5 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.

Objective:Abuse of psychoactive drugs for therapeutic purposes is becoming more common due to their addiction potential. In many studies, quetiapine has been reported to be abused with illicit drugs. We aimed to point to the abuse and addiction potential of quetiapine by the rates of quetiapine abuse in blood samples of 4,293 cases who came to our Forensic Toxicology Laboratory by using liquid chromatography-tandem mass spectrometry method.Methods:All cases who were caught by law enforcement officers while using or trading drugs as a requirement of the judicial process initiated were drug users or dealers and then they were brought to our forensic toxicology laboratory to obtain blood and urine samples. Quantification in blood samples was performed in routine laboratory analysis. The cases were asked whether they used any prescription drugs. The therapeutic drug users were excluded in this study.Results:Quetiapine was positive in 50 of 4,293 cases (1.16%). 93.8% (n=4028) of all cases and all of the positive quetiapine were male. While quetiapine was used alone in 11 of 50 cases with quetiapine positivity, quetiapine was used simultaneously with one or more groups of illicit drugs in the remaining 39 cases.Conclusion:In this study, the most common use of cannabis and quetiapine was determined in cases with drugs of abuse. The monitoring of quetiapine is essential for preventing drug abuse especially in prone population such as illicit drug abusers and addicts. Forensic Toxicology Laboratories play an important role in taking necessary preventions related to drug abuse.

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo/manic episodes (termed predominant hypo/manic polarity). We examined the associations between staging and predominant polarity with measures of illness burden and treatment outcome utilizing data from a six-month comparative effectiveness trial of lithium and quetiapine in bipolar disorder (Bipolar CHOICE). We used number of self-reported lifetime mood (depressive and hypo/manic) episodes as a proxy for staging and ratio of depressive to manic episodes to define predominant polarity. Polarity and staging were correlated with several measures of burden of illness. Childhood abuse was correlated with more lifetime mood episodes, while more depressive episodes and depressive polarity were correlated with more anxiety disorder comorbidity. Depressive polarity was also correlated with more past trials of psychotropics, particularly antidepressants. However, neither staging nor predominant polarity moderated the randomized treatment effect of lithium vs. quetiapine. Number of depressive episodes in the past year was identified as a potential predictor of overall worse treatment outcome, regardless of medication condition. In conclusion, though staging and predominant episode polarity correlated with several measures of illness burden, they were not associated with differential treatment outcomes. This could be because many of our patients presented for treatment at advanced stages of illness and further highlights the need for early intervention in bipolar disorder.

Dengue is an arboviral infection endemic in tropical countries. Neurological sequelae to dengue infection are not uncommon, and psychiatric manifestations are increasingly reported. This narrative review aims to present the varied manifestations, postulated mechanisms, and the available treatment options for psychiatric morbidity associated with dengue. The evidence available from eight observational studies is summarized in this review. Depression and anxiety are noted to be prevalent during both the acute and convalescent stages of the infection. The presence of encephalopathy and other neurological conditions is not a prerequisite for developing psychiatric disorders. However, treatment options to manage such psychiatric manifestations were not specified in the observational studies. Anecdotal evidence from case reports is outlined. Special attention is paid to the role of epigenetic modifications following dengue infections and the role of histone deacetylase inhibitors in the management. DNA methylation inhibitors such as valproic acid play a significant role in reversing stress-, viral-, or drug-induced epigenetic modifications.

While antipsychotic medications have long been associated with anticholinergic effects, asenapine has been purported to have no capacity for muscarinic cholinergic antagonism based on in vitro studies. Research in rat brain tissue has yielded different results, with one study finding more cholinergic M1-5 binding in the medial prefrontal cortex, dorsolateral frontal cortex and hippocampal CA1 and CA3 areas than would be predicted from in vitro findings. Moreover, it is structurally similar to other anticholinergic antipsychotics such as loxapine and, to a lesser degree, quetiapine, olanzapine and clozapine. This case report describes the anticholinergic toxidrome in a patient treated with benztropine and paroxetine at stable doses, with the emergence of the toxidrome after upward titration of asenapine. A broad differential was considered. With further consideration of the history, time-course, clinical features and physical examination, the presentation is most indicative of the anticholinergic toxidrome. Although not employed, physostigmine, the antidote for anticholinergic delirium, could help to differentiate this toxidrome and serve as a diagnostic and therapeutic intervention. We have presented this case to highlight the importance for clinicians to integrate history and bedside examination data with principles of pharmacology. In particular, asenapine should be added to the list of compounds with recognized anticholinergic potential.

Jan Anker Jahnsen,1– 3 Sofia Frost Widnes,1,2 Jan Schjøtt1– 3 1Regional Medicines Information and Pharmacovigilance Centre (RELIS Vest), Haukeland University Hospital, Bergen, Norway; 2Department of Clinical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway; 3Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, NorwayCorrespondence: Jan Anker JahnsenRegional Medicines Information and Pharmacovigilance Centre (RELIS Vest), Haukeland University Hospital, Bergen, NorwayTel +47-48182071Email jan.anker.jahnsen@helse-bergen.noPurpose: The second-generation antipsychotic quetiapine has been associated with misuse and dependency. We aimed to review questions to the Norwegian network of drug information centers concerning this potential drug safety problem.Methods: We conducted a Boolean search in the database of the Regional Medicines Information and Pharmacovigilance Centres in Norway (RELIS) combining the indexed categories “quetiapine” and “adverse drug reaction” with the text words “misuse” or “dependency”. Question–answer pairs (Q/As) in the full-text, searchable RELIS database were defined as cases. Cases were analyzed for drug safety issues linked to use of quetiapine, including off-label use, polypharmacy and other patient risk factors.Results: The search resulted in 54 cases. Forty-six cases (85%) were patient-related, and a majority came from physicians working in hospitals. Twenty-nine cases (54%) concerned patients with a history of addiction, 14 cases (26%) had polypharmacy, and off-label use of quetiapine for insomnia was identified in 14 of the cases (26%). Only three of the cases included a specific question about patient dependency of quetiapine, and these cases were all associated with insomnia.Conclusion: We conclude that our case series from the Norwegian network of drug information centres reflects that quetiapine frequently involves clinical narratives of a history of addiction, polypharmacy or insomnia (off-label use). However, the case series did not reveal new information about the drug’s addictive potential.Keywords: off-label, insomnia, drug safety, addiction, abuse

Ilena Pochiero,1 Fabrizio Calisti,1 Alessandro Comandini,1 Alessandra Del Vecchio,1 Isabella Costamagna,1 Maria Teresa Rosignoli,1 Agnese Cattaneo,1 Sasikiran Nunna,2 Ilaria Peduto,3 Franca Heiman,3 Hsiu-Ching Chang,2 Chi-Chang Chen,2 Christoph Correll4– 6 1Angelini Regulatory, Research & Development, Angelini Pharma S.p.A., Rome, Italy; 2IQVIA, Plymouth Meeting, PA, USA; 3IQVIA Solutions Italy S.r.l., RWS, Milan, Italy; 4Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; 5Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; 6Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USACorrespondence: Ilena PochieroAngelini Pharma S.p.A., Viale Amelia 70, Rome, ItalyEmail ilena.pochiero@angelinipharma.comPurpose: The primary objectives were to describe weight changes following initiation of lurasidone versus other antipsychotics and estimate the risk of clinically relevant (≥ 7%) weight changes.Patients and Methods: This retrospective, longitudinal comparative cohort study was based on electronic medical records (EMRs) of United States (US) adult patients with schizophrenia who were prescribed lurasidone or other antipsychotics as monotherapy between 1 April 2013 and 30 June 2019.Results: Overall, the study included 15,323 patients with a diagnosis of schizophrenia; 6.1% of patients received lurasidone, 60.4% received antipsychotics associated with a medium-high risk of weight gain (clozapine, olanzapine, quetiapine, risperidone, paliperidone) and 33.5% received antipsychotics with a low risk of weight gain (aripiprazole, first-generation antipsychotics, ziprasidone). Lurasidone was associated with the smallest proportion of patients experiencing clinically relevant weight gain and the greatest proportion of patients with clinically relevant weight loss. The risk of clinically relevant weight gain was numerically higher with all antipsychotics versus lurasidone and was statistically significant for olanzapine (hazard ratio [HR]=1.541; 95% confidence interval [CI]=1.121; 2.119; p=0.0078) versus lurasidone. The likelihood of ≥ 7% weight loss was significantly greater with lurasidone versus all antipsychotics (p< 0.05), except ziprasidone.Conclusion: This real-world study suggests that lurasidone has a lower risk of clinically relevant weight gain and a higher likelihood of clinically relevant weight loss than other commonly used antipsychotics.Keywords: retrospective studies, weight gain, real world clinical trials

Purpose/background Bipolar disorder and major depressive disorder are heterogeneous conditions characterized by marked variations in mood. High levels of anxiety are often present in these conditions and are associated with increased suicidal risk, increased disease duration, and treatment resistance. Mood stabilizers or antipsychotics are recommended for the treatment of bipolar disorder in comorbidity with anxiety disorders. This study examines current knowledge to evaluate the efficacy of quetiapine in the treatment of anxiety in mood disorders. Methods/procedures A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials that evaluated the efficacy of quetiapine on anxiety symptoms in patients diagnosed with bipolar disorder or major depressive disorder and included anxiety evaluation scales. Findings/results We collected 27 studies (19 with primary data analysis, 8 with secondary data analysis) regarding the use of quetiapine in mood disorders. Quetiapine was more effective than placebo and active comparators in reducing anxiety in unipolar and bipolar patients in 20 of these studies. In 7 studies, quetiapine was not superior to psychoactive comparators or placebo on the anxiety dimension. Implications/conclusions Statistical power might be limited by small sample size in 5 of the studies included in our review. Moreover, data on anxiety were a secondary outcome in most studies. Nevertheless, the reported studies show with good levels of concordance that quetiapine is effective in controlling anxiety symptoms in patients with mood disorders. This evidence supports current guidelines and recommendations concerning the use of quetiapine in clinical practice.

Quetiapine is an antipsychotic drug with proven efficacy in the treatment of schizophrenia and bipolar disorder as well as recurrent depression and generalized anxiety disorder. There is also evidence of the efficacy of quetiapine in other disorders dominated by affective and/or anxiety symptoms, for which treatment is not registered in Poland. The paper presents information useful in medical practice and presents descriptions of use cases.

Background The use of atypical antipsychotics for the treatment of schizophrenia and other mental disorders in populations under 18 years of age is increasing worldwide. Little is known about treatment patterns and the influence of gender differences, which may be a predictor of clinical outcomes. The aim of this study was to investigate gender differences in the use of atypical antipsychotics in patients with early-onset schizophrenia (EOS) assisted by the public health system in Brazil. Methods We conducted a cross-sectional study of outpatients with EOS aged 10 to 17 years who received at least one provision of atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a large Brazilian pharmaceutical assistance programme. Data were retrieved from a nationwide administrative database from 2008 to 2017. Results Of the 49,943 patients with EOS, 63.5% were males, and the mean age was 13.6 years old. The patients were using risperidone (62.5%), olanzapine (19.6%), quetiapine (12.4%), ziprasidone (3.3%) and clozapine (2.2%). We found gender differences, especially in the 13–17 year age group (65.1% for males vs. 34.9% for females, p p p p = 0.012) and quetiapine (p = 0.041) slightly higher for males than for females. Conclusions Our findings showed gender differences among patients diagnosed with EOS and who received atypical antipsychotics. More attention should be devoted to gender differences in research and clinical practice.

Khalid Orayj Clinical Pharmacy Department, School of Pharmacy, King Khalid University, Abha, Saudi ArabiaCorrespondence: Khalid OrayjClinical Pharmacy Department, School of Pharmacy, King Khalid University, P.O. Box: 960, Abha, 62529, Saudi ArabiaTel +966505442013Email Korayg@kku.edu.saPurpose: Psychosis is very common in later stages of Parkinson’s disease (PD) patients, but its prevalence in newly diagnosed patients is not rare. The use of antipsychotics in PD patients is complex given their association with worsening Parkinsonian motor symptoms and increased mortality rate. This study aims to examine factors that affect the use of antipsychotics in newly diagnosed PD patients and to identify changes in prescribing over time.Patients and Methods: The Secure Anonymized Information Linkage (SAIL) databank was used to identify a cohort of newly diagnosed PD patients aged 40 years and older in Wales. The cohort was longitudinally examined over 17 years to determine the incidence of new antipsychotic use. Logistic regression models were used to analyze the data and were adjusted for several potential confounding variables.Results: A total of 9142 PD patients were identified after applying inclusion and exclusion criteria, of whom 58.6% were male. During the first year of PD diagnosis, 12% of the patients developed psychosis and were prescribed antipsychotics. Quetiapine was the most commonly prescribed (49%), followed by risperidone (10.7%). The use of antipsychotics in newly diagnosed PD patients was significantly lower in the years 2009– 2016 compared to 2000– 2008 (OR 0.37, 95% CI 0.32– 0.43). Other significant prescribing factors included patient’s age and history of dementia.Conclusion: A dramatic decline in antipsychotic use was identified across years, showing adherence to warnings against use of antipsychotics for PD patients. Given that psychosis is prevalent in PD patients, the continuous assessment of the safety risks of antipsychotics is a matter of priority.Keywords: Parkinson’s disease, psychosis, pattern of prescribing, mortality risk

Objective In a number of controlled clinical trials and naturalistic studies, aripiprazole once monthly (AOM) has been found to be effective and safe as acute and maintenance treatment options for schizophrenia. However, such clinical data have been presented in selected patient population (i.e., antipsychotic monotherapy, etc.), in particular, clinical information on switching to AOM from antipsychotic polypharmacy and/or other long acting injectable antipsychotics (LAIs) has been scarce till today. Methods The study period was from the first switching day to AOM up to 12 months in patients with antipsychotic polypharmacy (APpoly)/LAIs (baseline, month 3, month 6, and month 12). Available demographics and clinical information were retrieved from electronic medical records (EMRs). Available scores of Global Assessment of Functioning (GAF), Clinical Global Impression-Clinical Benefit (CGI-CB), CGI-severity, Visual Analog Scale on Satisfaction-Patient/Health Professional (VAS-P/HP), and the Positive and Negative Syndrome Scale-Insigh (PANSS-I) scores were also taken from EMR. Proportional change of functional impairment before and after AOM was also captured. Results Data of 18 patients were available. Most commonly used combined APs before AOM were aripiprazole, blonanserin, quetiapine, and risperidone. At least 2 APs (n = 2.4) were combined before AOM. Scores of GAF (10.7% increase), CGI-CB (46.2% decrease), VAS-P (47.8% increase), VAS-HP (40.8% increase), and PANSS-I (27.9% increase) (all p = 0.001) were significantly improved from baseline to month 12, respectively. Approximately 59% of patients improved individual functioning with different level (i.e., employment, back to school, etc.) after AOM treatment at month 12. Conclusion The present study have clearly shown the clinical benefit and utility of switching to AOM for treatment of patients with APpoly/LAIs in routine practice. Subsequent, adequately-powered, well-controlled clinical trials may be necessary to confirm our findings in near future.

(1) Introduction: Quetiapine (QTP) is a dibenzothiazepine derivative, a second generation antipsychotic (AP), which is structurally similar to clozapine. The main indications for use are schizophrenia and depressive disorder. Under manic episodes in bipolar disorder can be used alone or in combination with lithium. The frequency of prescribing QTP is on average 11,987 per 100,000 population, with a positive trend in dynamics: a growth rate of more than 800% within the period 2002 to 2017.(2) Purpose: The review of studies of pharmacogenetic pharmacokinetic and pharmacogenetic pharmacodynamic markers of QTP efficacy and safety.(3) Materials and Methods: A search was carried out for publications of the Science Index, PubMed, Web of Science, Springer databases by keywords and their combinations over the last 10 years. In addition, the review includes earlier publications of historical interest. Despite extensive searches of these commonly used databases and search terms, it cannot be ruled out that some publications may have been missed.(4) Results: The review considers the following pharmacokinetic markers of QTP efficacy and safety: genes are coding isoforms of cytochrome P450 (CYP2D6, CYP2C19, CYP3A4, CYP3A5), P-glycoprotein (ABCB1); pharmacogenetic pharmacodynamic markers of the efficacy and safety of QTP : genes of dopamine receptor isoform (DRD3), dopamine transporter (SCL1A1) and catecholO-methyltransferase (COMT), serotonin receptor isoforms (HTR2C), melanocortin receptor (MC4R), NOTCH protein (NOTCH4), phosphodiesterase 4D (PDE4D), SPoPL protein (SPoPL), multiple EGFlike domain (MEGF10), protocadherin-7 (PCDH7), contactin-associated protein 5 (CNTNAP5) , TRAF2 and NCK-interacting protein kinase (TNIK), spermatogenesis-associated protein 6 (SPATA6L), neurobihin (NBEA), synaptic vesicle protein-2C (SVC2) .(5) Conclusion: Disclosure of pharmacogenetic markers of pharmacokinetics and pharmacodynamics of QTP efficacy and safety in the treatment of patients with schizophrenia and other psychiatric disorders, may provide a key to developing a strategy for its personalized prevention of adverse grug reactions (ADRs) and therapy strategy in real clinical practice.

This case report describes a unique presentation of Cotard syndrome in an 18-year-old female patient experiencing first-episode psychosis. Cotard syndrome was first described in 1880 by Jules Cotard as a novel subtype of anxious depression and is presently understood as a rare cluster of mood and psychotic symptoms centered on nihilistic delusions including the absence of organs and a perception of being dead. Although rare, Cotard syndrome has been described in a variety of neurological and psychiatric illnesses, but it is most commonly seen in middle-aged adults with a history of chronic mood disorders. It is rarely reported in childhood or adolescence, and it has not previously been described in first-episode psychosis. This report describes a unique presentation of full Cotard syndrome in an adolescent patient experiencing first-episode psychosis without reported mood symptoms. The patient displayed limited improvement over the first week of treatment with quetiapine but improved rapidly during the second week of hospitalization after a medication change to risperidone. The patient's rapid response to risperidone is unique, as most existing evidence suggests that electroconvulsive therapy is the most effective treatment for Cotard syndrome. This response indicates an opportunity for the implementation of a second-generation antipsychotic medication in patients with Cotard syndrome in areas where electroconvulsive therapy is not available.

The second-generation antipsychotic drug quetiapine (Seroquel) is increasingly being used off-label for treating insomnia in the general population, possibly to avoid standard medications with known addictive qualities and adverse side effects. However, evidence to support using it in this way is scant, and quetiapine is associated with weight gain and other metabolic effects. It must be used cautiously and with appropriate monitoring for adverse effects and abuse.

The lack of female participation in antipsychotic trials for schizophrenia poses an important issue regarding its applicability, with direct and real-life repercussions to clinical practice. Here, our aim is to systematically review the sampling sex bias among randomized clinical trials (RCTs) of second-generation antipsychotics—namely risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole—as an update to a previous 2005 review. We searched MEDLINE and the Cochrane database for studies published through 7 September 2020 that assessed adult samples of at least 50 subjects with a diagnosis of schizophrenia, schizophrenia spectrum disorder, or broad psychosis, in order to investigate the percentage of women recruited and associated factors. Our review included 148 RCTs, published from 1993 to 2020, encompassing 43,961 subjects. Overall, the mean proportion of women was 34%, but only 17 trials included 50% or more females. Younger samples, studies conducted in North America, pharmaceutical funding and presence of specific exclusion criteria for women (i.e., pregnancy, breast-feeding or lack of reliable contraceptive) were associated with a lower prevalence of women in the trials. Considering the possible different effects of antipsychotics in both sexes, and our lack of knowledge on the subject due to sampling bias, it is imperative to expand actions aimed at bridging this gap.

Background While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT’s) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression. Methods Efficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement – Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated. Results Eighteen RCT’s met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (− 4.71 [95% Crl − 6.98, − 2.41]), quetiapine (− 4.80 [− 5.93, − 3.72]), olanzapine (− 4.57 [− 5.92, − 3.20]), and cariprazine (− 2.29 [− 3.47, − 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (− 0.38 [95% Crl − 0.66,-0.10]) and ziprasidone (− 0.58 [− 0.91,-0.26]), but similar to quetiapine (− 0.08 [− 0.36, 0.19])and olanzapine (− 0.04 [− 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl − 0.22, 0.89]) and aripiprazole (0.20 kg [− 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12). Conclusions In this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.

WstępW literaturze można znaleźć opisy przypadków wskazujące na fałszywie dodatnie wyniki powszechnie wykonywanych testów na obecność substancji psychoaktywnych u osób przyjmujących zalecone przez lekarza leki psychotropowe. Wiarygodność przeprowadzanych testów ma ogromne znaczenie dla badanej osoby, biorąc pod uwagę zarówno aspekty kliniczne, jak i możliwe skutki prawne. Celem pracy był przegląd literatury dotyczącej fałszywie dodatnich wyników testów narkotykowych u pacjentów przyjmujących leki psychotropowe.Materiał i metodyDokonano przeglądu narracyjnego dostępnej literatury w języku angielskim i polskim korzystając z baz MEDLINE/PubMed oraz Google Scholar, używając słów kluczy: fałszywie dodatni wynik testu narkotykowego oraz nazw zarejestrowanych leków z grup: przeciwdepresyjnych, przeciwpsychotycznych, stabilizujących nastrój, a także używanych w leczeniu zespołu hiperkinetycznego. Wzięto pod uwagę artykułu typu przeglądowego, opisy przypadków oraz prace oryginalne z lat 1990-2019.WynikiFałszywie dodatnie wyniki testów narkotykowych odnotowano w przypadku wielu leków używanych w psychiatrii: klomipraminy, amitryptyliny, bupropionu, trazodonu, sertraliny, wenlafaksyny, hydroksyzyny, haloperidolu, sulpirydu, pernazyny, lewomepromazyny, arypiprazolu, rysperydonu, amisulprydu, kwetiapiny, lamotryginy, karbamazepiny, metylofenidatu i atomoksetyny. Dla pozostałych leków branych pod uwagę w pracy nie znaleziono takich doniesień.WnioskiPrzy interpretacji testów narkotykowych z moczu należy zachować ostrożność, szczególnie gdy badana osoba wyraźnie zaprzecza zażywaniu substancji psychoaktywnych. W takich sytuacjach należy dokładnie przeanalizować stosowane leki i upewnić się, czy uzyskany wynik nie jest wynikiem fałszywie dodatnim. Skuteczną metodą pozwalającą potwierdzić lub wykluczyć obecność narkotyków w moczu w przypadku niejasnych wyników testów jest chromatografia gazowa. Niestety większość dostępnych w literaturze danych stanowią opisy przypadków, zasadne wydaje się być zatem przeprowadzenie badań na dużej grupie osób przyjmujących leki psychotropowe.

The article presents the results of a randomized comparative study of Aripiprazole and Quetiapine in the treatment of patients with a dual diagnosis: schizophrenia and substance use disorders. During the study, 90 of the 266 male patients were screened. Among them, 54 individuals (60%) had a previously established diagnosis of mental disorder and 36 patients (40%) had no established psychiatric diagnosis. They were randomly randomized into three groups of 30 patients, each receiving an antipsychotic: Aripiprazole at a dose of up to 20 mg daily, Quetiapine at a dose of up to 600 mg daily, or Haloperidol at a dose of up to 30 mg daily. The efficacy of Aripiprazole and Quetiapine was evaluated using the following scales: PANSS, BPRS, VAS, and Substance Craving Scale (SCS). Drug safety was assessed by the development of adverse events, serious adverse events, or adverse reactions. Study results demonstrated the efficacy of atypical antipsychotics in the three groups. Analysis of independent variables showed significant differences between Aripiprazole and Haloperidol in PANSS and BPRS scores by Visit 4, in VAS scores by Visit 3, and in SCS scores by Visit 2. Intergroup analysis of independent variables showed significant differences between Quetiapine and Haloperidol in PANSS, VAS, and SCS scores by Visit 4. Intergroup analysis of independent variables showed significant differences between Aripiprazole and Quetiapine in the VAS and SCS scores. The correlation analysis allowed drawing conclusions about the close connection of the symptoms of schizophrenia and substance use disorders in patients with a dual diagnosis.

Post-stroke depression is a frequent complication of cerebrovascular lesions and mainly occurs within the first 6 months after stroke. Stroke patients who develop depression have slower recovery, greater disability, and higher mortality rates. The pathophysiology of post-stroke depression is not yet clearly defined, but studies suggest contributions from both psychosocial factors and stroke-related factors, such as lesions affecting the frontal-subcortical circuits. Early treatment has a positive impact on post-stroke rehabilitation outcome and survival. We present the case of an 82-year-old man with no psychiatric history who was brought to the psychiatric emergency department after two suicide attempts in the span of 7 days. He was severely depressed, with feelings of hopelessness, insomnia, and suicidal ideation. He had suffered a stroke the week before, affecting the anterior portion of the left cingulate gyrus, causing right hemiparesis and paresthesia. The psychiatric symptoms developed immediately after the stroke and were not present before the event. He was admitted to the psychiatry ward, treated with sertraline 100 mg/day and quetiapine 50 mg/day and discharged within 28 days, after full remission of symptoms. Our case strengthens the association between lesions located to the frontal-subcortical circuits and post-stroke depression. Physicians should be vigilant regarding the occurrence of depression in stroke patients, especially those who suffer lesions affecting the frontal-subcortical circuits and related regions.

LEARNING OBJECTIVE After participating in this activity, learners should be better able to:• Evaluate the evidence regarding the effectiveness of long-term treatment of bipolar disorder with valproate. BACKGROUND Prophylactic treatment is critical for bipolar disorder (BD) patients. Valproate is commonly used for this purpose but lacks regulatory approval and carries appreciable risks. METHODS Systematic literature searching through June 2020 sought prospective trials lasting ≥12 months with adults diagnosed with BD to support comparisons of risk of new illness episodes with valproate versus placebo or other agents. RESULTS Included were 13 reports involving 9240 subjects treated for an average of 29.1 months (range, 12-124) in 21 trials: 9 were blinded, randomized trials (RCTs) of valproate versus placebo (n = 3), lithium (5), or olanzapine (1); 2 were unblinded RCTs versus lithium (1) or quetiapine (1); and 10 were open-label trials versus lithium (5), quetiapine (2), carbamazepine (1), lamotrigine (1), or olanzapine (1). Random-effects meta-analysis found valproate superior to placebo in 3 trials (odds ratio [OR] = 0.42 [95% confidence level (CI), 0.30-0.60]; p < .0001). In 11 trials, protective effects with valproate and lithium were similar (OR = 1.20 [CI, 0.81-1.79]; p = .36), as well in 5 comparisons versus antipsychotics quetiapine and olanzapine (OR = 0.96 [CI, 0.66-1.40]; p = .84), and 2 versus other mood-stabilizing anticonvulsants (carbamazepine and lamotrigine) (OR = 1.30 [CI, 0.75-2.26]; p = .34). Valproate was nonsignificantly more effective versus new mania than depression (χ2 = 3.03; p = .08). CONCLUSIONS Valproate was more effective than placebo in preventing new BD episodes of mania or depression, and not significantly different from lithium, second-generation antipsychotics, or other anticonvulsants. Overall benefits were nonsignificantly greater versus mania than bipolar depression.

Background Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. Methods The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. Results The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). Conclusions The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

The goals of the treatment of dementia is to slow down the progression of neurological changes and reduce the severity of symptoms. One of the early symptoms of the development of neurological diseases is late-onset depression, which is associated with impaired functioning of the prefrontal circuits, prefrontal-striatal dysfunction, which is responsible for cognitive-depressive dysfunction. This syndrome responds poorly to antidepressants and better to dopaminergic drugs. Based on the literature and clinical experience, we can conclude that the combination of donepezil and quetiapine may provide many benefits to patients with dementia and is well tolerated. Cholinesterase inhibitors (i.e. donepezil) have the best proven effect in the first stage of the disease, when cholinergic deficiency is most prevalent, and benefit from 30–50% of patients. Quetiapine has a lower potential for developing weight gain and metabolic complications, and for producing hyperprolactinaemia and extrapyramidal symptoms, and is better tolerated.