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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.

Quetiapine fumarate is an atypical antipsychotic drug, which is clinically used for the treatment of depression and bipolar disorders. A stability indicating method is required for the quality control of pharmaceutical dosage forms. This work focused on the developments of a rapid stability indicating reversed-phase HPLC-UV method for determination of quetiapine fumarate in tablets and extemporaneous formulations. Quetiapine fumarate was simultaneously determined in the presence of three impurities: quetiapine related compound B, quetiapine related compound G, and quetiapine N-oxide within 9 min. Optimal HPLC conditions were realized using Zorbax C8 column (100 mm × 4.6 cm i.d., 3 μm particle). Gradient elution utilized mobile composition of 0.15% triethylamine (pH 6.0) and acetonitrile : methanol (80:20) mixture at a flow rate of 1.2 mL/min with detection wavelength at 252 nm. The proposed method showed good linearity (r2 > 0.998), precision (RSDs ≤ 2.2), and accuracy (%recovery 96.8 – 99.4, RSD ≤ 1.9) with acceptable limits of detection (LOD ≤ 3.0 μg/mL) and quantitation (LOQ ≤ 10 μg/mL) at RSD ≤ 2.8). The method was successfully applied to the determination of quetiapine fumarate in pharmaceutical formulations and stability testing of extemporaneous formulations.

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.