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The continuous monitoring of antipsychotic drug release in the patient undergoing treatment is significant for dose monitoring. Hence, as a part of treatment, frequent blood tests are required to detect the drug level. In this context, the development of a miniaturized POC (Point-of-Care) Electrochemical sensing platform plays a significant role. The present work demonstrates the realization of a paper-based electrochemical sensing device for sensing of antipsychotic drug Clozapine (CLZ). A commercial Toray paper was used as a base electrode that showed high conductivity, mechanical strength, and gas permeability, hence appropriate for electrochemical sensing. Toray fibrous carbon electrodes were used for the sensing of CLZ. The CO 2 laser system with optimized speed (6.5 %) and power (4.5 %) was efficiently used to fabricate a simple, low-cost, and miniaturized Toray paper electrochemical device (TPED). The electrode surface was characterized using scanning electron microscopy, which showed a high porous gas diffusion layer with denser carbon. Cyclic Voltammetry (CV) and Chronoamperometry (CA) techniques were used to study the electrochemical characterization of the CLZ. The analytical performance of TPED was validated by sensing various concentrations of CLZ in a linear range from 0.5 µM to 5 µM with a Limit of detection (LoD) of 0.5 µM and a Limit of Quantification (LoQ) of 1.69 µM using cyclic voltammetry and the linear from 0.5 µM to 5 µM with a limit of detection (LoD) of 0.01 µM and Limit of Quantification (LoQ) of 0.05 µM using chronoamperometry techniques. Furthermore, the interference mitigation of TPED was examined with other biomolecules. Finally, the practicability of TPED was tested by performing a real sample analysis in blood serum. Based on the analytical performance, it was confirmed that the fabricated device has the ability to be applied in biomedical applications for drug sensing in point-of-care testing. [Display omitted] • Novel Miniaturized Toray paper-based device for clozapine detection is presented. • The device was characterized by various electrochemical techniques. • A Linear concentration range of 0.5 µM to 5 µM was achieved. • LOD and LOQ of 0.5 µM and 0.69 µM, respectively were obtained. • Serum sample was used for real sample analysis and upto 98 % efficacy obtained. [ABSTRACT FROM AUTHOR]

• Good documentation practice is the foundation for promoting medication safety in young population. • Study identified poor documentation practice through paper and electronic means of medical records. • Newly introduced electronic medical records did not improve the rates of metabolic monitoring nor the quality of documented monitoring. • Youth are at significant risk for antipsychotic induced metabolic syndrome the repercussion of which may impact years of productivity. • Potentially electronic health records could provide health workers with real-time information access, and develop accurate, relevant and structured information thereby adhering to clinical evidence. Since the development of digital records, claims have been made that they improve audits. Clinical audits play important role in evaluation of evidence-practice gaps. Antipsychotic medications are one of the commonly prescribed group of drugs in severe adverse mental conditions. Youth and young people are highly prone to develop drug induced metabolic syndrome. Present study evaluated the extent of data documentation on evidence for metabolic monitoring of antipsychotics and compared paper based to electronic records with good documentation standards. First phase of this study involved a retrospective clinical audit of paper-based documentation on the extent of documentation of weight (primary outcome); lipid and blood glucose (secondary outcomes) of youth prescribed atypical antipsychotics. This was undertaken in three public mental health clinics and a public/private developmental service in Australia based on paper-based documentation. The second phase included auditing electronic data capture from one community clinic. Evidence of documentation was compared with practice standards and published clinical audits (adherence rate benchmark: 40–60%). A total of 310 cases were assessed of which 51 and 37 cases met the eligibility criteria for paper-based and electronic based audit respectively as a component of clinical audit. Evidence of paper documentation of weight was 43% among participants and was comparable with other published clinical audits (p = 0.07) with poor monitoring rates for other blood tests. Findings revealed poor rate of documentation at 35.1% (13 cases), 5.4% (2 cases) and 8.1% (3 cases) for weight, lipid assessments and glucose monitoring, respectively based on electronic records. Present study demonstrate lack of good documentation practices on metabolic monitoring of youth prescribed antipsychotics. It appears transitioning from paper to electronic records did not impact the rate of increase in documentation of metabolic monitoring. This study recommends inclusion of e-monitoring icon with built in metabolic monitoring chart as a component of youth prescribed antipsychotic case records. Good documentation practice is a first step in determination of causality of antipsychotics induced metabolic syndrome. Appropriate strategies to a user-friendly electronic reminder system will be crucial to address on the mechanistic of documentation. [ABSTRACT FROM AUTHOR]

Objectives: Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.Methods: A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.Results: Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.Limitations: Small sample sizes, different index episodes and variety of outcome measures.Conclusion: Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted. [ABSTRACT FROM AUTHOR]

In this paper, we will discuss the pharmacologic properties of antipsychotics, including those that are the same in structure and those that differentiate one from another. We will bring to you how differential pharmacologic properties can explain differential efficacy and differential tolerability. We will review how to use plasma drug levels and long-acting injectables to enhance compliance early in the illness, and to manage both forms of treatment resistance (pharmacokinetic and pharmacodynamic failures). Through inadequate pharmacokinetic processes (poor absorption, rapid metabolism, enzymatic polymorphisms, etc.), antipsychotic plasma levels do not reach sufficient concentration. Pharmacodynamic treatment failure (receptor binding and sensitivity, post-receptor effects, etc.) is the inability to provide a significant effect on psychotic symptoms despite therapeutic plasma levels. Long-Acting Injectable (LAI) antipsychotics employ technology that can provide a useful treatment tool in the armamentarium of a modern psychopharmacologist. The pharmacologic properties of antipsychotics differentiate one from another and can help explain differences in efficacy and tolerability. Utilizing plasma drug levels can enhance understanding of treatment failures and lead to specific patient management strategies for best outcomes. This kind of personalized approach to antipsychotic dosage would mean a big shift in the treatment of psychiatric patients. [ABSTRACT FROM AUTHOR]

The present systematic review was aimed at critically summarizing the evidence about treatment-emergent manic/hypomanic and depressive switches during the course of bipolar disorder (BD). A systematic search of the MEDLINE, EMBASE, CINAHL, Web of Science, and PsycInfo electronic databases was conducted until March 24th, 2021, according to the P referred R eporting I tems for S ystematic Reviews and M eta- A nalyses (PRISMA) statement. Observational studies clearly reporting data regarding the prevalence of treatment-emergent mood switches in patients with BD were considered for inclusion. Thirty-two original studies met the inclusion criteria. In the majority of cases, manic switches were analyzed; only 3 papers investigated depressive switches in type I BD. Treatment-emergent mania/hypomania in BD subjects ranged from 17.3% to 48.8% and was more frequent with antidepressant monotherapy compared to combination treatment with mood stabilizers, especially lithium, or second-generation antipsychotics. A higher likelihood of mood switch has been reported with tricyclics and a lower rate with bupropion. Depressive switches were detected in 5–16% of type I BD subjects and were associated with first-generation antipsychotic use, the concomitant use of first- and second-generation antipsychotics, and benzodiazepines. The included studies presented considerable methodological heterogeneity, small sample sizes and comparability flaws. In conclusion, many studies, although heterogeneous and partly discordant, have been conducted on manic/hypomanic switches, whereas depressive switches during treatment with antipsychotics are poorly investigated. In BD subjects, both antidepressant and antipsychotic medications seems to play a role in the occurrence of mood switches, although the effects of different pharmacological compounds have yet to be fully investigated. [ABSTRACT FROM AUTHOR]

Weight gain and metabolic disturbances are frequent in people treated with second generation antipsychotics (SGA). We aimed to investigate the effect of SGAs on eating behaviors, cognitions and emotions, as a possible contributor to this adverse effect. A systematic review and a meta-analysis were conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Original articles measuring outcomes relating to eating cognitions, behaviours and emotions, during treatment with SGAs were included in this review. A total of 92 papers with 11,274 participants were included from three scientific databases (PubMed, Web of Science and PsycInfo). Results were synthesized descriptively except for the continuous data where meta-analyses were performed and for the binary data where odds ratios were calculated. Hunger was increased in participants treated with SGAs with an odds ratio for appetite increase of 1.51 (95% CI [1.04, 1.97]; z = 6.40; p < 0.001). Compared to controls, our results showed that craving for fat and carbohydrates are the highest among other craving subscales. There was a small increase in dietary disinhibition (SMD = 0.40) and restrained eating (SMD = 0.43) in participants treated with SGAs compared to controls and substantial heterogeneity across studies reporting these eating traits. There were few studies examining other eating-related outcomes such as food addiction, satiety, fullness, caloric intake and dietary quality and habits. Understanding the mechanisms associated with appetite and eating-related psychopathology changes in patients treated with antipsychotics is needed to reliably inform the development of effective preventative strategies. [ABSTRACT FROM AUTHOR]

Schizophrenia is a major psychiatric disorder with unknown aetiology. Recent evidence suggests a potential role for cytokines in its pathophysiology and that antipsychotic medication may alter this. While the aetiology of schizophrenia remains only partly understood, an altered immune function representing an important avenue of further discovery. In this systematic review and meta-analysis we focus on the specific effects of second generation antipsychotics risperidone and clozapine on inflammatory cytokines. A defined systematic search of PubMed and Web of Science databases was performed to identify relevant studies published between Jan 1900 and May 2022. After screening of 2969 papers, 43 studies (27 single-arm and 8 dual-arm) were included that consisted of a total of 1421 patients with schizophrenia in the systematic review. From these, twenty studies (4 dual-arm; 678 patients) had data available on which a meta-analysis could be carried out. Our meta-analysis showed a significant reduction of pro-inflammatory cytokines post-risperidone treatment in the absence of a similar association with clozapine. Subgroup analyses (First episode v chronic) demonstrated that duration of illness influenced the extent of cytokine alteration; risperidone treatment produced significant cytokine changes (lowered IL-6 and TNF-α) in chronic patients but not in first-episode psychosis (FEP) patients. Varying treatment effects on cytokines can be observed by the use of different antipsychotic drugs. The cytokine alterations post-treatment are influenced by the specific antipsychotic drugs and patient status. This may explain disease progression in certain patient groups and influence therapeutic choices in the future. [ABSTRACT FROM AUTHOR]

This meta-analysis examined the efficacy of available pharmacological and nonpharmacological interventions for irritability among youth with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorders (DBD), disruptive mood dysregulation disorder (DMDD), and/or severe mood dysregulation (SMD). Literature searches were conducted in October 2020, resulting in 564 abstracts being reviewed to identify relevant papers, with 387 articles being reviewed in full. A random effects model was used for the meta-analysis, with subgroup meta-regressions run to assess effects of study design, intervention type, medication class, and clinical population. A total of 101 studies were included (80 pharmacological, 13 nonpharmacological, 8 combined). Despite high heterogeneity in effects (I 2 = 94.3%), pooled posttreatment effect size for decreasing irritability was large (Hedges' g = 1.62). Large effects were found for pharmacological (g = 1.85) and nonpharmacological (g = 1.11) interventions; moderate effects were found for combined interventions relative to monotherapy interventions (g = 0.69). Antipsychotic medications provided the largest effect for reducing irritability relative to all other medication classes and nonpharmacological interventions. A large effect was found for youth with ASD (g = 1.89), whereas a medium effect was found for youth with ADHD/DMDD/DBD/SMD (g = 0.64). This meta-analysis provides a comprehensive review of interventions targeting persistent nonepisodic irritability among youth with various psychiatric disorders. Strong evidence was found for medium-to-large effects across study design, intervention type, and clinical populations, with the largest effects for pharmacological interventions, particularly antipsychotic medications and combined pharmacological interventions, and interventions for youth with ASD. [ABSTRACT FROM AUTHOR]

Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders. [ABSTRACT FROM AUTHOR]

Genetic factors can, to a certain extent, successfully predict the therapeutic effects, metabolism, and adverse reactions of drugs. This research field, pharmacogenomics, is well developed in oncology and is currently expanding in psychiatry. Here, we summarize the latest development in pharmacogenomic psychiatry, where results of several recent large studies indicate a true benefit and cost-effectiveness of pre-emptive genotyping for more successful psychotherapy. However, it is apparent that we still lack knowledge of many additional heritable genetic factors of importance for explanation of the interindividual differences in response to psychiatric drugs. Thus, more effort to further develop pharmacogenomic psychiatry should be invested to achieve a broader clinical implementation. A review of recent scientific papers reporting data from large cohort studies and randomized clinical trials containing pharmacogenomic information reveals that more efficient and cost-effective drug treatment of depression and schizophrenia can be obtained by genotype-guided decisions on the prescription of psychiatric drugs as compared with treatment as usual. Clinical implementation requires better prioritization using the best strategies for pharmacogenomically assisted drug treatment as well as improved and continuous education of psychiatrists. Much scientific effort should be dedicated to identifying the currently missing heritable genetic factors, which should in turn be used as additional tools for more successful pre-emptive genotyping in psychiatry, thereby further optimizing antidepressant and antipsychotic drug treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Rose bengal is simple and economical to used as fluorescent probe. • This method is reliable, fast and can be used directly in real samples. • It clarifies the mechanism of action between RB and antipsychotics. Risperidone, olanzapine and aripiprazole have good efficacy in schizophrenia. Monitoring the concentration of antipsychotics in patients is helpful to provide a precise medication administration. Although many detection techniques based on large instruments have been developed, they are expensive and cumbersome, which are not conducive to clinical promotion. In this paper, rose bengal (RB) was firstly used as a low-cost fluorescent probe for the detection of antipsychotic drugs. Under the condition of pH 3.9, there is a strong negative electrostatic potential region in RB, which attracts positively charged antipsychotic drugs. This property allows the halogen atoms and oxygen atoms of RB to act as hydrogen bond donors to molecularly bond with the H atoms of the antipsychotic drugs, forming a non-luminous complex. The fluorescence intensity showed a linear quench relationship with the increasing concentration of risperidone, olanzapine and aripiprazole with low detection limits of 103, 82.0 and 81.0 μg L−1, respectively. This fluorescent method has good selectivity and can be successfully utilized in detecting antipsychotic medications in human urine and pharmaceutical tablets. [ABSTRACT FROM AUTHOR]

• This meta-analysis was to explore the relationship between psychiatric medications and the risk of falls and fractures in people taking them. • Typical antipsychotics, atypical antipsychotics and antidepressants are associated with the risk of falls. • Typical antipsychotics and atypical antipsychotics were associated with the risk of fractures. • Atypical antipsychotics and typical antipsychotics may be the drugs with the highest risk of falls and fractures, respectively. • Quetiapine and class z drugs may be the drugs with the highest risk of falls and fractures, respectively. An association between psychiatric medications and falls and fractures in people taking them has been demonstrated, but which class or medication leads to the greatest risk of falls or fractures should be further investigated. The aim of this study was to compare and rank the magnitude of risk of falls and fractures due to different psychiatric medications. Eight databases were searched for this meta-analysis and evaluated using a frequency-based network meta-analysis. The results included a total of 28 papers with 14 medications from 5 major classes, involving 3,467,314 patients. The results showed that atypical antipsychotics were the class of medications with the highest risk of falls, and typical antipsychotics were the class of medications with the highest risk of resulting in fractures. Quetiapine ranked first in the category of 13 medications associated with risk of falls, and class Z drugs ranked first in the category of 6 medications associated with risk of fractures. The available evidence suggests that atypical antipsychotics and typical antipsychotics may be the drugs with the highest risk of falls and fractures, respectively. Quetiapine may be the medication with the highest risk of falls, and class Z drugs may be the medication with the highest risk of fractures. [ABSTRACT FROM AUTHOR]

There has been an ongoing debate regarding the forced use of antipsychotic medications and both the psychiatric and legal professions have reacted strongly to the growing debate. Within the penological context, cases such as Washington v. Harper, Riggins v. Nevada, and Sell v. United States established the framework for determining when antipsychotic medication may be forcibly administered. Medication decisions under the Sell and Riggins cases are to be approved at judicial hearings; whereas, administrative hearings are sufficient for Harper cases. Forensic psychiatrists are also given responsibility in making the legal decision of whether or not to forcibly treat a patient with psychotropic medication against his will. In making this critical decision, a significant factor that is often minimized is the cultural background of the patient. The purpose of this paper is to present cultural factors to be considered in forced medication. Focusing on the culture defense argument, a review of how the legal system has dealt with cultural implications of a case will be presented. This paper will then discuss cultural issues embedded in the assessment, diagnosis, and treatment of psychiatric patients by forensic psychiatrists who are called upon to make the decision of whether or not to force medicate a patient against his will. Lastly, recommendations and a framework for providing a culturally sensitive assessment during the decision to forcibly medicate a patient with psychotropic medication will be offered. [ABSTRACT FROM AUTHOR]

Individuals experiencing a first episode of psychosis are likely to respond well to treatment with antipsychotic medications. Of those treated for a first episode of schizophrenia, three out of four can expect to achieve remission. The question of how long antipsychotic medication should be continued has been a topic of heated debate in the field. Longitudinal studies of individuals diagnosed with a first episode of psychosis have reported that as many as 30% may be able to come off of medications without relapsing while treatment discontinuation studies have found that very few patients remain in remission off of medication. This paper reviews the literature on relapse rates following a first episode of schizophrenia and identifies factors that contribute to the discrepancies in the rates reported. These factors include sampling considerations, the distribution of psychiatric diagnoses, the duration of follow-up, the rate of medication discontinuation and the criteria used to define illness recurrence. We propose that individuals for whom the diagnosis of their first psychotic episode is determined with ongoing follow-up to be due to schizophrenia are at extremely high risk of relapse and should be advised to continue antipsychotic medication for the long-term. Those whose first episode of psychosis is determined to be due to other causes are also at high risk of illness recurrence off medications. Recommendations for maintenance treatment should be tailored to reflect the risk of relapse and sequelae of relapse associated with specific causes of first episode psychosis. [ABSTRACT FROM AUTHOR]

Aim: The aim of this paper is to determine clinical factors related to hostility and disturbing and aggressive behaviour and to examine the effect of medication on these behaviours in FEP.Methods: Data from phase I and II of the OPTiMiSE trial are used. Outcome measures are the hostility item of the Positive and Negative Syndrome Scale (PANSS P7) and the disturbing and aggressive behaviour domain of the Personal and Social Performance scale (PSP-D).Results: Moderate, severe or extreme hostility (PANSS P7 > 3) was present in 42 patients (9.4%). The PANSS P7 and PSP-D were low to moderate but significantly associated with the selected PANSS items: delusions, hallucinatory behaviour, excitement, tension, uncooperativeness, unusual thought content, impulsivity, and lack of judgement and insight. In a subsample of 185 patients (41.5%) with baseline PANSS P7 > 1, the PANSS P7 and PSP-D scores improved in the first 4 weeks of amisulpride treatment. This effect remained significant after controlling for baseline positive symptoms (PANSS P1-P6). No significant differences were found between olanzapine and amisulpride in the second phase of the trial.Conclusion: Clinical risk factors such as poor impulse control, uncooperativeness and excitement could help clinicians in detecting and treating hostile and aggressive behaviour in FEP. Amisulpride could be an effective antipsychotic choice in the treatment of FEP patients who express hostile or aggressive behaviour. Future research is needed to compare the effects of amisulpride and olanzapine on hostility in FEP during the first weeks of treatment. [ABSTRACT FROM AUTHOR]

Background: Differences between people with schizophrenia and psychiatrically healthy controls have been consistently demonstrated on measures of retinal function such as electroretinography (ERG), and measures of retinal structure such as optical coherence tomography (OCT). Since our 2015 review of this literature, multiple new studies have been published using these techniques. At the same time, the accumulation of data has highlighted the "fault lines" in these fields, suggesting methodological considerations that need greater attention in future studies.Methods: We reviewed studies of ERG and OCT in schizophrenia, as well as data from studies whose findings are relevant to interpreting these papers, such as those on effects of the following on ERG and OCT data: comorbid medical conditions that are over-represented in schizophrenia, smoking, antipsychotic medication, substance abuse, sex and gender, obesity, attention, motivation, and influences of brain activity on retinal function.Results: Recent ERG and OCT studies continue to support the hypothesis of retinal structural and functional abnormalities in schizophrenia, and suggest that these are relevant to understanding broader aspects of pathophysiology, neurodevelopment, and neurodegeneration in this disorder. However, there are differences in findings which suggest that the effects of multiple variables on ERG and OCT data need further clarification.Conclusions: The retina, as the only component of the CNS that can be imaged directly in live humans, has potential to clarify important aspects of schizophrenia. With greater attention to specific methodological issues, the true potential of ERG and OCT as biomarkers for important clinical phenomena in schizophrenia should become apparent. [ABSTRACT FROM AUTHOR]

Abstract: Background: Bipolar Disorder (BD) long-term treatment is aimed to prevent relapses associated with worsening cognitive impairment and chronicity. Available mood stabilizers, including lithium, fail to prevent relapses in about 40% of bipolar patients. Purpose of the present paper is to review the available data about the efficacy and tolerability of mood stabilizer plus antipsychotic combined treatments. Method: A research in the main database sources has been conducted to obtain an overview about the efficacy and tolerability of the combination of a mood stabilizer plus an antipsychotic in the long-term treatment of BD. Papers with different methodologies but having relapse prevention as main outcome have been included. Results: Despite the heterogeneity of studies in terms of methodology, almost all papers reported a major efficacy of combined treatments respect to mood stabilizer mono-therapies but lower tolerability. The antipsychotic that presents more evidence of efficacy in combination with mood stabilizers is quetiapine. Discussion: Combined treatments can be a valid option to improve relapse prevention in BD. However, the higher risk for side effects has to be taken into account and specific combinations should be preferred according to patients' medical comorbidity. [Copyright &y& Elsevier]

Abstract: Neurological soft signs (NSS) are minor neurological abnormalities that can be revealed by a clinical examination focused on sensory and motor information processing. NSS include overflow movements (OMs), which are defined as involuntary movements that may accompany the production of voluntary movements. OM is generally considered to be a characteristic feature of schizophrenia. White matter abnormalities might be involved in the pathogenesis of OMs. Dopamine receptors play a role in oligodendrocytes development. There is a direct link between antipsychotic agents that bind to dopamine receptors on oligodendrocytes and the development of oligodendrocytes and myelin formation. In this paper, we review the current knowledge of the effects of antipsychotic agents on NSS in schizophrenic patients. As a result of this critical review we hypothesize that the neuroleptic actions described in this paper could explain why antipsychotic agents have no effect on the resolution of NSS in patients with schizophrenia. [Copyright &y& Elsevier]

Background: Nonmedical prescription psychiatric drug use (NMPDU) is an increasing global health problem, with recent concern focusing on darknet cryptomarkets as sources of procurement. There is a shortage of evidence regarding comparative worldwide NMPDU trends, due in part to data collection difficulties. This problem is particularly marked for non-opioid drugs, particularly those psychiatric drugs which act on the central nervous system (CNS) and have high misuse potential and are associated with high levels of dependency and fatal overdose. This paper therefore has two goals: 1) to report on the kinds of psychiatric prescription drugs available on cryptomarkets, and 2) to use this data to uncover temporal and geographical trends in sales of these products, potentially informing policy regarding NMPDU more generally.Method: Digital trace data collected from 31 cryptomarkets in operation between September 2013 and July 2016 was analysed by country of origin descriptively and for trends in the sales for 7 psychiatric drug groupings, based on their main indication or intended use in psychiatric practice.Results: Sedatives (such as diazepam and alprazolam) and CNS stimulants (mainly Adderall, modafinil and methylphenidate) had the greatest share of sales, but usage and trends varied by location. The UK has high and rising levels of sedative sales, whilst the USA has the greatest stimulant sales and increasing sedative rates. Sales of drugs used in the treatment of opioid dependency are also substantial in the USA. The picture is less clear in mainland Europe with high sales levels reported in unexpected Central and Northern European countries. There is evidence of a move towards the more potent sedative alprazolam - already implicated as a source of problematic NMPDU in the USA - in Australia and the UK. Sales of drugs such as antidepressants, antipsychotics, mood stabilisers and antidementia drugs - all drugs with limited abuse potential - were negligible, indicating minimal levels of online cryptomarket procurement for self-medicating mental health problems.Conclusion: Predominantly, psychiatric drugs with potent sedative, stimulant or euphoriant effects are sold on cryptomarkets and this varies by country. With some caveats regarding the limitations of cryptomarket digital trace data taken into account, the study of trends of these products sold online over time may offer a novel and increasingly important window onto wider drug purchasing habits. [ABSTRACT FROM AUTHOR]

• Abnormal use of prior experience to interpret sensory information in schizophrenia. • Visual aftereffects measure influence of prior experience on perception. • Evidence for alterations of visual aftereffects in schizophrenia. • Significant variability in findings due to type of aftereffect and clinical factors. • Findings allow for mechanistic interpretations for altered visual aftereffects. Psychosis—a cardinal symptom of schizophrenia—has been associated with a failure to appropriately create or use stored regularities about past states of the world to guide the interpretation of incoming information, which leads to abnormal perceptions and beliefs. The visual system provides a test bed for investigating the role of prior experience and prediction, as accumulated knowledge of the world informs our current perception. More specifically, the strength of visual aftereffects, illusory percepts that arise after prolonged viewing of a visual stimulus, can serve as a valuable measure of the influence of prior experience on current visual processing. In this paper, we review findings from a largely older body of work on visual aftereffects in schizophrenia, attempt to reconcile discrepant findings, highlight the role of antipsychotic medication, consider mechanistic interpretations for behavioral effects, and propose directions for future research. [ABSTRACT FROM AUTHOR]

Abstract Pharmaceuticals and personal care products are emerging contaminants that are increasingly detected in surface waters around the world. Despite the rise in environmental detections, measured concentrations are still typically low, raising the importance of environmental risk assessments that focus on ecologically relevant sublethal endpoints, such as altered behavior. Neuroactive pharmaceuticals, like mental health medications, pain killers, etc., may be particularly potent in this regard as they are specifically designed to cause behavioral changes without causing physiologic impairment in mammalian systems. We screened 15 different popular neuroactive pharmaceuticals, ranging from antidepressants (including 3 major antidepressant metabolites), anxiety medications, and pain killers, under three different exposure scenarios (repeated, late acute and early transient exposure) to look for behavioral effects in larval zebrafish using the visual motor response (VMR). Drugs were screened at 0, 1, 10, and 100 μg/L in the repeated exposure scenario, and at 0 and 100 μg/L in the late acute and early transient exposure scenarios. Eight of the 15 compounds tested, specifically the antidepressants amitriptyline, fluoxetine, nor-fluoxetine, paroxetine, sertraline, nor-sertraline, venlafaxine, and the antipsychotic drug haloperidol decreased swimming activity by 25% to 40% under repeated exposure conditions. Five of the compounds (amitriptyline, fluoxetine, nor-fluoxetine, paroxetine, and sertraline) also significantly decreased activity by 17% to 31% in the late acute exposure paradigm. Three compounds (fluoxetine, paroxetine and venlafaxine) significantly altered swimming activity with early transient exposure, however creating a hyperactive response and increasing activity from 24% to 28%, while haloperidol significantly decreased activity by 31%. This paper is, to our knowledge, the first to screen so many neuroactive pharmaceuticals, including major metabolites, in parallel under multiple exposure conditions. We show that antidepressants most consistently alter VMR swimming activity. Additionally, we show that major antidepressant metabolites can potentially alter behavior as much as their parent compounds. Furthermore, we show that the magnitude and direction of behavioral effect is dependent on the exposure duration and period, indicating that a more diverse experimental approach might be needed to more accurately assess the risk these compounds pose to the environment. Highlights • 7 out of 10 antidepressants altered swimming behavior in zebrafish larvae. • 2 out of 3 metabolites tested elicited similar effects as parent compounds. • 2 of 15 compounds altered behavior in repeated, late, and early exposure scenarios. [ABSTRACT FROM AUTHOR]

Abstract Objectives To describe the modifications of delusions in schizophrenia after treatment with antipsychotics. To understand these modifications by linking them with some aspects of self-disorders. Method Presentation of six cases all defined as schizophrenia according to the DSM-5 and in remission according to validated scales after a course of antipsychotic medication. Demonstration, using a descriptive and retrospective approach, of the different clinical evolutions of delusions. Establishment of a link between delusions and some aspects of self-disorders. Results For each case, the antipsychotic induces an obvious change in the evolution of the delusion. The delusional themes are different for each patient, and, in some cases, remain present after treatment. All patients experience interpretativity. Schneinderian symptoms and self-disorders are present in each case but are unequally distributed, and respond differently to treatment. When these symptoms are most pronounced, delusional ideas are the most bizarre and persist after treatment. Discussion Antipsychotics have an effect on subjects' overall presentation, rather than on a single trait. These modifications are most noticeable in subjects' relationships with themselves, with others, and with the world. The key issues seem to be the connection between subject and delusion and the emergence of the "I." Conclusion The phenomenological exploration of the evolution of the delusion from the beginning of pharmacological treatment demonstrates its link with the overall evolution of the subject's relationship with the self, with others, and with the world. This paper demonstrates the interest in continuing the exploration of modifications to the self-induced by antipsychotics, in order to better understand the interaction between drugs and the psychopathology of schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: Schizophrenia is a serious mental disorder characterized by a heterogonous spectrum of clinical manifestations. Schizophrenia is basically incurable. The discovery of antipsychotic medications in the late 1940s has helped control some of the symptoms but has not reversed the course of the disorder and has had limited effect on the debilitating symptoms of the illness. In recent years brain stimulation technologies have emerged in the bio-scientific scenery. Deep brain stimulation now plays an important role in the treatment of many neurological disorders, and seems promising in treating depression. Optogenetics is a new technology that offers control over neuronal activity by turning on and off distinct neuronal populations. It has a great advantage over previous brain stimulation technologies in that it is accurate and specific to the neurons intended for activation and control. There is no evidence that brain stimulation has been investigated in schizophrenia patients. This possibility was discussed in a single commentary that proposed the hippocampus and nucleus accumbence as targets for DBS in schizophrenia, however it was emphasized that the neurophysiology and neuroanatomy of schizophrenia have not been elucidated to the extent that brain stimulation can be planned. In light of new optogenetic technology time is ripe to seriously consider optional targets of intervention in the brain of schizophrenia patients. Any such target should involve neuronal circuits (1) known to be relevant for schizophrenia, (2) involved in cognitive and brain functions that are disturbed in schizophrenia, and (3) relevant to alleged neuronal network mechanisms that are presumably damaged or malfunctioning in schizophrenia. This paper reviews the relevant literature and proposes that optogenetic interventions in schizophrenia should begin in the prefrontal cortex and the Globus-Pallidus Subthalamic nuclei systems. In the protocol for the prefrontal cortex, wide-arbore and chandelier inhibitory interneurons should be targets for optogenetic intervention and in the Globus-Pallidus Subthalamic nuclei the fast spiking neurons should be targets for optogenetic intervention. These subsystems are critical modulators of neural complexity which is directly relevant to connectivity organization in the brain. Schizophrenia is described as a disturbance of connectivity organization in the brain treatable by the relevant optogenetic interventions promoted in this paper. [Copyright &y& Elsevier]

Summary: Introduction: Bipolar depression poses a great burden on patients and their families due to its duration, associated functional impairment, and limited treatment options. Given the complexity of the disorder and the advances in treatment, a number of clinical guidelines, consensus statements and expert opinions were developed with the aim to standardize treatment and provide clinicians with treatment algorithms for every-day clinical practice. Unfortunately, they often led to conflicting conclusions and recommendations due to limitations of the available literature. As findings emerge from research literature, guidelines quickly become obsolete and need to be updated or revised. Many guidelines have been updated in the last 5years, after the last review of bipolar disorder (BD) treatment guidelines. Objective: The purpose of this work is to systematically review guidelines, consensus meetings and treatment algorithms on the acute treatment of bipolar depression updated or published since 2005, to critically underline common and critical points, highlight limits and strengths, and provide a starting point for future research Materials and methods: The MEDLINe/PubMed/Index Medicus, PsycINFO/PsycLIT, Excerpta Medica/EMBASE, databases were searched using “depression”, “bipolar”, “manic-depression”, “manic-depressive” and “treatment guidelines” as key words Results: The search returned 204 articles. Amongst them, there were 28 papers concerning structured treatment algorithms and/or guidelines suggested by official panels. After excluding those guidelines that were not performed by scientific societies or international groups and those published before 2005, the final selection yielded 7 papers When looking into guidelines content, the results indicate a trend to the gradual acceptance of the use of the atypical antipsychotic quetiapine as monotherapy as first-line treatment. Antidepressant monotherapy is discouraged in most of them, although some support the use of antidepressants in combination with antimanic agents for a limited period of time. Lamotrigine has become a highly controversial option. Conclusion: The management of bipolar depression is complex and should be differentiated from management of unipolar depression. Guidelines may be useful instruments for helping clinicians to choose and plan bipolar depression treatment by integrating the more updated scientific knowledge with every-day clinical practice and patient-specific factors; however, a further effort is needed in order to improve guidelines implementation in clinical practice. The latest updates on treatment guidelines for bipolar depression give priority to novel treatment approaches, such as quetiapine, over more traditional ones, such as lithium or antidepressants. Lamotrigine is a controversial option. [Copyright &y& Elsevier]

Abstract: The use of atypical antipsychotics is rapidly expanding in the management of bipolar disorder. This therapeutic class appears to have benefits across the spectrum of moods found in bipolar disorder, and a re-examination of the monoamine hypothesis is required. This paper reviews the evidence for the role of monoamines, and particularly dopamine, in bipolar depression and its implications in the treatment of patients, focusing upon the response to atypical antipsychotics. Relevant papers were identified undertaking a literature search using PubMed: preclinical and clinical studies that incriminate the dopaminergic system in bipolar depression, and recent controlled trials supporting the use of atypical antipsychotics, are reviewed. There is substantial evidence indicating that not only serotonin, but also dopamine may still play an important role as a mediator of antidepressant response in bipolar depression. A regionally selective balance between the dopamine and serotonin systems may account for the mood-stabilizing properties of these drugs, and in fact, a low D2 occupancy might be more relevant to bipolar depression than greater 5-HT2 action. This mechanism might correlate with the ability to induce neurogenetic effects. Hence, the greater the atypical profile, the more suitable for bipolar depression. Further studies are needed to confirm this hypothesis. [Copyright &y& Elsevier]

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In this paper, SLV310 is presented as a novel, potential antipsychotic displaying the interesting combination of potent dopamine D2 receptor antagonism and serotonin reuptake receptor inhibition in one molecule. As such, SLV 310 could be useful in treating a broad range of symptoms in schizophrenia. This paper describes the structure–activity relationship in a series of compounds leading to SLV310 (6b, 2-{4-[4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl]-butyl}-phthalimide) together with pharmacological data showing the unique profile of this compound. [Copyright &y& Elsevier]

Schizophrenia affects approximately 24 million people worldwide and clozapine is the most effective antipsychotic drug. Nevertheless, its use in therapy is limited due to adverse effects.Therapeutic drug monitoring is a clinical tool useful to reduce the clozapine toxicity. In the literature, papers showed how psychiatric disorders could be associated with low vitamin D levels, but a few studies focusing on its role in affecting clozapine exposure are available. A TDM repository was analyzed: clozapine and vitamin D levels measured with liquid chromatography were considered. 1261 samples obtained from 228 individuals were evaluated: 624 patients (49.5%) showed clozapine plasma levels in therapeutic range (350–600 ng/mL). Clozapine toxic plasma levels (>1000 ng/mL) were more present in winter (p = 0.025), compared to other seasons. Concerning vitamin D, a sub-analysis of 859 samples was performed: 326 (37.81%) were deficient (ng/mL), 490 (57.12%) had insufficient concentrations (10–30 ng/mL), while 43 (5.02%) had sufficient (>30 ng/mL) levels. A correlation between vitamin D and clozapine plasma levels (p = 0.007, Pearson coefficient=0.093) was observed. The role of seasonal variation in clozapine plasma exposure in psychiatric patients treated with clozapine was suggested. Further studies in larger cohorts are needed in order to clarify these aspects. [Display omitted] • Vitamin D in psychiatric patients treated with clozapine. • Clozapine therapeutic Drug Monitoring in treated patients. • Impact of seasonality in Vitamin D and clozapine plasma exposure. • Clozapine toxicity in treated patients and the role of seasonality. [ABSTRACT FROM AUTHOR]

Aggressiveness is observed in children and adolescents with various pathologies, most often antisocial conduct disorders. This paper focuses on these particular disorders. Pharmacological treatment is one option available to psychiatrists, other options being generally quite limited. Nevertheless, pharmacological treatment is complicated by numerous problems, such as the choice of medication, the definition of treatment targets, the therapeutic strategy to be conducted, and the management of compliance difficulties in subjects who are often unpredictible and poorly motivated. This article describes various chemical groups which are traditionally prescribed in conduct disorders (standard neuroleptics and lithium), as well as other drugs which controlled studies point to as possible alternatives : atypical neuroleptics and anti-convulsivant medication. Other substances are mentioned in this paper but we need to better target their according to the type of agressiveness involved, to combine them with molecules, and to better understand their long-terme effect. [Copyright &y& Elsevier]

Highlights • In schizophrenia, higher antipsychotic dose associated with smaller nucleus accumbens. • In affective psychoses, higher benzodiazepine dose associated with larger GM volumes. • Benzodiazepine use confounded some associations in schizophrenia. • Benzodiazepine effects on brain should be investigated further. • More studies on medication effects on brain in affective psychoses are needed. Abstract The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper is to provide evidence of the validity and reliability of the COMRADE scale (Combined Outcome Measure for Risk communication And treatment Decision making Effectiveness) in patients suffering from schizophrenia spectrum disorders.Method: 150 patients recruited at five mental health centers were assessed using a cross-sectional study design. The COMRADE, WAIS-S (therapeutic alliance) and TSQM (satisfaction with medication) scales were used.Results: Exploratory Factor Analysis identified three factors from the COMRADE (F1: "Risk communication"; F2: "Confidence in decision" and F3: "Knowledge of decisional balance") which explain 45.2, 8.5 and 6% of the variance, respectively. Statistically significant correlations were observed between the scores of the COMRADE subscales with the subscales of the WAI-S and the TSQM. The internal consistency observed for each of the factorial scores of the COMRADE were (Cronbach's alpha values) 0.90, 0.89 and 0.74, respectively.Conclusion: The COMRADE scale offers appropriate psychometric properties for its use as a measure of perceived patient involvement in the shared decision making process in antipsychotic treatment.Practice Implications: The use of the COMRADE measure in psychiatric clinical practice and in research studies provides an outcome measure of interventions from the shared decision making model. [ABSTRACT FROM AUTHOR]

Since the original description of side effects of neuroleptics, different terminologies and definitions for tardive dyskinesia (TD) and tardive syndrome (TS) have been used by different authors, and often these two terms have been used interchangeably. This paper proposes a nosology designed to define and clarify various terms and phenomenologies within the TS spectrum. We propose to use the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements, as well as to the analogous repetitive movements that can appear in the limbs, trunk, or pelvis. The repetitive, relatively rhythmic nature of the movements is the common denominator of this phenomenologic category. The term tardive syndrome refers to the spectrum of all persistent hyperkinetic, hypokinetic and sensory phenomenologies resulting from chronic dopamine receptor blocking agents (DRBA) exposure. Thus, TS is an umbrella term. When dystonia is the main feature of TS it is considered to be tardive dystonia (TDyst). Retrocollis appears to be the predominant form of cervical dystonia in this condition. Cranial dystonias, particularly oromandibular dystonia, are also common forms of TDyst. Tardive akathisia refers to the inability to remain still with an urge to move, giving the appearance of restlessness. It is a sensory phenomenon and a common and disabling form of TS. Unlike acute akathisia, tardive akathisia tends to occur late and persists after the drug is withdrawn. In tardive tourettism, the patient exhibits the features of Tourette syndrome with complex motor and phonic tics associated with premonitory urge and relief of tension after performing the tic behavior. Tardive tremor differs from the resting tremor seen in drug-induced parkinsonism in that it is mainly a postural and kinetic greater than resting tremor. Tardive pain has been reported in association with chronic use of DRBA's. The pain involved the mouth, tongue and the genital region. The patients tended to obsess over the pain and usually had some other form of motor tardive syndrome, either tardive dyskinesia, tardive akathisia or tardive dystonia. The term tardive parkinsonism has been proposed for those drug induced parkinsonism patients who have persistent symptoms following discontinuation of the DRBA. However, there is a strong possibility that the DRBA may have simply unmasked subclinical parkinsonism or that there is coincident Parkinson disease developing during the period the patient is taking the DRBA. [ABSTRACT FROM AUTHOR]

Objective: As a group, people with schizophrenia have a number of subtle anatomical abnormalities as well as physiological abnormalities that precede antipsychotic treatment. Some studies have also found shorter birth length or shorter adult height in people with schizophrenia compared to control subjects. We performed a systematic review and meta-analysis of studies of birth length and adult height in schizophrenia, following PRISMA guidelines (Prospero Registration # CRD42016043718).Data Sources: We searched the PsycInfo, Web of Science, and PubMed databases for articles published 1947-2016.Study Selection: Articles were included if they had data for patients diagnosed with schizophrenia and a matched control group of subjects without a psychotic disorder; both groups were measured for birth length and/or adult height (18years or older); and the paper was published in English.Data Extraction: One author extracted the data, which was verified by the other.Results: For adult height, six studies with 1,122 patients and 250,200 control subjects were included in analyses. There were six birth length studies, which included 984 patients and 976,296 controls. The patients did not differ from comparison subjects in birth length (effect size estimate=-0.03; CI: -0.09, 0.03), but adults were slightly shorter than comparison subjects (-0.15; -0.24, -0.06). In meta-regression of adult studies, the variables of first episode versus clinical sample, and population registry versus non-registry were not significant. Matching for several important variables was usually lacking in these studies.Conclusions: While there appears to be no difference in birth length between people with schizophrenia and comparison subjects, the former may be slighter shorter in adult life. The cause of such a discrepancy, if confirmed, is not clear, and lack of matching on potentially confounding variables undermines confidence in any conclusion. [ABSTRACT FROM AUTHOR]

Background: Aripiprazole is used relatively frequently in women with bipolar disorder or schizophrenia in childbearing years, owing to its efficacy and relatively favorable side effect profile. As is the case for other psychotropic medications, for ethical reasons, no prospective randomized placebo controlled trial to assess aripiprazole safety during pregnancy has ever been conducted. However, animal data are available and the amount of exposure and outcome data for human fetuses and infants has recently increased, providing published prospective safety data in relatively large numbers of pregnant women treated with aripiprazole. The aim of this study was to perform a systematic literature search and review to critically evaluate the available data on the use of aripiprazole during pregnancy, peripartum and lactation.Methods: PubMed, PsychInfo, and Cochrane Library were searched using the following search builder: (pregnancy OR pregnant OR gestation OR malformations OR perinatal OR reproduction OR organogenesis OR delivery OR breast-feeding OR lactation or peripartum or obstetric) AND aripiprazole. Reports that met the following pre-defined criteria were included in the present review: (1) published in English language in a peer-reviewed journal; (2) clearly defined use of aripiprazole during pregnancy and/or lactation and/or postpartum; (3) case report, case series, prospective, retrospective or cross-sectional studies. United States and European Medicine Agency prescribing information for aripiprazole were consulted as well and all the references of selected papers were cross checked for information pertaining to the use of aripiprazole during pregnancy, peripartum and lactation.Results: A total of 549 items published in a period ranging from 1995 to 2017, were retrieved from the search databases and reference cross check. One-hundred-fifty-three duplicate items were removed, 176 titles were deemed as not pertinent, 220 abstracts and 122 full-text articles were assessed for eligibility and 93 titles were included for qualitative synthesis. United States and European Medicine Agency prescribing information for aripiprazole were consulted and the selected manuscript references were cross checked. No randomized placebo controlled trial was found but relatively large prospective studies, large database studies, and several case reports and case studies were identified and summarized.Conclusions: As is the case for other antipsychotics, definitive evidence on aripiprazole reproductive safety is lacking, but newer safety data are relatively reassuring. In many cases, the potential benefits of aripiprazole for patients with bipolar disorder or schizophrenia outweigh the potential risks. [ABSTRACT FROM AUTHOR]

Background: Bipolar patients experience sleep disturbances during and between mood episodes. Yet the impact of sleep on treatment with different medications has not been fully explored. The purpose of this paper is to explore the potential impact of poor sleep at baseline on outcomes in a randomized effectiveness trial of quetiapine and lithium.Methods: The Bipolar CHOICE study was a 6-month, parallel group, multisite randomized controlled trial. Participants with bipolar disorder (N = 482; 59% female and age 18-70 years) received quetiapine or lithium. Patients were allowed to also receive adjunctive personalized treatments, which were guideline-informed, empirically-based medications added to treatment as needed. Medication changes were recorded as necessary clinical adjustments (NCA). Fisher's exact tests, mixed-regression models, and Mann-Whitney U tests were used to assess demographic and clinical characteristics as well as whether sleep disturbance would predict outcomes.Results: 63% of patients had baseline sleep disturbance. Individuals with sleep disturbance had worse bipolar illness severity, greater severity of depression, mania, anxiety, irritability, and psychosis, were less likely to have sustained response (17% vs. 29%; adjusted RR: 0.55, 95% CI: 0.38-0.78, p = 0.0006) and had more NCAs (median 0.71 vs. 0.59, p = 0.03).Limitations: Our findings were limited by how we defined sleep disturbance, and by how severity of sleep disturbance was assessed with one item with a non-sleep specific measure.Conclusions: Baseline sleep disturbance was associated with more severe bipolar symptoms and worse 6-month outcomes. Further research is warranted on improving sleep in bipolar disorder, especially the role of psychosocial interventions. [ABSTRACT FROM AUTHOR]

Abstract: Although common and severe, mixed states are rarely the subject of proper clinical trials. The aim of this paper is to systematically review data published in 2013 on the pharmacological treatment of mixed states. Methods: The Medline database was searched for 2013 publications using the following keywords: ‘treatment’; ‘mixed’; ‘bipolar’. Results: Medline search returned 118 results. Manual inspection of abstracts allowed selecting six papers for further review. The first meta-analysis of the efficacy of second-generation antipsychotics in mixed episodes, published in 2013, showed the efficacy of these agents. Other papers suggested that asenapine and olanzapine were efficacious for mixed episodes, with olanzapine being equally effective in patients with or without substance abuse. Aripiprazole and ziprasidone were reported to be efficacious and safe in treating manic/mixed episodes in children and adolescents. In another trial, Calcitonin was not found to be superior to placebo in treating manic/mixed episodes. Conclusion: Although data suggest that most agents efficacious for mania may also be efficacious for mixed episodes, further studies are needed to confirm this assumption. [Copyright &y& Elsevier]

Background: Cocaine abuse is a major public health issue due to its role in the HIV and hepatitis C virus (HCV) epidemics in North America. A significant area of concern among people who use cocaine (PWUC), injected or smoked, is their frequent misuse of prescription drugs, particularly psychotropic medication (PM), such as tranquilizers, sedatives, stimulants, and antipsychotics. This paper aims to describe and understand practices of PM use among PWUC in downtown Montreal.Method: Ethnographic methods including participant observation and semi-structured interviews were used in an iterative manner.Results: Two thirds of the 50 participants were male. They ranged in age from 20 to 60 and most were homeless. A significant proportion of them reported polydrug use patterns that included frequent concomitant opioid use (heroin and/or prescription opioids (PO)). Benzodiazepine-based tranquilizers and the atypical antipsychotic quetiapine were the most frequently used PM. Routes of PM administration were oral, nasal and, to a lesser degree, intravenous. Five main PM use practices were identified: 1) "downers" from cocaine high (benzodiazepines and quetiapine); 2) enhancers of heroin/PO effects (benzodiazepines); 3) reducers or suppressors of heroin/PO withdrawal symptoms (benzodiazepines); 4) enablers of a different type of "trip" (benzodiazepines); and 5) treatment for mental and physical problems (benzodiazepines and quetiapine).Conclusion: PM use practices showed several complementary functions that PM fulfill in a context of polydrug use. The soothing and stimulating effects of PM reinforce the patterns of drug use among participants, posing various risks including overdose, HIV/HCV transmission, PM dependence and accidents. The results highlight the need for clinicians to assess clients' substance use patterns when prescribing PM and to question PWUC about PM use. The findings also underline certain unmet service needs in relation to overdose, HIV/HCV and mental health prevention/treatment among cocaine users. [ABSTRACT FROM AUTHOR]

The aim of this paper is to provide a brief review of mitochondrial structure as it relates to function and then present abnormalities in mitochondria in postmortem schizophrenia with a focus on ultrastructure. Function, morphology, fusion, fission, motility, ΔΨmem, ATP production, mitochondrial derived vesicles, and mitochondria-associated ER membranes will be briefly covered. Pathology in mitochondria has long been implicated in schizophrenia, as shown by genetic, proteomic, enzymatic and anatomical abnormalities. The cortex and basal ganglia will be reviewed. In the anterior cingulate cortex, the number of mitochondria per neuronal somata in layers 5/6 in schizophrenia is decreased by 43%. There are also fewer mitochondria in terminals forming axospinous synapses. In the caudate and putamen the number of mitochondria is abnormal in both glial cells and neurons in schizophrenia subjects, the extent of which depends on treatment, response and predominant lifetime symptoms. Treatment-responsive schizophrenia subjects had about a 40% decrease in the number of mitochondria per synapse in the caudate nucleus and putamen, while treatment resistant cases had normal values. A decrease in mitochondrial density in the neuropil distinguishes paranoid from undifferentiated schizophrenia. The appearance, size and density of mitochondria were normal in the nucleus accumbens. In the substantia nigra, COX subunits were affected in rostral regions. Mitochondrial hyperplasia occurs within axon terminals that synapse onto dopamine neurons, but mitochondria in dopamine neuronal somata are similar in size and number. In schizophrenia, mitochondria are differentially affected depending on the brain region, cell type, subcellular location, treatment status, treatment response and symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Data from the literature suggests that some first episode psychosis (FEP) patients may recover without antipsychotic medication. There is however no reliable way to identify them. In a previous paper we found, in a cohort of 584 FEP patients, that those consistently refusing medication had poorer pre-morbid functioning, less insight, higher rate of substance use and poorer outcome. However, some medication refusers, had a favourable outcome. The study aim was to identify predictors of good short term outcome despite non-exposure to medication.Methods: The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 FEP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data on medication adherence was available in 584 patients. Among the 17.9% of patients who consistently refused medication over the entire treatment phase we compared patients who had a favourable symptomatic and functional outcome with those who did not.Results: Among patients who consistently refused medication, 41% achieved symptomatic remission and 33% reached functional recovery. Predictors of symptomatic remission were a better premorbid functioning level, higher education and employment status at baseline. Predictors of functional recovery were a shorter duration of the prodrome phase, less severe psychopathology at baseline and lower cannabis use.Conclusions: Despite limitations mainly linked to the fact that non-exposure to antipsychotic medication was based on patient's treatment refusal, this study identified some characteristics which may contribute to the identification of a sub-group of FEP patients who may have good short term outcome without antipsychotic treatment. [ABSTRACT FROM AUTHOR]

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28 days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29 ± 3.36 nm) with very high encapsulation efficiency (74.51 ± 1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48 h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6 months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48 h as compared to 8 h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28 days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects. [ABSTRACT FROM AUTHOR]

In 2020 the whole world focused on antivirus drugs towards SARS-CoV-2. Most of the researchers focused on drugs used in other viral infections or malaria. We have not seen such mobilization towards one topic in this century. The whole situation makes clear that progress needs to be made in antiviral drug development. The first step to do it is to characterize the potential antiviral activity of new or already existed drugs on the market. Phenothiazines are antipsychotic agents used previously as antiseptics, anthelminthics, and antimalarials. Up to date, they are tested for a number of other disorders including the broad spectrum of viruses. The goal of this paper was to summarize the current literature on activity toward RNA-viruses of such drugs like chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine. We identified 49 papers, where the use of the phenothiazines for 23 viruses from different families were tested. Chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine possess anti-viral activity towards different types of viruses. These drugs inhibit clathrin-dependent endocytosis, cell-cell fusion, infection, replication of the virus, decrease viral invasion as well as suppress entry into the host cells. Additionally, since the drugs display activity at nontoxic concentrations they have therapeutic potential for some viruses, still, further research on animal and human subjects are needed in this field to verify cell base research. Diagrammatic summary of phenothiazine derivatives antiviral activity. All of the phenothiazines (chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine) possess antiviral activity towards RNA viruses. These drugs inhibit clathrin-dependent endocytosis, cell-cell fusion, infection, replication of the virus, decrease viral invasion as well as suppress entry into the host cells. Image 1 • Phenothiazines possess antiviral activity towards RNA viruses. • An antiviral activity can be achieved below toxic serum concentration. • Phenothiazines are characterized by multidirectional points of action. [ABSTRACT FROM AUTHOR]

Approximately 30% of people with schizophrenia manifest a minimal response to conventional and atypical antipsychotic medications and manifest continuous symptoms of psychosis, with this condition referred to as “treatment resistant schizophrenia (TRS)”. There are several neurobiological consequences of continuous psychosis, including regional cortical atrophy and ventricular enlargement. Pharmacological treatments are available for TRS, with at least 1/3 of patients responding to treatment with clozapine. In this paper we review the evidence regarding the course of treatment resistant schizophrenia, as well as changes in brain structure and function in psychosis and on the possible role of clozapine treatment in altering cortical deterioration in patients with TRS. [ABSTRACT FROM AUTHOR]

Objective: The use of dopaminergic antagonist antipsychotics is associated with hyperprolactinemia, but some studies have found increased prolactin concentrations in antipsychotic-naive patients with schizophrenia and related disorders. We conducted a systematic review and meta-analysis of studies of prolactin in antipsychotic-naïve patient with these disorders (PRISMA No. CRD42015016337).Data Sources: PubMed (Medline), PsycInfo, and Web of Science were searched for articles from 1950 to the present in English.Study Selection: Seven studies of males (N=141 for patients, N=191 for control subjects) and five studies of females (N=67 and N=116) met criteria for inclusion: data on blood prolactin concentrations for both control subjects and antipsychotic-naive patients with schizophrenia or a related disorder, with data available separately for males and females.Data Extraction: Data was extracted from the papers by one author and independently verified by a second.Results: The mean effect size for males was 1.02 (95% CI, 0.77, 1.26; p<0.001) and 0.43 for females (95% CI 0.11, 0.76; p<0.01). Meta-regression analyses for age, smoking, body mass index (BMI), year of publication, and cortisol were not significant. Funnel plots did not suggest the presence of a publication bias.Conclusions: Our meta-analyses found significantly increased prolactin levels in both male and female antipsychotic-naïve patients with schizophrenia and related disorders. The small number of studies and limited matching for potentially confounding variables in some of the studies were limitations of this analysis. Prolonged hyperprolactinemia may lead to sexual dysfunction and osteoporosis, and some antipsychotics cause additional elevation of prolactin concentrations. [ABSTRACT FROM AUTHOR]

Second-generation antipsychotics have demonstrated efficacy for patients with schizophrenia but are associated with wide-ranging side effects. Brexpiprazole, a serotonin-dopamine activity modulator, has demonstrated efficacy in adult patients with schizophrenia. This paper provides an overview of the safety and tolerability of brexpiprazole in patients with schizophrenia through examination of pooled safety data from one Phase 2 and two Phase 3 6-week, short-term studies, and two open-label, 52-week, long-term studies. In the short-term studies, there were no reports of treatment-emergent adverse events (TEAEs) with an incidence≥5% and twice that of placebo in patients treated with brexpiprazole 2-4mg. In the long-term studies, TEAEs reported by ≥5% of patients were schizophrenia (10.7%), insomnia (8.0%), weight increase (7.7%), headache (6.0%), and agitation (5.2%). Akathisia rates were low in the short- (5.8%, pooled brexpiprazole group) and long-term studies (4.6%). Sedation rates were low in the short- (2.3%, pooled brexpiprazole group) and long-term studies (0.9%). Mean body weight increase was 1.1kg in both short- and long-term studies. For all studies, changes from baseline to last visit in laboratory parameters, electrocardiogram values, and vital signs were small and not clinically relevant. Changes in lipid profiles or other metabolic parameters were also small. Collectively, these studies suggest that brexpiprazole was well tolerated, with a favorable safety profile that does not exhibit significant rates of important adverse events that can be seen with existing antipsychotics (akathisia, sedation, weight gain, or QTc prolongation), and therefore may provide a useful treatment option for patients with schizophrenia. ClinicalTrials.gov: NCT00905307; NCT01396421; NCT01393613; NCT01649557; NCT01397786. [ABSTRACT FROM AUTHOR]

Objective There are no handbook or recommendations for the use of pharmacological agents to treat neurobehavioral disorders after traumatic brain injury (TBI). This work proposes a systematic review of the literature and a user guide on neuroleptics, antidepressants, beta-blockers, mood stabilizers and other medications for irritability, aggressiveness, agitation, impulsivity, depression, apathy… Method Steering, working and reading groups (62 people) were formed under the control of the French High Authority for Health (HAS) in collaboration with the SOFMER scientific society (French Society of Physical and Rehabilitation Medicine). Articles were searched by HAS officers in the Medline database from 1990 to 2012, crossing TBI and pharmacological agents. The HAS method to select, read and analyze papers is close to the PRISMA statements. Results Out of 772 references, 89 were analyzed, covering a total of 1306 people with TBI. There is insufficient evidence to standardize drug treatments for these disorders. There are however some elements to establish consensus recommendations for good clinical practice. Propranolol can improve aggression (B grade). Carbamazepine and valproate seem effective on agitation and aggression and are recommended as first line treatment (Expert Consensus [EC]). There is no evidence of efficacy for neuroleptics. Their prescription is based on emergency situation for a crisis (loxapine) but not for long-term use (EC). Antidepressants are recommended to treat depression (EC) with a higher standard of proof for Selective Serotonin Reuptake Inhibitors (SSRI, grade B). Other products are described. Conclusion The choice of treatment depends on the level of evidence, target symptoms, custom objectives, clinical experience and caution strategies. [ABSTRACT FROM AUTHOR]

Background: Several studies have analyzed prescription patterns for bipolar disorder, but few have for acute mania. Treatment strategies in this complex domain change over time and do not always follow evidence-based guidelines.Methods: Prescription data of in-patients suffering from acute mania in the time period from 2005 to 2012 were obtained from the database of the Drug Safety Program in Psychiatry (Institut für Arzneimittelsicherheit in der Psychiatrie; AMSP). Data were collected on two index dates per year. Changes over time were analyzed comparing the time periods 2005/06 and 2011/12.Results: Among 1650 patients (mean ±SD; age: 48.9±14.91 years; 53.1% females) 54.1% received anticonvulsants, 74.5% second-generation antipsychotics (SGAs), 17.8% first-generation antipsychotics (FGAs), 29.1% lithium, 44.1% benzodiazepines and 14.5% antidepressants. Prescription of SGAs increased from 70% to 79% (p=0.005), while prescription of FGAs and anticonvulsants decreased from 19% to 13% (p<0.05) and 59% to 46% (p<0.001), respectively. Only 30% of patients received monotherapy with one mood stabilizer. We observed an impact of gender, age and psychotic symptoms on treatment strategy. 36.8% of the women≤40 years received valproate.Limitations: Follow-up data are missing and no differentiation between acute and maintenance treatments could be made due to the cross-sectional design. Additionally, our findings do not necessarily translate to outpatients or to other countries.Conclusions: Combination therapies represent standard clinical practice. Though many results reflect clinical necessity, the high number of antidepressant prescriptions or valproate use in women of child-bearing age should be judged critically. Further prospective studies should focus on real-world prescription practice in acute mania to evaluate efficacy and safety of common practice. This paper is dedicated to Prof. Dr. Hanns Hippius on the occasion of his 90th birthday. [ABSTRACT FROM AUTHOR]

[Display omitted] • Comparative analysis of the affinity interaction between two typical antipsychotics and HSA. • Combined multispectral and electrochemical methods compared the binding intensity of their interactions. • The two antipsychotics caused significant perturbations to the structure of the HSA. • Molecular docking demonstrated the existence of multiple forces during the interaction. Psychiatric disorders are common diseases with a high prevalence. Currently, increasing focus on the treatment of psychiatric disorders has driven the development and investigation of antipsychotic drugs. In this paper, two classical antipsychotic drugs risperidone (RIP) and paliperidone (PIP) were selected as research subjects to explore their action mechanism with biological macromolecule human serum albumin (HSA). Combined UV spectroscopy and time-resolved fluorescence spectroscopy results showed that the quenching of HSA by RIP/PIP was a static process, and this result was further confirmed by temperature-dependent experiments, while hydrogen bonding, electrostatic forces and hydrophobic forces existed in the above process. Furthermore, synchronous fluorescence spectroscopy, three-dimensional fluorescence spectroscopy and circular dichroism (CD) spectroscopy experiments demonstrated the effect on HSA before and after the addition of RIP/PIP. Electrochemical experiments results determined that K a of HSA and RIP/PIP system was 1.52 × 104 M−1–2.85 × 104 M−1. According to the competition experiments and molecular docking indicating RIP/PIP bound to site I of HSA. Finally, these results provided reliable information for the development of antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Background A number of data show the negative role of duration of untreated illness (DUI) on outcome in mood disorders, but no investigation has been carried out about the impact of this variable in bipolar disorder (BD) with psychotic symptoms. Clinical experience shows that many bipolar patients with psychotic symptoms receive other diagnoses and often are chronically treated with first generation antipsychotics, with the effect to reduce duration of untreated psychosis/untreated episode with psychotic symptoms (DUP), but not DUI. Purpose of the study was to define the rate of misdiagnosis and the impact of DUP/DUI on outcome of bipolar patients with psychotic symptoms. Method Clinical information (DUP, DUI, first received diagnosis) about bipolar outpatients with psychotic symptoms ( N =240) were extrapolated through a retrospective review of the clinical charts, Lombardy database and, if necessary, through clinical interviews with patients and their relatives. Outcome measures included psychiatric and substance abuse comorbidity, occupational status, Global Assessment of Functioning (GAF), number of hospitalizations and of suicidal attempts, number of depressive/manic recurrences. Patients were divided in two groups according to the DUP (1 year) and DUI (8 years) median, and the groups were compared through analyses of variance (ANOVAs) for continuous variables or χ 2 tests for dichotomous ones. Multivariate analysis of variance (MANOVA) with duration of illness as covariate was then performed to eliminate the effect of this variable. Finally, binary logistic regressions were performed considering age at onset, DUI, DUP as independent variables and outcome variables as dependent ones (presence of hospitalizations/suicidal attempts, GAF scores<50, occupational status). Results Most of patients (61.5%) received a first diagnosis different from BD with the most frequent DSM-diagnosis being delusional disorder (17.9%). Patients with longer DUP were not different in outcome measures with respect to patients with shorter DUP. Patients with a DUI >8 years presented higher number of hospitalizations ( F =6.04, p =0.015), higher number of manic recurrences ( F =5.25, p =0.023), higher number of depressive recurrences ( F =7.13, p =0.008) and lower GAF scores ( F =17.74, p <0.001). Statistical significance persisted for number of hospitalizations ( p <0.001) and GAF scores ( p =0.003) after MANOVA. Finally binary logistic regression showed that a longer DUI was predictive of GAF scores<50 ( F =17.74, p <0.001). Discussion More than half of bipolar patients with psychotic symptoms receive a different diagnosis at first contact with psychiatric services. DUI (but not DUP) is a predictor of outcome in bipolar patients with psychotic symptoms. This indicates that an early diagnosis and proper treatment with a mood stabilizer (or an atypical antipsychotic with mood stabilizing effects) may improve long-term outcome of these patients. In the light of the naturalistic design of the present paper, these results have to be considered as preliminary and have to be confirmed by prospective controlled studies. [ABSTRACT FROM AUTHOR]