Comparative Analysis of the Pre- and Post-Medication Effects of Antipsychotic Agents on the Blood-Based Oxidative Stress Biomarkers in Patients with Schizophrenia: A Meta-Analysis.

OBJECTIVE: Studies have shown that oxidative stress (OS) is related to the pathophysiology of schizophrenia (SCZ), but whether antipsychotics can induce OS has not been investigated well. Moreover, antipsychotics have differential effects on the OS level modulation, i.e., different types of antipsychotics have different effects on the cellular antioxidants or pro-oxidants. METHODS: We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and investigated the OS indicators including both enzymatic and nonenzymatic markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), vitamin C, etc., of SCZ patients at baseline and follow-up of mono-medication. RESULTS: Twenty studies met the inclusion criteria, with a total of 1162 patients enrolled at baseline, and 1105 patients completed the follow-up. OS markers were changed after a period of antipsychotic treatment in SCZ patients. The GPx activity and MDA level decreased in the whole blood (P<0.05), also the serum MDA level decreased (P<0.05). For the first-episode SCZ patients, the activity of GPx and the level of MDA decreased, while the level of vitamin C increased (all P<0.05). The levels of MDA in patients receiving atypical antipsychotics decreased (P<0.05), while the level of GSH in patients with typical antipsychotics decreased (P=0.05). CONCLUSION: Antipsychotic medication may cause changes in the levels of OS markers in different blood samples of SCZ patients. However, the available studies might not be sufficient to reveal the underlying facts accurately due to the poor quality of experimental designs in the published literature.

Comparative Study of Extrapyramidal Side Effects, Sexual Dysfunctions and Hyperprolactinaemia Using Typical and Atypical Antipsychotic Medications Among Patients with Schizophrenia in Maiduguri.

Background: Extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia are major side effects with the use of antipsychotic medications that impede treatment adherence leading to relapse, increased cost of care and rehospitalization among patients with schizophrenia on antipsychotic medications. The study aims to compare the prevalence of extra-pyramidal side effects (EPSE), sexual dysfunctions (SD) and hyperprolactinaemia (HPRL) among patients with schizophrenia spectrum disorders on typical and atypical antipsychotic medications. The secondary aim is to determine if any associations exist between extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia. Methodology: A cross-sectional hospital-based survey involving 209 patients with schizophrenia were interviewed with structured instruments for the assessment of sexual dysfunction, EPSE and the estimation of serum prolactin was done using Enzyme-linked Immunosorbent Assay. Frequencies and Chi-square analysis were used to compare differences in EPSE, SD & HPRL. Results: The study revealed non-statistically significant differences as a group between typical and atypical antipsychotic medication in terms of extra-pyramidal side effects, sexual dysfunction and hyperprolactinaemia. However, a significant association was observed when individual drugs were compared with haloperidol causing the highest frequency of hyperprolactinaemia (χ 2 = 14.9, P = 0.011). A significant relationship between sexual dysfunction and hyperprolactinaemia, sexual dysfunction and extra-pyramidal side effects as well as extra-pyramidal and hyperprolactinaemia was found when individual items for sexual functionin were used. Conclusion: The significant relationships between sexual dysfunction only in the domains of sexual desire and arousal with hyperprolactinaemia and extrapyramidal side effects as well as hyperprolactinaemia with extrapyramidal side effects point to a common anti-dopaminergic activity of antipsychotics via different pathways. Prospective studies among a larger sample of patients with schizophrenia are needed to unfold these relationships.

Possible involvement of apoptosis in the antipsychotics side effects: A mini-review.

Antipsychotics are used in the treatment of schizophrenia and other psychiatric disorders. Generally, they are divided into typical and atypical ones, according to the fact that atypical antipsychotics induce fewer side effects and are more effective in terms of social and cognitive improvements. Their pharmacological effects are mediated via broad range of receptors that consequently influence different cellular signalling pathways. Antipsychotics produce undesirable side effects that range from relatively minor to life threatening. In vitro and in vivo studies have pointed to neurotoxic effect exerted by some antipsychotics and have shown that apoptosis might play role in some side effects induced by antipsychotics, including tardive dyskinesia, weight gain, agranulocytosis, osteoporosis, myocarditis, etc. Although cumulative data have suggested safety of atypical antipsychotics use during pregnancy, some of them have been shown to induce apoptotic neurodegenerative and structural changes in fetal brains with long-lasting impact on cognitive impairment of offspring. Typical antipsychotics seem to be more cytotoxic than atypical ones. Recently, epidemiological studies have shown lower incidence of cancer in schizophrenic patients that suggest the ability of antipsychotics to suppress risk of cancer development. Some antipsychotics have been reported to inhibit cancer cell proliferation and induce their apoptosis. Therefore, antipsychotics apoptotic effect may be used as a tool in the treatment of some types of cancer, especially in combinatorial therapies. In this mini-review, we focused on pro- and antiapoptotic or 'Dr. Jekyll and Mr. Hyde' effects of antipsychotics, which can be involved in their side effects, as well as their promising therapeutic indications.

Hemodynamic Impact of Drug Interactions With Epinephrine and Antipsychotics Under General Anesthesia With Propofol.

OBJECTIVE: Antipsychotic drugs exhibit α-1 adrenergic receptor-blocking activity. When epinephrine and antipsychotic drugs are administered in combination, ß-2 adrenergic effects are thought to predominate and induce hypotension. This study aimed to assess hemodynamic parameters in patients regularly taking antipsychotics who were administered epinephrine-containing lidocaine under general anesthesia in a dental setting. METHODS: Thirty patients taking typical and/or atypical antipsychotics and scheduled for dental procedures under general anesthesia were enrolled. Five minutes after tracheal intubation, baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and percutaneous oxygen saturation (SpO2) measurements were taken. The SBP, DBP, HR, and SpO2 measurements were repeated 2, 4, 6, 8, and 10 minutes after the injection of 1.8 mL of 2% lidocaine (36 mg) with 1:80,000 epinephrine (22.5 mcg) via buccal infiltration. RESULTS: Differences between the baseline measurements and those of each time point were analyzed using Dunnett test, and no statistically significant changes were observed. CONCLUSIONS: Our findings demonstrate that the use of epinephrine at a clinically relevant dose of 22.5 mcg for dental treatment under general anesthesia is unlikely to affect the hemodynamic parameters of patients taking antipsychotic medications.

Involvement of Gut Microbiota in Schizophrenia and Treatment Resistance to Antipsychotics.

The gut microbiota is constituted by more than 40,000 bacterial species involved in key processes including high order brain functions. Altered composition of gut microbiota has been implicated in psychiatric disorders and in modulating the efficacy and safety of psychotropic medications. In this work we characterized the composition of the gut microbiota in 38 patients with schizophrenia (SCZ) and 20 healthy controls (HC), and tested if SCZ patients with different response to antipsychotics (18 patients with treatment resistant schizophrenia (TRS), and 20 responders (R)) had specific patterns of gut microbiota composition associated with different response to antipsychotics. Moreover, we also tested if patients treated with typical antipsychotics (n = 20) presented significant differences when compared to patients treated with atypical antipsychotics (n = 31). Our findings showed the presence of distinct composition of gut microbiota in SCZ versus HC, with several bacteria at the different taxonomic levels only present in either one group or the other. Similar findings were observed also depending on treatment response and exposure to diverse classes of antipsychotics. Our results suggest that composition of gut microbiota could constitute a biosignatures of SCZ and TRS.

Extrapyramidal Side Effects in a Patient with Alcohol Withdrawal Symptoms: A Reflection of Quality of the Mental Health Care System.

BACKGROUND: The burden of substance use disorders is increasing in most countries in sub-Saharan Africa. Individuals with substance use disorders (eg, alcohol use disorder) are at high risk of manifesting extrapyramidal side effects or extrapyramidal symptoms (EPS) during treatment of alcohol-induced mental illness symptoms especially psychosis. EPS management poses a challenge since some of the drugs used for treating EPS have addictive properties. The knowledge about EPS diagnosis and treatment is not well distributed across the health system, with health workers at lower health facilities having least awareness. The present case gives details of a patient who developed EPS during the management of alcohol withdrawal symptoms. CASE DETAILS: Following cessation of alcohol use, a 54-year-old man with alcohol use disorder presented with a one-week history of visual, auditory and tactile hallucinations, illusions, insomnia, extreme fear and irritability. He was managed with several daily doses of intramuscular chlorpromazine 100 mg, whenever he woke up aggressive from sedation from a peripheral health facility. Four days after his admission, he became mute, stiff, immobile, triple-flexed, tremulous and was drooling saliva. He was referred to a secondary facility for further management while on antipsychotic medication. Finally, he was referred to a tertiary facility, managed with tablets of benzhexol 5 mg twice daily and intravenous diazepam 20 mg per day. Daily follow-up was done using the extrapyramidal symptom rating scale (ESRS) for EPS. EPS symptoms resolved ten days after initiation of treatment. CONCLUSION: EPS among individuals with addictive disorders poses a challenge in its management, especially in countries where the mental health care system is not well developed at lower-level health facilities. The mental health system has to prepare sustainable interventions to properly manage EPS among the growing population of individuals with addictive disorders through strengthening the mental health policy by training and equipping all health providers with knowledge and skills in managing EPS, increasing finances allocated for mental health and controlling the production and use of addictive substances.

Behavioral and Psychological Symptoms in Dementia (BPSD) and the Use of Antipsychotics.

Dementia affects about 47 million people worldwide, number expected to exponentially increase within 30 years. Alzheimer's disease (AD) is the most common dementia type, accounting on its own for almost 70% of all dementia cases. Behavioral and psychological symptoms (BPSD) frequently occur during the disease progression; to treat agitation, aggressiveness, delusions and hallucinations, the use of antipsychotic drugs should be limited, due to their safety issues. In this literature review regarding the use of antipsychotics for treating BPSD in dementia, the advantages and limitation of antipsychotic drugs have been evaluated. The available medications for the management of behavioral and psychological symptoms are the antipsychotics, classed into typical and atypical, depending on their action on dopamine and serotonin receptors. First generation, or typical, antipsychotics exhibit lack of tolerability and display a broad range of side effects such as sedation, anticholinergic effects and extrapyramidal symptoms. Atypical, or second generation, antipsychotics bind more selectively to dopamine receptors and simultaneously block serotonin receptors, resulting in higher tolerability. High attention should be paid to the management of therapy interruption or switch between antipsychotics, to limit the possible rebound effect. Several switching strategies may be adopted, and clinicians should "tailor" therapies, accounting for patients' symptoms, comorbidities, polytherapies and frailty.

Haloperidol elicits oxidative damage in the brain of rats submitted to the ketamine-induced model of schizophrenia.

The present study aims to evaluate the effects of haloperidol, an important first-generation antipsychotic, on the antioxidant system parameters in the brain of animals subjected to a model of schizophrenia induced by ketamine. Adult rats intraperitoneally received saline (1 mL/kg) or ketamine (25 mg/kg body weight) for 15 days, and saline or haloperidol (0.1 mg/kg body weight) via gavage once a day, between the 9th and 14th days. In the frontal cortex, hippocampus, and striatum, assessments of lipid (4-hydroxy-2-nonenal and 8-isoprostane levels) and protein (protein carbonyl content) oxidative damage were conducted. It was also measured the glutathione peroxidase and glutathione reductase activities in the same cerebral structures. Increases in the 4-hydroxy-2-nonenal and 8-isoprostane levels were detected in rats receiving haloperidol and ketamine. An increase in the carbonyl content was also observed in animals receiving ketamine, haloperidol, or a combination thereof. In animals receiving the antipsychotic, there was a decrease in the activity of the enzymes. Therefore, both ketamine and haloperidol induced oxidative damage. A possible energy dysfunction or a haloperidol effect targeting the glutathione enzymes, and then disrupting the redox homeostasis in neurons, could not be ruled out, although further studies are required to confirm or refute a direct interaction.

Stroke Risk Among Elderly Users of Haloperidol and Typical Antipsychotics Versus Atypical Antipsychotics: A Real-World Study From a US Health Insurance Claims Database.

BACKGROUND: We estimated stroke risk associated with new exposure to haloperidol, or any typical antipsychotic, versus atypical antipsychotic among patients aged ≥65 years regardless of dementia status. METHODS: IBM MarketScan Medicare Supplemental Database data (January 1, 2001 to December 31, 2017) were used. Stroke risk for new users of typical antipsychotics (T1 cohort) or haloperidol (T2 cohort) was compared with new users of atypical antipsychotics (C1 cohort) aged ≥65 years. Crude incidence rate (IR) and incidence proportion of stroke were estimated within each cohort and gender subgroup. Three propensity score (PS) matching strategies were employed: Unadjusted (crude), Sentinel PS replication, and a large-scale regularized regression model (adapted PS). RESULTS: Overall, 36,734 (T1), 24,074 (T2), and 226,990 (C1) patients were included. Crude IRs for stroke per 1000 person-years were 17.67 (T1), 23.74 (T2), and 14.17 (C1). In preplanned analyses, PS-matched calibrated hazard ratio (cHR) for stroke T1 versus C1 cohort was 1.08 (95% calibrated confidence interval [cCI] = 0.75, 1.55) with Sentinel PS strategy and 1.31 (95% cCI = 1.07, 1.60) with adapted PS strategy. The cHR for stroke in patients of T2 versus C1 was 1.69 (95% cCI = 1.08, 2.75) with Sentinel PS strategy and 1.45 (95% cCI = 1.17, 1.80) with adapted PS strategy. CONCLUSION: Stroke risk in elderly new users of haloperidol was elevated compared to new users of atypical antipsychotics and was elevated for typical antipsychotics using the adapted PS strategy.

The relationship between atypical antipsychotics drugs, QT interval prolongation, and torsades de pointes: implications for clinical use.

Introduction: Increased mortality has been observed in patients with mental health disorders. Specifically, exposure to antipsychotic medications conveys a greater than 2 fold risk of sudden death, thought to be mediated through effects on QT prolongation and risk of torsades de pointes.Areas covered: We review the association between antipsychotic drugs and sudden cardiac death, the physiologic basis for these associations, assessment of patients at risk, and strategies to minimize risk of sudden cardiac death.Expert opinion: Despite the prevalence of antipsychotic medication use for many decades, there remain considerable challenges in reducing the associated risk of sudden cardiac death. A structured algorithm that incorporates patient clinical factors and antipsychotic drug factors may improve risk assessment and reduce the risk of adverse cardiac events. Future advancements in genetics and artificial intelligence may allow for enhanced risk stratification and predicting response (efficacy and adverse effects) to therapy.

[Typical and atypical antipsychotics: how significant are the differences?] / Tipichnye i atipichnye antipsikhotiki: naskol'ko sushchestvenny razlichiia?

A number of frequently discussed issues of clinical psychiatry include comparing the advantages and disadvantages of typical and atypical antipsychotics. It is believed that atypical antipsychotics are less likely to cause extrapyramidal disorders and have a more significant effect on the negative symptoms of schizophrenia compared to typical drugs. However, many randomized controlled and cohort studies, as well as systematic reviews and meta-analyses carried out on their basis, allow questioning the superiority of second-generation antipsychotics over their predecessors, in particular in terms of tolerability. Current scientific evidence provides sufficient evidence for the clinical use of chlorpromazine and other traditional antipsychotics, along with more recent medicines.

Risk factors for pneumonia in patients with schizophrenia.

AIM: Pneumonia is a major cause of death in patients with schizophrenia. Preventive strategies based on identifying the risk factors are needed to reduce pneumonia-related mortality. This study aimed to clarify the risk factors for pneumonia in patients with schizophrenia. METHODS: We retrospectively reviewed the clinical files of consecutive patients with schizophrenia admitted to Tokyo Metropolitan Matsuzawa Hospital during a four-year period from January 2014 to December 2017. We analyzed the clinical differences between patients with and without pneumonia. RESULTS: Of the 2209 patients enrolled, 101 (4.6%) received the diagnosis of pneumonia at the time of hospital admission while 2108 (95.4%) did not have pneumonia. Multivariable analysis to determine the risk factors related to pneumonia showed that the use of atypical antipsychotics had the highest odds ratio among the predictive factors (2.7; 95% confidence interval [CI] 1.0-17.7; P = 0.046), followed by a total chlorpromazine equivalent dose ≥600 mg (2.6; 95% CI 1.7-4.0; P < 0.001), body mass index <18.5 kg/m2 (2.3; 95% CI 1.6-3.6; P < 0.001), smoking history (2.0; 95% CI 1.3-3.1; P < 0.001), and age ≥50 years (1.7; 95% CI 1.2-2.6; P = 0.002). CONCLUSIONS: We found that advanced age, underweight, smoking habit, use of atypical antipsychotics, and large doses of antipsychotics were risk factors for pneumonia in patients with schizophrenia. Among these factors, it was unclear whether the use of antipsychotics was a direct cause of pneumonia due to is uncertain because our retrospective study design. However, our result might be a good basis of further study focused on reducing pneumonia-related fatalities in schizophrenic patients with pneumonia.

Long-term effects of iloperidone on cerebral dopamine receptor subtypes.

The atypical antipsychotic drug iloperidone has high affinity for a wide range of neurotransmitter receptors, including dopaminergic (DA), serotonergic, and adrenergic receptors. We examined the long-term effects of multiple doses of iloperidone on DA D1 , D2 , D3 , and D4 receptor subtypes. Sprague-Dawley adult rats (n = 8/group) received daily intraperitoneal injections of iloperiodone (0.5, 1, or 5 mg/kg) or vehicle for 4 weeks. Receptor autoradiography quantified the levels of DA receptors in medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus (HIP). Four weeks of iloperidone treatment at 5 mg/kg significantly increased D1 receptors in NAc (36%) and CPu (38%). Iloperidone (1.5 and 5 mg/kg) dose-dependently increased D2 receptors in MPC (37 and 47%) and HIP (32 and 40%). Only the high dose of iloperidone (5 mg/kg) increased D2 receptors in NAc (39%) and CPu (38%). Repeated treatment with iloperidone (1.5 and 5 mg/kg) increased D4 receptors in the NAc (39 and 78%), CPu (42 and 83%) and HIP (54 and 72%). The three doses of iloperidone failed to alter D3 receptors in the brain regions examined in this study. These results suggest that iloperidone exerts region- and dose-specific effects on forebrain DA receptor subtypes, which may contribute to its therapeutic benefits in improving the positive and negative symptoms of schizophrenia with minimal extrapyramidal side effects.

Update on the Pharmacological Treatment of Tics with Dopamine-Modulating Agents.

More than 40 years of research and clinical practice have proven the effectiveness of dopamine receptor antagonists in the pharmacological treatment of tics. A blockade of the striatal dopamine-D2 receptors is mainly responsible for their tic-reducing effect. A broad spectrum of dopamine-modulating agents, such as typical and atypical antipsychotics, but also dopamine receptor agonists are used with an immanent discord between experts about which of them should be considered as first choice. The present Review outlines the state of the art on pharmacological treatment of tics with dopamine-modulating agents by giving an systematic overview of studies on their effectiveness and a critical discussion of their specific adverse effects. It is considered as an update of a previous review of our research group published in 2013. The Review closes with a description of the current resulting treatment recommendations including the results of a first published revised survey on European expert's prescription preferences. Based on the enormously growing evidence on its effectiveness and safety, aripiprazole currently seems to be the most promising agent in the pharmacological treatment of tics. Furthermore, benzamides (especially tiapride), which are commonly used in Europe, have proven their excellent effectiveness-tolerability profile over decades in clinical practice and are therefore also highly recommended for the treatment of tics. Nevertheless, pharmacological treatment of tics remains an indiviual choice depending on each patient's own specific needs.

Neutropenia with Multiple Antipsychotics Including Dose Dependent Neutropenia with Lurasidone.

Antipsychotic-induced agranulocytosis is a significant side effect that is known to occur with most of the antipsychotic medications. It usually resolves once the medications are stopped and patients are able to be switched over to another antipsychotic medication. Lurasidone has not been reported to cause leukopenia and neutropenia. This case report is of a patient with a past history of risperidone induced-aganulocytosis developing dose related leukopenia and neutropenia with lurasidone.

[A current view on the history of atypical antipsychotics]. / Sovremennyi vzgliad na istoriiu atipichnykh antipsikhoticheskikh sredstv.

Based on the analysis of the original literature, the author for the first time systemizes the data on the story of atypical antipsychotic drugs. The history of introduction of the first atypical neuroleptics - clozapine and sulpiride, which launched the dichotomic development of psychopharmacology of atypical antipsychotics, is described. Historical facts on the introduction into practice of different sulpiride- and clozapine-like neuroleptics as well as the relationship of their history with the elaboration of dopamine and serotonin hypotheses of mechanisms of action of antipsychotics are presented. The author analyzes the efficacy and tolerability of treatment with different atypical neuroleptics. An importance of evidence-based medicine principles in the history of atypical antipsychotics is described. A significance of the history of some atypical and typical (pericyazine) neuroleptics in the evolution of conceptions on the validity of evidence-based medicine in psychiatry is evaluated. Main stages in the history of typical and atypical antipsychotics are determined.

Differences in Antipsychotic-Related Adverse Events in Adult, Pediatric, and Geriatric Populations.

In recent years, antipsychotic medications have increasingly been used in pediatric and geriatric populations, despite the fact that many of these drugs were approved based on clinical trials in adult patients only. Preliminary studies have shown that the "off-label" use of these drugs in pediatric and geriatric populations may result in adverse events not found in adults. In this study, we utilized the large-scale U.S. Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) database to look at differences in adverse events from antipsychotics among adult, pediatric, and geriatric populations. We performed a systematic analysis of the FDA AERS database using MySQL by standardizing the database using structured terminologies and ontologies. We compared adverse event profiles of atypical versus typical antipsychotic medications among adult (18-65), pediatric (age < 18), and geriatric (> 65) populations. We found statistically significant differences between the number of adverse events in the pediatric versus adult populations with aripiprazole, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and thiothixene, and between the geriatric versus adult populations with aripiprazole, chlorpromazine, clozapine, fluphenazine, haloperidol, paliperidone, promazine, risperidone, thiothixene, and ziprasidone (p < 0.05, with adjustment for multiple comparisons). Furthermore, the particular types of adverse events reported also varied significantly between each population for aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (Chi-square, p < 10-6). Diabetes was the most commonly reported side effect in the adult population, compared to behavioral problems in the pediatric population and neurologic symptoms in the geriatric population. We also found discrepancies between the frequencies of reports in AERS and in the literature. Our analysis of the FDA AERS database shows that there are significant differences in both the numbers and types of adverse events among these age groups and between atypical and typical antipsychotics. It is important for clinicians to be mindful of these differences when prescribing antipsychotics, especially when prescribing medications off-label.

Antipsicóticos de primera y segunda generación en esquizofrenia: eficacia, efectividad y efecto de la dosis utilizada / First and second generation antipsychotics in schizophrenia: efficacy, effectiveness and effect of the dose used

Después de varias décadas de desarrollo de los fármacos antipsicóticos, la esquizofrenia sigue siendo en gran medida una enfermedad crónica con muchos pacientes que experimentan una mala calidad de vida. En este contexto, la aparición de los llamados antipsicóticos de segunda generación fue recibida con gran entusiasmo. Los clínicos esperaban que los nuevos antipsicóticos causaran no solamente menos efectos secundarios motores que los más antiguos, tal como la clorpromazina, sino también que mejoraran los síntomas y la funcionalidad general de los pacientes. Este artículo, de carácter narrativo, revisa cómo inicialmente la evidencia de un gran número de ensayos controlados aleatorios pareció favorecer muchas de estas suposiciones. Esta visión, sin embargo, no era universal, y algunos investigadores destacaron el potencial efecto del diseño de los estudios en los resultados. Un aspecto importante dice relación con la dosis utilizada de antipsicóticos de primera generación, siendo aquellos ensayos que usaron mayores dosis los que apoyaron el uso de antipsicóticos de segunda generación. Esta controversia se resolvió después de la publicación de tres estudios a gran escala, que incluían pacientes menos seleccionados y que enfocaban los resultados a largo plazo en un entorno clínico más "típico", los cuales no encontraron diferencias significativas entre los dos tipos de antipsicóticos. Desde entonces, las discusiones sobre la elección de los antipsicóticos han girado en torno a otros factores tales como los efectos secundarios, más que en su capacidad para controlar los síntomas.(AU)

After several decades of antipsychotic medication development, schizophrenia has largely remained a chronic disease with many patients experiencing poor quality of life. In this context, the appearance of so-called second generation antipsychotics was received with great enthusiasm. Clinicians hoped that the new antipsychotics would not only cause less motor side effects than older ones such as Chlorpromazine, but also improve patients' symptoms and overall functioning. In this narrative article we review how initially the vidence of a large number of randomized controlled trials appeared to favour many of these claims. This view was not universal though, and some researchers highlighted the potential effect of some design aspects of the trials in the results. A particular concern related to the dose of first generation antipsychotic used, with trials favouring second generation frequently using higher doses. This controversy was resolved after the publication of three large studies, including less selected patients and looking at longer-term outcomes in a more "typical" clinical setting, which failed to find significant differences between the two types of antipsychotics. Since then, discussions about the choice of antipsychotic revolve more around other factors such as side-effects than their capacity to control symptom.(AU)

Antipsychotic adjunctive therapy to mood stabilizers and 1-year rehospitalization rates in bipolar disorder: A cohort study.

OBJECTIVES: Antipsychotic adjunctive therapy to mood stabilizers (MSs) may improve relapse prevention; however, only a few naturalistic studies, reflecting more generalizable bipolar disorder (BD) samples, support this notion. We compared the 1-year rehospitalization rates of manic patients with bipolar I disorder (BD-I) who were discharged with MS (lithium or valproate) monotherapy or with adjunctive atypical or typical antipsychotic therapy. METHODS: A total of 201 patients with BD-I who were hospitalized with manic episodes between 2005 and 2013 were retrospectively followed for 1-year rehospitalization rates according to treatment at discharge: MS monotherapy, MS with atypical antipsychotics, and MS with typical antipsychotics. Additionally, time to rehospitalization during the 1-year period after discharge was compared between treatment groups. Multivariable survival analyses adjusted for covariates known to influence rehospitalization were conducted. RESULTS: Rehospitalization rates within 1 year were significantly lower in the MS with atypical antipsychotics group (6.3%) compared to the MS monotherapy group (24.3%, P=.008) and to the MS with typical antipsychotics group (20.6%, P=.02). Time to rehospitalization was significantly longer for the MS with atypical antipsychotics group (345.5 days) compared to the MS monotherapy group (315.1 days, P=.006) and to the MS with typical antipsychotics group (334.1 days, P=.02). The MS with atypical antipsychotics group had a significantly reduced adjusted risk of rehospitalization (hazard ratio=0.17, 95% confidence interval: 0.05-0.61, P=.007) compared to the MS monotherapy group. CONCLUSIONS: Atypical antipsychotic adjunctive therapy to MSs may be more effective than MS monotherapy in preventing rehospitalization during the 1-year period after a BD manic episode.

Trends in the use of antipsychotics in the Israeli inpatient population, 2004-2013.

BACKGROUND: Although serious mental illneses are treated with both typical and atypical antipsychotic grugs, trends in their use in psychiatric inpatient population in Israel are unrecognized. The aim of this study was to detect trends in the use of typical and atypical antipsychotic drugs in the Israeli inpatient psychiatric population throughout the last decade. METHODS: Data regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the electronic records of SAREL, Israel's largest private supplier of drugs to healthcare and medical facilities. The data were converted to defined daily doses (DDD) per 1000 inpatients per day. RESULTS: Usage of the ten atypical antipsychotic agents allocated through Israel's national health care system increased by 73 %, from 128.09 DDD/1000 inpatients/day in 2004 to 221.69 DDD/1000 inpatients/day in 2013. This rise from 2004 to 2013 was largely due to a 1.6-fold increase in the administration of olanzapine (48.31 to 79.57 DDD/1000 inpatients/day), a 4.4-fold increase of quetiapine (9.74 to 43.04 DDD/1000 inpatients/day) and 3.7-fold increase of amisulpride (5.54 to 20.38 DDD/1000 inpatients/day). At the same period, the total utilization of 12 main typical antipsychotics decreased by 15.5 %, from 148.67 DDD/1000 inpatients/day in 2004 to 125.57 DDD/1000 inpatients/day in 2013. Over the entire period, total DDDs of both classes of antipsychotics (typical and atypical) increased by 38 %. CONCLUSIONS: Similar to trends in the treatment of psychiatric outpatients in other countries, there was a substantial increase in the administration of atypical antipsychotic drugs to the Israeli psychiatric inpatient population across the study period. A decrease in the use of typical antipsychotics (substitution), polypharmacy, administration for more indications (supplementation) and the use of larger doses of antipsychotics may account, in part, for this increase. The findings have implications for mental health policy in the context of the Mental Health Care System Reform. Systematic studies on appropriate dosing of antipsychotics and augmentation strategies are warranted.