Pharmacological Treatment Of Schizophrenia Research Articles

Pharmacologic Treatment of Schizophrenia Beyond Dopamine Receptor Blockade—Has Its Time Come Yet?

This Viewpoint describes the need for novel mechanism of action agents for schizophrenia to extend therapeutic options and improve outcomes.

Paraoxonase/Arylesterase Activity of Serum Paraoxonase-1 and Schizophrenia: A Systematic Review and Meta-Analysis.

The presence of a pro-oxidant state in patients with schizophrenia may account for the increased risk of atherosclerosis and cardiovascular disease in this group and supports the potential utility of circulating biomarkers of oxidative stress for risk stratification and management. We investigated this issue by conducting a systematic review and meta-analysis of the association between the circulating concentrations of paraoxonase-1, an antioxidant calcium-dependent high-density lipoprotein (HDL)-associated esterase, with paraoxonase and arylesterase activity in schizophrenia. We searched electronic databases from inception to 31 May 2023 for studies investigating paraoxonase-1 in patients with schizophrenia and healthy controls and assessed the risk of bias and the certainty of evidence (PROSPERO registration number: CRD42023435442). Thirteen studies were identified for analysis. There were no significant between-group differences in paraoxonase (standard mean difference, SMD = 0.12, 95% CI -0.23 to 0.48, p = 0.50; extremely low certainty of evidence) or arylesterase activity (SMD = -0.08, 95% CI -0.39 to 0.23, p = 0.61; very low certainty of evidence). However, in meta-regression and subgroup analysis we observed significant associations between the SMD of paraoxonase and age (p = 0.003), HDL-cholesterol (p = 0.029), and study country (p = 0.04), and the SMD of arylesterase and age (p = 0.007), body mass index (p = 0.012), HDL-cholesterol (p = 0.002), and pharmacological treatment for schizophrenia (p < 0.001). In the absence of overall between-group differences, our systematic review and meta-analysis suggests that alterations in paraoxonase-1 may reflect a pro-oxidant state in specific subgroups of patients with schizophrenia that require further assessment in appropriately designed studies.

Investigating the symptomatic and morphological changes in the brain based on pre and post-treatment: A critical review from clinical to neuroimaging studies on schizophrenia.

Pharmacological treatment for schizophrenia has been a long-standing concern. As a severe neuropsychological illness, schizophrenia is always a challenging disorder to unravel its pathophysiology. Since it exhibits both positive and negative symptoms, such as hallucination and delusion, as well as social isolation and cognitive impairment, following the symptomatic changes is a crucial task for clinicians. Although various pharmacological treatments are available in the form of antipsychotics, however, their actual consequences need to be examined with the observable changes in symptoms as well as the unobservable changes in brain functioning. This study is a first of its kind to critically investigate both clinical and neuroimaging studies to find out the changes being observed in schizophrenia patients after clinical intervention with various antipsychotics. We observed several symptomatic changes being reported in clinical studies incorporating clinical trials of various first-generation and second-generation antipsychotic drugs. Alongside, we encapsulated several neuroimaging studies showing functional and structural changes in the brain of schizophrenia patients triggered by a variety of drugs. The basal ganglia, frontal lobe, temporal lobe, cuneus, and middle occipital gyrus are some of the notable brain regions that were observed to show subtle functional and structural changes. This critical review paper may pave the way for future research into the study of the pathological and morphological changes in the brains of schizophrenia patients as they progress through the course of medicinal therapy.

Persistent delusional disorder: psychopathological remission associated with clozapine-induced epileptic seizures

IntroductionPersistent delusional disorder has some features similar to schizophrenia, although the functionality of patients with this diagnosis is usually higher and is diagnosed at an older age. Although the pharmacological treatment of schizophrenia has been studied extensively, there is not much data on the treatment of persistent delusional disorder. Regarding the use of clozapines specifically in persistent delusional disorders, there are some case reports with encouraging results. Electroconvulsive therapy is not generally used as a treatment for persistent delusional disorder.ObjectivesTo reflect on the relevance of using electronvulsive therapy in the treatment of persistent delusional disorder.MethodsThrough the description of a clinical case in which there was evidence of remission of resistant psychotic symptoms after clozapine-induced epileptic seizures, the authors hypothesize the existence of a direct relationship between the crisis and the resolution of a persistent delusional disorder.ResultsA.F., 78 years old, male. No personal history of psychiatric or medical-surgical illness. Admitted for psychotic decompensation framed in persistent delusional disorder. The patient underwent pharmacological treatment with resistance to three lines of antipsychotics. With the introduction of clozapine 100mg/day, the patient had two epileptic seizures, followed by complete remission of psychotic symptoms.ConclusionsThe clinical case described refers to a patient diagnosed with resistant persistent delusional disorder, with almost immediate resolution of the condition after epileptic seizures induced by clozapine. Taking into account the clinical response in our patient to two spontaneous epileptic seizures, we hypothesize that electroconvulsive therapy may be effective in the treatment of persistent delusional disorder.Disclosure of InterestNone Declared

Comparing the Effects of Adjunct Aspirin and Simvastatin on Psychopathology Among Inpatients With Schizophrenia

Objectives: As a severe mental health condition, schizophrenia presents a chronic and complex clinical manifestation and neuropathology. A large body of literature exists on the pharmacological treatment of schizophrenia. However, evidence on some dimensions of such interventions (e.g., eligible candidates, potential predicting factors of the therapeutic outcomes, safe implementation of these interventions, etc.) are notably scarce. Studies revealed superior influences of adjunct statin therapy over placebo among patients with schizophrenia. The study aimed to investigate the effects of aspirin and simvastatin as adjunctive therapy, compared to placebo on positive and negative symptoms and general psychopathology of patients with schizophrenia. Methods: This is a double-blind, randomized clinical trial. The sample size was estimated to be 15 individuals for each one of the three research groups (n=45). The Positive And Negative Syndrome Scale (PANSS) and the Hamilton Rating Scale For Depression (HAM-D) were employed to collect the study data in the present study. The study patients were recruited from patients admitted to the psychiatric wards of Razi Hospital were identified. The study subjects were randomly divided into two test groups and one control group. All groups were initially treated with risperidone 4 mg daily for 3 weeks. Then, group A received aspirin (325 mg twice daily), whereas group B was prescribed 40 mg/d of simvastatin. However, the control group received a placebo. Psychiatric symptoms were recorded according to the PANSS at the beginning of the study and then at weeks 4 and 8. The results were analyzed using inferential statistics (repeated-measures analysis of covariance) and descriptive statistics in SPSS software v. 20. Results: Of 45 patients, 35(77.78%) were men (Mean±SD age: 45.8±10.5 years), and 10(22.23%) were women (Mean±SD age: 42.3±7.8 years). The mean scores of the positive symptoms of PANSS significantly decreased in the groups treated with aspirin and simvastatin (P=0.006 and P=0.005, respectively). However, no such difference was seen in the controls (P=0.447). Furthermore, the mean scores of the negative symptoms of PANSS significantly decreased in the intervention groups (P&lt;0.001); in addition, no significant differences were seen in the controls after the end of the research program (P=0.18). In addition, the mean scores of the general symptoms of PANSS significantly decreased in the aspirin and simvastatin groups (P&lt;0.001). There was an increase in the same value in the controls, but the increase was not significant (P=0.31). Finally, while the total mean scores of the PANSS increased in the control group (P=0.25), the corresponding scores significantly decreased in the test groups receiving aspirin and simvastatin (P&lt;0.001). Discussion: The present study results indicate that either aspirin or simvastatin can reduce the symptoms of schizophrenia, including general psychopathology, negative symptoms, and positive symptoms in the explored patients. Also, the effectiveness of both drugs was similar, and no significant difference was detected between these medications in reducing the symptoms mentioned above.

How to Improve the Physical Health in Patients with Severe Mental Disorders

Schizophrenia is a severe brain disorder characterised by positive, negative, affective and cognitive symptoms and can be regarded as a disorder of impaired neural plasticity. This lecture focusses on the beneficial role of exercise in schizophrenia and its underlying mechanisms.Apart from the established pharmacological treatments in schizophrenia, aerobic exercise has a profound impact on the plasticity of the brain of both rodents and humans such as inducing the proliferation and differentiation of neural progenitor cells of the hippocampus in mice and rats. Aerobic exercise enhances LTP and leads to a better performance in hippocampus related memory tasks, eventually by increasing metabolic and synaptic plasticity related proteins in the hippocampus. In healthy humans, regular aerobic exercise increases hippocampal volume and seems to diminish processes of ageing like brain atrophy and cognitive decline.Several meta-analyses demonstrate the beneficial effect of exercise on function, positive as well as negative symptoms and brain structure in multi-episode schizophrenia.DisclosureNo significant relationships.

The pharmacological treatment of schizophrenia: How far have we come?

Schizophrenia is a chronic and often severe mental disorder for which antipsychotic drugs are the cornerstone of treatment. Although the essential mechanism of action of these drugs has not changed much since they were first discovered in the 1950s, there have been numerous advances in the context in which these drugs are prescribed, as well as in the considerations for their optimal use. In this review, we summarize five selected issues in which the psychopharmacological treatment of schizophrenia has most evolved. Namely, these are the shift of outcomes of interest from symptoms to recovery, the development of stratified approaches to select the most appropriate treatment for each individual, the recognition of treatment nonadherence as a critical factor determining outcomes, the recommendations for maintenance treatment, and, finally, the promise of new antipsychotic compounds that innovate in their mechanisms of action, improving efficacy/safety profiles. Finally, we discuss how some of these advances have already delivered to improved outcomes in the real world, whereas others have demonstrated efficacy under optimal circumstances yet have not been translated into better outcomes in the community. Thus, the road ahead includes both identifying novel treatments that engage the psychopathology of the illness and improve the efficacy/tolerability profile of currently available agents, as well as developing interventions that mitigate the barriers for the use of novel interventions, some of them already existing, in the real world.

New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review.

The pharmacological treatment of schizophrenia is currently based on the employment of antipsychotic medications showing an antagonism of dopaminergic and serotoninergic inhibitors. 20-40% of patients are drug-resistant or residually symptomatic in the long-term antipsychotic treatment, and new strategies are needed for improving their functional and cognitive impairment. This systematic review has summarized evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, and Google Scholar. The possible role of glutamate and its receptors as targets of the antipsychotic mechanism of action has been described. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. Results show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA- Receptor antagonist) for cognition and psychopathology. The putative antipsychotic effect of cannabidiol on positive symptoms and cognition will also be discussed. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown to induce improvements in cognitive symptoms in schizophrenia, as well as Erythropoietin. Oxytocin has been reported to have an antipsychotic-like effect; moreover, COX-2 inhibitors lead to a reduction in positive symptoms of psychosis, specifically in the first episode of illness. This narrative report suggests a promising role of new agents in the treatment of Schizophrenia; however, more research is needed to approve their clinical employment.

Two in one: simultaneous use of two long-acting antipsychotics in schizophrenia

Objectives. This paper aims to review the literature regarding the possible simultaneous use of two long-acting antipsychotics in the treatment of schizophrenia. Selected literature review. Despite using the appropriate dose in antipsychotic treatment and continuing it for the necessary period, it happens that such treatment may be considered ineffective. In such a case, to supplement the clinical effect of antipsychotics, the addition of a second antipsychotic medication, mood stabiliser, or an antidepressant may be considered. If the inadequate response to the treatment results from poor medication adherence, the use of long-acting antipsychotic is re­commended. Some clinicians, however, try to use two long-acting antipsychotics simultaneously. Conclusions. Sparse available data did not allow us to conclude that the simultaneous use of two long-acting antipsychotic agents significantly improves the outcome of pharmacological treatment of schizophrenia.

Pharmacological Treatment of Schizophrenia: Japanese Expert Consensus.

Introduction Conventional treatment guidelines of schizophrenia do not necessarily provide solutions on clinically important issues. Methods A total of 141 certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology evaluated treatment options regarding 19 clinically relevant situations in the treatment of schizophrenia with a 9-point scale (1=“disagree” and 9=“agree”). Results First-line antipsychotics varied depending on predominant symptoms: risperidone (mean±standard deviation score, 7.9±1.4), olanzapine (7.5±1.6), and aripiprazole (6.9±1.9) were more likely selected for positive symptoms; aripiprazole (7.6±1.6) for negative symptoms; aripiprazole (7.3±1.9), olanzapine (7.2±1.9), and quetiapine (6.9±1.9) for depression and anxiety; and olanzapine (7.9±1.5) and risperidone (7.5±1.5) for excitement and aggression. While only aripiprazole was categorized as a first-line treatment for relapse prevention (7.6±1.0) in patients without noticeable symptoms, aripiprazole (8.0±1.6) and brexpiprazole (6.9±2.3) were categorized as such for social integration. First-line treatments in patients who are vulnerable to extrapyramidal symptoms include quetiapine (7.5±2.0) and aripiprazole (6.9±2.1). Discussion These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.

Identification and Quantification of Antipsychotics in Blood Samples by LC-MS-MS: Case Reports and Data from Three Years of Routine Analysis.

Antipsychotic drugs (AP) are widely prescribed for the treatment of schizophrenia and psychosis. The pharmacological treatment of schizophrenia is often performed with the simultaneous use of two or more antipsychotic agents to achieve the desired control of psychotic symptoms Available AP include both conventional (typical) and new (atypical) antipsychotic medications. Atypical AP, such as quetiapine, now account for the vast majority of AP prescriptions. In forensic toxicology, AP are of considerable interest because of their potential abuse and their involvement in intoxications and suicides. The authors retrospectively examined AP positive cases detected in samples collected during autopsies performed in the Forensic Clinical and Pathology Service of National Institute of Legal Medicine and Forensic Sciences Centre Branch or in other autopsies carried out in the central region of Portugal, between January 2016 and December 2018. A quantitative liquid chromatography-tandem mass spectrometry assay was developed for the simultaneous determination of 16 AP (amisulpride, aripiprazole, chlorpromazine, clozapine, cyamemazine, fluphenazine, haloperidol, levomepromazine, melperone, olanzapine, paliperidone, promethazine, quetiapine, risperidone, sulpiride and ziprasidone) in blood samples of postmortem cases. The Laboratory of Forensic Chemistry and Toxicology received 3,588 requests for toxicological analysis: 1,413 cases were positive for drugs from which 351 (24.8%) cases were positive for AP, 60.1% from male individuals and 39.9% from female. Quetiapine was the most prevalent AP (36.5%) followed by olanzapine (20.8%). During this period, there were 25 postmortem cases with AP blood concentrations above therapeutic range, in which 36% of those are in agreement with the information received (psychological history or acute intoxication suspicion) and the manner of death was suicide. Our results point that antipsychotics are an increasingly prevalent class of drugs. AP must be measured not only in toxic concentrations but also in therapeutic levels in postmortem cases; therefore, it is important to come up with a sensitive method to cover the low therapeutic range in which AP are usually present.

The beliefs of non-psychiatric doctors about the causes, treatments, and prognosis of schizophrenia.

To examine the causal beliefs about schizophrenia of non-psychiatric doctors and whether differential belief in biogenetic vs. psychosocial causes influences doctors' views about treatments and prognosis. Three hundred and five non-psychiatric doctors working in outpatient community centres completed the 'Opinions on mental disorders Questionnaire' after reading a clinical description of people with schizophrenia. The factors most frequently reported as causes of schizophrenia were heredity (65.2%) and use of street drugs (54.1%). Seventy-five per cent of participants endorsed both one or more biological causal factors and one or more psychosocial causal factors. Of the 264 participants who expressed their opinion about the most important cause of schizophrenia, 53.8% indicated a biogenetic cause. Fifty-two per cent of respondents thought it 'completely true' that drugs are useful in schizophrenia, and 33.9% thought it 'completely true' that people with schizophrenia must take drugs all their life. Participants stating that the most important cause was biogenetic more frequently recommended a psychiatrist and less frequently a psychologist. Compared to doctors who indicated a psychosocial cause as the most important one, those who indicated a biogenetic cause were more sceptical about recovery, more confident in the usefulness of drugs, and more convinced of the need of lifelong pharmacological treatments in schizophrenia. These findings suggest the need to provide some doctors with training on the multiple, interacting causes of schizophrenia and the efficacy of the broad range of available treatments. The education of health professionals regarding stigma and its effects on clinical practice is also needed. Viewing schizophrenia as mainly due to a biological cause is associated with greater confidence in the usefulness of drugs, higher belief in the need for lifelong pharmacological treatments, and greater prognostic pessimism. Belief in a biologically oriented model of schizophrenia may lead doctors to underestimate the value of psychologists. Prognostic pessimism among doctors may negatively influence clinical decisions, the information doctors provide to their clients, and clients' own beliefs about their chances of recovery. Belief in the need for lifelong pharmacological treatments in schizophrenia may lead doctors to resist drug withdrawal in case of severe side effects.

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities.

Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine's efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.

Some Remarks for an Agenda Regarding Phenomenologically Oriented Pharmacological Treatment of Schizophrenia

Some Remarks for an Agenda Regarding Phenomenologically Oriented Pharmacological Treatment of Schizophrenia

Pharmacological Treatment for Long-Term Patients with Schizophrenia and Its Effects on Sleep in Daily Clinical Practice: A Pilot Study.

Background: Pharmacological treatment is still the key intervention in the disease management of long-term patients with schizophrenia; however, how it affects sleep and whether gender differences exist remains unclear. Methods: Forty-six long-term outpatients with schizophrenia entered the study. The numbers of antipsychotics, sleep medications, antidepressants, and anxiolytics were analyzed. Moreover, all patients were tested using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Correlation analyses were conducted between the medication used and the scores on the two subjective sleep inventories. Results: A large variability, ranging from 0 to 8, in the total number of psychiatric drugs per person was found between the patients. Despite ongoing pharmacological treatment, the patients scored high on the PSQI, but not on the ESS; this indicates that they report problems with sleep, but not with daytime sleepiness. A significant positive correlation between the use of antipsychotics and the ESS score, but not the PSQI score, was found; moreover, no gender differences were found. Conclusions: A large variability exists in the pharmacological treatment of long-term patients with schizophrenia. To date, patients’ sleep problems have been insufficiently treated, and gender differences have not been adequately accounted for in the pharmacological treatment of schizophrenia. More and larger international clinical studies are warranted to verify the findings of the present preliminary pilot study before any firm conclusions can be drawn and before any changes to the drug treatment of male and female patients with schizophrenia can be recommended.

Activation of phosphoinositide 3-kinase delta by antipsychotic drugs: Preliminary results

Catalytic subunit delta of phosphoinositide 3-kinase, p110δ, encoded by the PIK3CD gene, was recently proposed as a target for pharmacological treatment of schizophrenia. Current antipsychotic drugs were found to decrease the mRNA expression of PIK3CD, but the mechanism of this process is not known. The aim of the study was to elucidate the mechanism by which antipsychotic drugs affect the mRNA expression of PIK3CD. The direct effect of haloperidol, clozapine, olanzapine, quetiapine and amisulpride on p110δ enzymatic activity was tested with a kinase assay, and the results were referenced against data on the mRNA expression of PIK3CD. Haloperidol, clozapine, olanzapine and quetiapine, but not amisulpride, at the concentration of 20-80 μM, were found to significantly increase enzymatic activity of p110δ by up to two times in a dose-dependent manner. Linear regression analysis revealed that more than 40% of the variance in antipsychotic drugs-induced changes in the expression of PIK3CD mRNA was explained only by changes in antipsychotic drug-regulated p110δ enzymatic activity (p = 0.011). Antipsychotic drugs differentially increase the enzymatic activity of p110δ. This effect is associated with that of mRNA expression of the PIK3CD gene. Drug-enzyme interaction may explain the effect of antipsychotic drugs on the expression of PIK3CD mRNA, however, further studies are needed to investigate this hypothesis.

119. The Pharmacologic Treatment of Schizophrenia: How Far Have We Come

119. The Pharmacologic Treatment of Schizophrenia: How Far Have We Come

Severe weight gain after 4-year treatment with aripiprazole in a young man with schizophrenia

Schizophrenia is one of the major problem of the modern psychiatry. Due to its chronic nature, it requires continuous treatment with antipsychotics. Weight gain is one of the major drawbacks associated with the pharmacological treatment of schizophrenia. Aripiprazole is one of the atypical antipsychotics, with relatively good metabolic profile. There are very few published cases of aripiprazole-induced weight gain. We present a case of significant (50 kg) weight gain during 4-year treatment with aripiprazole in a 21-year-old Caucasian man with a diagnosis of paranoid schizophrenia. The mechanism underlying aripiprazole-induced weight gain may be associated with its potent binding to serotonin 5-HT2C receptor. This case confirms how significant is to monitor patients taking antipsychotics.

Pharmacological treatment in schizophrenia

Pharmacological treatment in schizophrenia

Α Markov model for longitudinal studies with incomplete dichotomous outcomes

Missing outcome data constitute a serious threat to the validity and precision of inferences from randomized controlled trials. In this paper, we propose the use of a multistate Markov model for the analysis of incomplete individual patient data for a dichotomous outcome reported over a period of time. The model accounts for patients dropping out of the study and also for patients relapsing. The time of each observation is accounted for, and the model allows the estimation of time‐dependent relative treatment effects. We apply our methods to data from a study comparing the effectiveness of 2 pharmacological treatments for schizophrenia. The model jointly estimates the relative efficacy and the dropout rate and also allows for a wide range of clinically interesting inferences to be made. Assumptions about the missingness mechanism and the unobserved outcomes of patients dropping out can be incorporated into the analysis. The presented method constitutes a viable candidate for analyzing longitudinal, incomplete binary data.