Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment with topiramate may improve negative symptoms in schizophrenia when added to typical antipsychotic drugs (APDs) but not to clozapine. Both dopaminergic and glutamatergic transmissions in the medial prefrontal cortex (mPFC) are facilitated by atypical, but not typical, APDs, which is thought to improve negative symptoms and cognitive dysfunction in schizophrenia. Our previous results show that topiramate increases prefrontal dopamine (DA) outflow when added to the D(2/3) receptorantagonist raclopride. Here, using intracellular recording in vitro, we investigated the effects of topiramate on glutamatergic neurotransmission in the rat mPFC, both when given alone and in combination with raclopride or clozapine. Neither topiramate nor raclopride alone had any effect on N-methyl-D-aspartate (NMDA)-induced currents in pyramidal cells of the mPFC. However, the combination of topiramate and raclopride facilitated the NMDA-induced currents, and this effect was blocked by the D1 receptor antagonist SCH23390. Topiramate also facilitated the effect of a submaximal, but inhibited the effect of a maximal, concentration of clozapine on these currents. The effect of combined topiramate and a submaximal concentration of clozapine could be blocked by SCH23390. In addition, combined topiramate and raclopride facilitated excitatory postsynaptic potentials. In contrast, topiramate inhibited clozapine's facilitating effect on these potentials. These data may help explain the improvement of negative symptoms when topiramate is used as adjunctive therapy in schizophrenic patients receiving typical APDs, but they may also shed light on the observed deterioration of symptoms when topiramate is added to full dose clozapine.
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PMID:Differential effects of topiramate on prefrontal glutamatergic transmission when combined with raclopride or clozapine. 1958 82

Clozapine represents the treatment of choice for refractory psychosis, although a significant number of individuals demonstrate suboptimal response to it as well, leading to clozapine augmentation strategies. A variety of agents have been investigated in this regard, including mood stabilizers, such as anticonvulsants. Within this group of medications, topiramate is unique in that it is associated with weight loss, making it an attractive option because of clozapine's notable risk for associated metabolic disturbance. A 12-week naturalistic, open study was carried out to examine the potential benefits of topiramate in clozapine-treated individuals with schizophrenia demonstrating a suboptimal clinical response. We were specifically interested in clinical symptoms, changes in metabolic parameters, and tolerability. A total of 20 subjects were enrolled, and 16 completed the study, including 5 individuals with type 2 diabetes. Topiramate augmentation led to a 14% improvement in total Brief Psychiatric Rating Scale scores (P = 0.0003), a 2.5% decrease in body weight (P = 0.015), and was generally well tolerated, paraesthesia being the most common side effect. These findings support topiramate as a viable augmentation strategy in clozapine partial responders, with evidence of both clinical and metabolic benefits.
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PMID:Topiramate augmentation in clozapine-treated patients with schizophrenia: clinical and metabolic effects. 2110 86

Less than half of patients with schizophrenia obtain full response to antipsychotic drugs and, while clozapine represents the treatment of choice for refractory psychosis, a significant number of individuals remain only partially responsive. Despite a need for augmentation in this subpopulation, to date clear choices have not been forthcoming. Because clozapine, along with the majority of second-generation agents (SGAs), are linked to metabolic disturbances, augmentation strategies that do not further exacerbate these side effects are needed. Topiramate, unlike other anticonvulsants used for augmentation purposes, has been associated with weight loss. This article reviews the safety and efficacy of topiramate in treatment-refractory schizophrenia, including effects on metabolic disturbances, which burden this population. While current evidence specifically examining improvements in psychopathology demonstrates small to moderate benefits with topiramate augmentation, a growing body of evidence suggests that topiramate may have beneficial effects on antipsychotic-induced weight gain. We conclude that topiramate's metabolic profile, taken together with a current lack of evidence supporting a particular augmentation strategy, argues for further well-controlled studies examining its potential as an augmentation strategy in schizophrenia.
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PMID:Topiramate in schizophrenia: a review of effects on psychopathology and metabolic parameters. 2330 48

Background. Topiramate (TPM) is a new antiepileptic drug that is used mainly in the treatment of refractory partial epileptic seizures. There are some studies reporting TPM's effectiveness in the treatment and maintenance of some psychiatric illnesses such as acute mania, some other affective disorders, post-traumatic stress disorder and binge-eating disorder. On the other hand, it has been shown that TPM may cause mild to moderate cognitive impairment and is thought to be responsible for a series of neuro-psychiatric signs and symptoms. Some of the available articles that have mentioned the relationship of psychotic symptoms and topiramate usage are discussed. Objective. The present paper aims to discuss a case of psychotic exacerbation purported to occur after TPM administration and to review specifically the literature on TPM's potential for inducing psychotic symptoms. The patient presented here is thought to be an undiagnosed schizophrenia patient until his admission to our clinic (Department of Psychiatry, Gazi University Medical School) with TPM-exacerbated psychotic symptoms. Conclusions. The current findings are still subject to controversy because of the presence of both individual case reports and case series on the association between appearance of psychotic symptoms and TPM usage.
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PMID:Topiramate-induced psychotic exacerbation: case report and review of literature. 2494 Jul 28

Patients with schizophrenia have increased prevalence rates for many cardiometabolic risk factors; the prevalence and severity of these risks increase after the institution of antipsychotic medication. Nearly 2 dozen different pharmacologic interventions have been trialed to prevent or attenuate antipsychotic-related cardiometabolic changes. Metformin (usually 1,000-1,500 mg/d) has emerged as the best-studied intervention; in short- and intermediate-duration randomized controlled trials, it has been shown to bring about improvements in weight and other anthropometric indices, in fasting sugar and other glycemic control indices, and in total cholesterol and other lipid metabolism indices. Topiramate and aripiprazole are other possible interventions with support in literature; besides improving metabolic outcomes, these drugs may improve indices of psychopathology, as well. Encouraging though the findings are, there are many unanswered questions that require attention in future research.
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PMID:Cardiometabolic Risks in Schizophrenia and Directions for Intervention, 3: Psychopharmacological Interventions. 2778 Mar 28

This study aimed to perform a comprehensive meta-analysis of topiramate-augmentation therapy in patients with schizophrenia receiving antipsychotic agents. Data published up to June 20, 2016 were obtained from the PubMed, PsycINFO, and Cochrane Library databases. Twelve randomized controlled trials comparing topiramate to placebo or antipsychotic only were included (n=676 patients). The primary outcome was change in overall symptoms. Relative risk (RR) and standardized mean difference (SMD), along with 95% confidence intervals, were calculated using random effects model for each outcome. Topiramate-augmentation therapy was superior to the control for decreasing overall symptoms (SMD -0.55, 95% confidence interval -0.86 to -0.24; P=0.001; I2=55%, eight comparisons, n=380), positive symptoms (SMD -0.4), negative symptoms (SMD -0.47), and Positive and Negative Syndrome Scale general subscale scores (SMD -0.67). Furthermore, topiramate-augmentation therapy decreased weight (SMD -0.69) and body mass index (SMD -0.95) compared with the control. Topiramate was similar to the control with respect to discontinuation due to all causes (RR 1.19), inefficacy (RR 1.71), and adverse events (RR 1.09). Topiramate was associated with higher incidence of paresthesia (RR 2.67) and attention difficulty (RR 8.97) compared with the control. Our results seemed to suggest that topiramate-augmentation therapy improves the psychopathology of schizophrenia with good tolerability and has the additional advantage of weight maintenance. However, because there were some limitations (numbers of studies and patients included in the meta-analysis were small, some studies used completer analysis, Chinese studies were included in the meta-analysis, and studies that had a risk of bias were included in the meta-analysis) in this study, we cannot apply the results of this study in daily clinical practice.
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PMID:Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials. 2800 59

Topiramate has been used increasingly in the management of psychiatric conditions. Clinical trials demonstrated that topiramate augmentation was effective in controlling negative symptoms in schizophrenia. This case report presents a case of a 38-year-old man with schizophrenia who achieved full negative symptom remission upon the adjunctive use of topiramate. However, the remarkable finding of this case is the concomitant decrease in the level of prolactin when topiramate (50 mg/day) was started and the rebound after discontinuation of topiramate. Previous studies stated that topiramate could prevent antipsychotic-induced weight gain and adverse metabolic effects. To the authors' knowledge, no study has reported that topiramate augmentation could be a treatment strategy for antipsychotic-induced hyperprolactinemia. This finding could be verified by well-designed clinical trials.
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PMID:Topiramate add-on treatment associated with normalization of prolactin levels in a patient with schizophrenia. 2857 86

We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 meta-analyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=-0.98) and exercise interventions (SMD=-0.96), followed by psychoeducation (SMD=-0.77), aripiprazole augmentation (SMD=-0.73), topiramate (SMD=-0.72), d-fenfluramine (SMD=-0.54) and metformin (SMD=-0.53). Regarding waist circumference reduction, aripiprazole augmentation (SMD=-1.10) and topiramate (SMD=-0.69) demonstrated the best evidence, followed by dietary interventions (SMD=-0.39). Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=-0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=-0.71) and metformin (SMD=-0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=-0.39), dietary interventions (SMD=-0.37) and aripiprazole augmentation (SMD=-0.34), whereas insulin resistance improved the most with metformin (SMD=-0.75) and rosiglitazone (SMD=-0.44). Topiramate had the greatest efficacy for triglycerides (SMD=-0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=-0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=-0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=-0.35 to -0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.
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PMID:The impact of pharmacological and non-pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta-review of meta-analyses of randomized controlled trials. 3060 Jun 26

Objective: Based on a substantial literature, olanzapine appears to be one of the most efficacious antipsychotics marketed in the United States, with only clozapine clearly more advantageous. However, olanzapine is marred by an equally substantial literature demonstrating a metabolic burden of olanzapine, particularly for weight gain. With the publication of successful strategies to limit olanzapine induced weight gain, a reassessment of the clinical utility of olanzapine appears warranted. The purpose of this paper is to review recent evidence for olanzapine, highlighting use in both schizophrenia and other conditions, safety and supporting the use of olanzapine above 20 mg/day, focusing on studies published since our previous reviews in 2008 and 2009.Data Sources: The US National Library of Medicine's PubMed resource (https://www.ncbi.nlm.nih.gov/pubmed/) was searched using the text word 'olanzapine' for all English-language articles published between 2008 to July 2019, inclusive with a specific focus on double-blind randomized controlled trials and meta-analyses. In addition, we examined the review articles for other reports of interest that may have been missed by our initial search.Data Extraction: The studies were evaluated based on efficacy and safety data.Results: Use of olanzapine may be decreasing but remains common overall. Evidence continues to support both the relative efficacy advantage and weight gain/metabolic disadvantages of olanzapine in schizophrenia, and recent research supports olanzapine's use in treating anorexia nervosa and chemotherapy-induced nausea. The evidence for high dose olanzapine dosages >20 mg remains limited. Non-pharmacological options, such as dietary counseling and exercise, appear to be efficacious in addressing antipsychotic-induced weight gain. Topiramate, metformin and possibly the olanzapine-samidorphan combination also appear helpful.Conclusions: Olanzapine remains a useful antipsychotic, but requires with careful monitoring. Further research is needed to compare the different options available to mitigate olanzapine-induced weight gain and to evaluate potential synergism between pharmacological and non-pharmacological treatments.
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PMID:New discoveries for an old drug: a review of recent olanzapine research. 3181 11


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