Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

Schizophrenia (SCZ) treatment is essentially limited to the use of typical or atypical antipsychotic drugs, which suppress the main symptoms of this mental disorder. Metabolic syndrome is often reported in patients with SCZ under long-term drug treatment, but little is known about the alteration of lipid metabolism induced by antipsychotic use. In this study, we evaluated the blood serum lipids of a validated animal model for SCZ (Spontaneously Hypertensive Rat, SHR), and a normal control rat strain (Normotensive Wistar Rat, NWR), after long-term treatment (30 days) with typical haloperidol (HAL) or atypical clozapine (CLZ) antipsychotics. Moreover, psychostimulants, amphetamine (AMPH) or lisdexamfetamine (LSDX), were administered to NWR animals aiming to mimic the human first episode of psychosis, and the effects on serum lipids were also evaluated. Discrepancies in lipids between SHR and NWR animals, which included increased total lipids and decreased phospholipids in SHR compared with NWR, were similar to the differences previously reported for SCZ patients relative to healthy controls. Administration of psychostimulants in NWR decreased omega-3, which was also decreased in the first episode of psychosis of SCZ. Moreover, choline glycerophospholipids allowed us to distinguish the effects of CLZ in SHR. Thus, changes in the lipid metabolism in SHR seem to be reversed by the long-term treatment with the atypical antipsychotic CLZ, which was under the same condition described to reverse the SCZ-like endophenotypes of this validated animal model for SCZ. These data open new insights for understanding the potential influence of the treatment with typical or atypical antipsychotics on circulating lipids. This may represent an outcome effect from metabolic pathways that regulate lipids synthesis and breakdown, which may be reflecting a cell lipids dysfunction in SCZ.

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Do antipsychotic drugs lose their efficacy for relapse prevention over time?

The British Journal of Psychiatry ◽

10.1192/bjp.bp.117.201103 ◽

2017 ◽

Vol 211 (3) ◽

pp. 127-129 ◽

Cited By ~ 13

Author(s):

Stefan Leucht ◽

John M. Davis

Keyword(s):

Relapse Prevention ◽

Antipsychotic Drugs ◽

Meta Analysis ◽

Term Treatment ◽

First Episode ◽

Brain Volume Loss ◽

New Findings ◽

Long Term Treatment ◽

Long Term Follow Up

SummaryThere is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

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Lipid metabolism in non-insulin-dependent diabetes: effects of long-term treatment with fructose-supplemented mixed meals

American Journal of Clinical Nutrition ◽

10.1093/ajcn/50.5.1015 ◽

1989 ◽

Vol 50 (5) ◽

pp. 1015-1022 ◽

Cited By ~ 33

Author(s):

A W Thorburn ◽

P A Crapo ◽

W F Beltz ◽

P Wallace ◽

J L Witztum ◽

...

Keyword(s):

Lipid Metabolism ◽

Term Treatment ◽

Insulin Dependent Diabetes ◽

Long Term Treatment ◽

Insulin Dependent

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Administration of ziprasidone for 10 days increases cocaine toxicity in mice

Human & Experimental Toxicology ◽

10.1177/0960327108095471 ◽

2008 ◽

Vol 27 (6) ◽

pp. 499-503 ◽

Cited By ~ 2

Author(s):

K Heard ◽

S Krier ◽

NR Zahniser

Keyword(s):

Atypical Antipsychotic ◽

Term Treatment ◽

Toxic Effects ◽

Neurotransmitter Receptors ◽

Control Group ◽

Long Term Treatment ◽

Significant Difference ◽

Group Survival ◽

Cocaine Toxicity

Long-term treatment with antipsychotic medications alters the regional density of several of the neurotransmitter receptors that mediate cocaine toxicity. However, the effect of either up- or down-regulation of the neurotransmitter receptors on cocaine toxicity is unknown. In this study, we determined if subacute administration of the atypical antipsychotic ziprasidone altered the toxic effects of cocaine in mice. Ziprasidone (4 mg/kg) or placebo was administered to the first two groups of CF-1 mice for 10 days and, then on day 10, an estimated LD50 dose of cocaine (102 mg/kg) was given to these mice. In a third group, in order to produce a ziprasidone withdrawal state, we administered ziprasidone for 10 days, followed by no treatment for 2 days before cocaine administration. There was no significant difference among the three groups in overall survival: 63% in the treatment group, 60% in the withdrawal group, and 80% in the placebo group. Survival time was significantly shorter for the withdrawal group than for the control group. Our study may have been limited by lower than expected serum ziprasidone concentrations and lower than expected lethality from cocaine. However, our findings suggest that administration of an atypical antipsychotic for 10 days may increase the toxic effects of cocaine.

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Renaissance of an animal model for human benign prostatic hyperplasia using mice subject to long-term treatment with estrogen

World Journal of Urology ◽

10.1007/bf00326404 ◽

1986 ◽

Vol 4 (2) ◽

pp. 115-118

Author(s):

G. Bartsch ◽

R. Heilbronner ◽

M. Hurt ◽

H. P. Rohr

Keyword(s):

Animal Model ◽

Benign Prostatic Hyperplasia ◽

Term Treatment ◽

Prostatic Hyperplasia ◽

Long Term Treatment

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Clinical guideline recommendations for antipsychotic long-acting injections

The British Journal of Psychiatry ◽

10.1192/bjp.195.52.s63 ◽

2009 ◽

Vol 195 (S52) ◽

pp. s63-s67 ◽

Cited By ~ 77

Author(s):

John M. Kane ◽

Carlos Garcia-Ribera

Keyword(s):

First Generation ◽

Term Treatment ◽

First Episode ◽

Patterns Of Use ◽

Episode Psychosis ◽

Long Term Treatment ◽

Long Acting ◽

Over 40 Years ◽

Subsequent Relapse

BackgroundLong-acting injections (LAIs) of antipsychotic drugs were developed over 40 years ago in an attempt to improve the long-term treatment of schizophrenia.AimsTo review existing guidelines concerning antipsychotic use generally, and LAIs in particular, and how patients might be identified as potential candidates for LAI treatment.MethodLiterature review.ResultsCurrently several first-generation and one second-generation antipsychotic LAIs are available, with others under development. Although the use of LAIs is widespread around the world, patterns of use vary widely. Important considerations regarding the use of LAIs include the indications for long-term pharmacotherapy in schizophrenia in general, the indications for LAIs, the risks associated with LAIs, the need to update guidelines and the issue of cost.ConclusionsThe use of these injections in first-episode psychosis and treatment-refractory schizophrenia is not currently a focus of recommendations, but should be considered. Long-acting injections remain an underutilised option in many countries despite frequent non-adherence with oral medication and subsequent relapse.

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