A PET Study of Dopamine D<sub>2</sub> and Serotonin 5-HT<sub>2</sub> Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone

Mamo, David C.; Kapur, Shitij; Shammi, Chekkera; Papatheodorou, George; Mann, Steve; Therrien, Francois; Remington, Gary

doi:10.1176/appi.ajp.161.5.818

Cited by 179 publications

(98 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with the in vivo data (see above), most of the atypical drugs display higher 5-HT 2A than D 2 occupancy rates when dual-tracer approaches are used (Kapur et al, 1998;Nyberg et al, 1999;Gefvert et al, 2001;Mamo et al, 2004). But although it was suggested that the predominant 5-HT 2A receptor antagonism of atypical drugs protects against EPS (Meltzer, 1999), even atypical substances such as olanzapine or risperidone cause EPS when given in higher doses that lead to D 2 receptor occupancy of more than 80% (Kapur et al, 1998;Nyberg et al, 1999).…”

Section: Antipsychotic Drug Action and Serotonin Receptor Occupancymentioning

confidence: 60%

Serotonin and Schizophrenia

Quednow

Geyer

Halberstadt

2010

Handbook of Behavioral Neuroscience

View full text Add to dashboard Cite

Although the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades. Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin. Serotonin and Schizophrenia AbstractAlthough the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades.Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin.3

show abstract

Section: Antipsychotic Drug Action and Serotonin Receptor Occupancymentioning

confidence: 60%

Serotonin and Schizophrenia

Quednow

Geyer

Halberstadt

2010

Handbook of Behavioral Neuroscience

View full text Add to dashboard Cite

show abstract

“…This dose is similar to the mean modal dose in phase 1 of the CATIE trial . The optimal ziprasidone dose for patients with schizophrenia is thought to be in the range of 120-160 mg/day (Nemeroff et al, 2005;Joyce et al, 2006;Mamo et al, 2004). Further studies are needed to determine whether doses of ziprasidone 4120 mg/day can provide additional efficacy in patients with schizophrenic illness.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Changes in Weight and Plasma Lipids during Maintenance Treatment with Ziprasidone

Weiden

Newcomer

Loebel

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone, three 52-week, open-label extension studies of ziprasidone in outpatients (N ¼ 185) with schizophrenia or schizoaffective disorder successfully completing one of three, 6-week switch studies were carried out. Pre-switch treatment consisted of risperidone (n ¼ 43), olanzapine (n ¼ 71), or conventional antipsychotic agents (n ¼ 71). The maximum length of exposure to ziprasidone was 58 weeks. Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6, 19, 32, 45, and 58. Weight was measured at baseline and during each follow-up visit; height was recorded at baseline for the purpose of body mass index (BMI) calculation. Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global ImpressionFSeverity scale which were obtained at baseline and major follow-up points. Clinically significant sustained improvements in weight, BMI, total cholesterol, and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine. Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters. Mean reductions in weight from baseline to study endpoint were 9.8 kg (po0.001) and 6.9 kg (po0.005) for patients previously treated with olanzapine and risperidone, respectively. These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained, clinically significant improvements in weight and plasma lipids.

show abstract

“…However, dopamine blockade in the striatum (D2 occupancy above 80%) is also considered to be the main cause of extrapyramidal side effects related to acute movement disorders. 1,3,85 A relatively recent hypothesis suggests that moderate dopamine receptor occupancy and fast dissociation could confer antipsychotic activity without causing extrapyramidal side effects. 86,87 Of the five types of dopamine receptors (D 1 -D 5 ), D 2 and D 3 are the most strongly targeted by antipsychotic drugs.…”

Section: Pharmacodynamic Factorsmentioning

confidence: 99%

“…[165][166][167][168] Traditionally, strong targeting of serotonin receptors relative to dopamine receptors (as measured by the 5-HT 2 /D 2 binding ratio) was described as the main characteristic of atypical antipsychotics such as clozapine, risperidone and olanzapine. 85,169 However, it is not clear that this is the reason for their therapeutic efficacy because success has also been achieved using novel antipsychotics with low serotonin affinities. 1,3,4 Of the serotonin (5-HT) receptors, the 5-HT 2A and 5-HT 2C subtypes have been the most extensively studied.…”

Section: Pharmacodynamic Factorsmentioning

confidence: 99%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

View full text Add to dashboard Cite

The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and À141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (À759ÀT/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.

show abstract

A PET Study of Dopamine D₂ and Serotonin 5-HT₂ Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone

Cited by 179 publications

References 46 publications

Serotonin and Schizophrenia

Serotonin and Schizophrenia

Long-Term Changes in Weight and Plasma Lipids during Maintenance Treatment with Ziprasidone

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Contact Info

Product

Resources

About

A PET Study of Dopamine D2 and Serotonin 5-HT2 Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone

Cited by 179 publications

References 46 publications

Serotonin and Schizophrenia

Serotonin and Schizophrenia

Long-Term Changes in Weight and Plasma Lipids during Maintenance Treatment with Ziprasidone

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Contact Info

Product

Resources

About

A PET Study of Dopamine D₂ and Serotonin 5-HT₂ Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone