Does antipsychotic polypharmacy increase the risk for metabolic syndrome?

Correll, Christoph U.; Frederickson, Anne M.; Kane, John M.; Manu, Peter

doi:10.1016/j.schres.2006.08.017

Cited by 225 publications

(183 citation statements)

References 49 publications

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“…The pathogenesis underlying AAP-related MetS is still unknown but some risk factors such as patients older than 50 years, higher body mass index (BMI) at initiation of antipsychotic treatment, BMI increase after initiation of antipsychotic treatment, duration of antipsychotic drug exposure, and those taking clozapine or multiple antipsychotics have been reported. [7][8][9] During the past decade, dramatic advances in molecular biology have led to the modern era of pharmacogenetics, with variability in drug response, which includes both therapeutic and adverse effect, attributed to genetic factors discovered in different populations. The identification of the genetic variants that influence drug-related adverse effect may help pre-treatment selection and development of drugs that are safe for individual patients on the basis of their idiosyncratic pharmacogenetic profile.…”

Section: Introductionmentioning

confidence: 99%

Gene–gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics

Lin

et al. 2010

Pharmacogenomics J

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The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate feedback control of lipid metabolism. In this genetic case-control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics. The study included 456 schizophrenia patients treated with clozapine (n ¼ 171), olanzapine (n ¼ 91) and risperidone (n ¼ 194), for an average of 45.5±27.6 months. The prevalence of MetS among all subjects was 22.8% (104/456). Two single-nucleotide polymorphisms (SNPs) of the INSIG1 gene and seven SNPs of the INSIG2 gene were chosen as haplotypetagging SNPs. In single-marker-based analysis, the INSIG2 rs11123469-C homozygous genotype was found to be more frequent in the patients with MetS than those without MetS (P ¼ 0.001). In addition, haplotype analysis showed that the C-C-C haplotype of rs11123469-rs10185316-rs1559509 of the INSIG2 gene significantly increased the risk of MetS (P ¼ 0.0023). No significant associations were found between polymorphisms of INSIG1 gene and MetS, however, INSIG1 and INSIG2 interactions were found in the significant 3-locus and 4-locus gene-gene interaction models (P ¼ 0.003 and 0.012, respectively). The results suggest that the INSIG2 gene may be associated with MetS in patients treated with AAPs independently or in an interactive manner with INSIG1.

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Section: Introductionmentioning

confidence: 99%

Gene–gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics

Lin

et al. 2010

Pharmacogenomics J

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“…17 Another study found that use of more than one antipsychotic was associated with an increased incidence of metabolic syndrome, although the increased incidence could not be solely related to antipsychotic usage and was also linked to clinical and demographic factors. 18 These studies have all added to the uncertainty regarding the efficacy of antipsychotic polypharmacy, and the BNF states that the 'prescribing of more that one antipsychotic at the same time is not recommended and may constitute a hazard'. 8 A further complication when considering antipsychotic polypharmacy is that the combinations used by clinicians are highly varied.…”

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confidence: 99%

Antipsychotic polypharmacy: review of mechanisms, mortality and management

Langan

Shajahan

2010

Psychiatrist

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Polypharmacy was first described in the psychiatric literature in 1969.1 Studies reported variable rates of concurrent antipsychotic prescription depending on the population considered. A study in Australia, examining people receiving out-patient treatment for schizophrenia, showed a 13% rate of multiple antipsychotic prescription use.2 One Japanese study indicated that the rate of antipsychotic polypharmacy exceeded 90%.3 A recent study in the UK showed an intermediate rate of 30%. 4 Despite its common occurrence, the evidence base behind antipsychotic polypharmacy is widely recognised as limited and its use has been considered both a 'therapeutic option' and a 'dirty little secret'. 5 Routes to polypharmacyWhen considering the prescription of more than one antipsychotic, perceived potential clinical benefit rather than receptor theory often leads to the chosen combination. It is increasingly evident that various non-dopaminergic receptors have an important role in the clinical profile of schizophrenia -with adrenergic, glutamatergic and serotonergic receptors (in particular 5-HT 2A receptors) involved in the pathogenesis of positive and negative symptoms. It is postulated that combined therapy might help to diversify the range of receptors affected by drug treatment and thereby improve symptoms of disease and reduce recurrence rates. 6The National Institute for Health and Clinical Excellence (NICE) has produced algorithms for the use of antipsychotics in schizophrenia. 7 The guidance states that in a first presentation, concurrent antipsychotics should not be prescribed except to cover short change-over periods (i.e. cross-tapering) and recommends that a second antipsychotic could be 'cautiously' trialled in combination with clozapine in patients whose disorder is truly 'treatment resistant', following an inadequate response to adequate trials of initial antipsychotics and also clozapine. It is only in these specific clinical settings that NICE suggests dual antipsychotic prescription should occur. However, antipsychotic polypharmacy prescription may occur in other clinical scenarios. When clinicians aim to switch their patients from one antipsychotic to another by cross-tapering, the switch may never be fully completed as symptoms stabilise or improve. This leads to reluctance on the part of clinician or patient to complete the switch and may postpone the completion of the switch indefinitely, leading to long-term antipsychotic polypharmacy.Clinicians sometimes prescribe antipsychotic doses close to or beyond that defined as maximum by the UK British National Formulary (BNF).8 When this occurs, highdose monitoring protocols are recommended. 9 Good clinical practice suggests that we avoid high-dose prescribing in order to minimise side-effects. For this reason, clinicians may trial more than one antipsychotic at lower doses, leading once again to long-term antipsychotic polypharmacy. However, polypharmacy may in itself unwittingly result in high total dose prescribing. An audit carried out by the Prescrib...

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“…Para determinar si la prescripción de dos o más antipsicóticos estaba asociado a un incremento del riesgo de desarrollar el desorden metabólico, se realizó un estudio en 367 adultos tratados con más de un AP2G y diagnosticados con SMet (40,41). La prevalencia de politerapia antipsicótica alcanzaba el 19,2%, y fue significativamente mayor para aquellos pacientes tratados con clozapina, quetiapina o ziprasidona.…”

Section: ¿Es El Uso De Antipsicóticos De Segunda Generación Un Factorunclassified

Síndrome metabólico y antipsicóticos de segunda generación

Morales¹

2011

Rev. Asoc. Esp. Neuropsiq.

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Does antipsychotic polypharmacy increase the risk for metabolic syndrome?

Cited by 225 publications

References 49 publications

Gene–gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics

Gene–gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics

Antipsychotic polypharmacy: review of mechanisms, mortality and management

Síndrome metabólico y antipsicóticos de segunda generación

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