World Psychiatric Association Pharmacopsychiatry Section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia

Tandon, Rajiv; Rh, Belmaker; Gattaz, Wagner F.; López-Ibor, Juan J; Okasha, Ahmed; Singh, Bruce; Stein, Dan J.; Olié, Jean‐Pierre; Fleischhacker, W. W.; Moeller, Hans‐Juergen

doi:10.1016/j.schres.2007.11.033

Cited by 270 publications

(194 citation statements)

References 122 publications

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“…In the light of these findings, we can hypothesize that other variables not investigated in the present study, such as genetic factors, could play a role in SGA response. Further, the higher proportion of depressive symptoms among ER patients confirms that SGAs have a greater efficacy on depression compared with FGAs, a finding that was previously reported by several Authors [34,35].…”

Section: Discussionsupporting

confidence: 80%

Early Antipsychotic Response Predictors in Schizophrenia: A Naturalistic Study

Porcelli¹

2014

JPCPY

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Studies on schizophrenia failed to find predictors of antipsychotic response, early response apart. We therefore hypothesized that early responders (ERs) could be identified by specific clinical characteristics. Two independent samples of schizophrenic patients were analyzed. Further, analyses were repeated merging the two samples (total=171). Factors associated with early response were also analyzed in patients taking first and second generation antipsychotics (FGAs and SGAs). A t test or a wilcoxon test was used to detect significant differences between ERs and early non responders (ENRs). In the investigation sample ERs had a lower illness duration (p=0.02), suffered from more severe positive (p=0.01), general (p=0.01) and hostile avoidance, that is represented by impulsivity, excitement, hostility and uncooperativeness, (p=0.01); these results were substantially confirmed in the replication sample and in the two samples merged. Results obtained in FGAs-treated patients were similar to those observed in the whole sample. In patients taking SGAs, ERs had more severe positive and depressive symptoms, without differences among other factors. In line with previous findings, the most relevant difference between ERs and ENRs was in the age, ERs being with a natural tendency younger (mean age ERs=39.6, ENRs=49.5). Regarding FGAs/SGAs differences, our results suggest that in ENRs treated with FGAs an increase of antipsychotic drug dosage seems to be of scarce benefit. Switching to a SGA might be of more clinical usefulness.

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Section: Discussionsupporting

confidence: 80%

Early Antipsychotic Response Predictors in Schizophrenia: A Naturalistic Study

Porcelli¹

2014

JPCPY

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“…APs also differ in their propensity to induce specific adverse effects; for example, SGAs may be associated with a higher risk of significant metabolic disturbances but a lower risk of TD, compared with FGAs. 4 More importantly, large interindividual differences exist among patients. These differences cannot be predicted clinically but they can have serious consequences leading to repeated medication switches owing to intolerability or lack of efficacy.…”

Section: Limitationsmentioning

confidence: 99%

Pharmacogenetics of Antipsychotics

2014

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Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods:We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses.Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion:First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. W W W La pharmacogénétique des antipsychotiquesObjectif : Au cours des dernières décennies, des efforts croissants ont été déployés dans des études visant à percer l'influence des facteurs génétiques sur le dosage des antipsychotiques (AP), la réponse au traitement, et la survenue d'effets indésirables. Ces études voulaient améliorer les soins cliniques en prédisant le résultat du traitement par AP, et en donnant lieu ainsi à des stratégies de traitement individualisées. Nous présentons les résultats les plus importants obtenus par des études tant de gènes candidats que d'association pangénomique, notamment les facteurs pharmacocinétiques et pharmacodynamiques. Méthodes :Nous avons passé en revue les études sur la pharmacogénétique de la réponse aux AP et des effets indésirables publiées dans PubMed jusqu'au début de 2012. Vu le nombre élevé d'études publiées, notre revue a mis l'accent sur les résultats qui ont été reproduits dans des études indépendantes ou qui sont soutenus par des méta-analyses.

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“…The second-generation antipsychotics are associated with a reduced risk of tardive dyskinesia; however, they still develop particularly in older adults, probably because the mechanisms that improve psychoses overlap with those that result in tardive dyskinesia (Correll et al, 2004;Tarsy et al, 2011). In addition, second-generation drugs are associated with side effects, including weight gain and severe disturbances in lipid and glucose regulation (Tandon et al, 2008;Volavka and Citrome, 2009). Thus, there is a critical need for better treatment options for psychotic disorders or at least to reduce the side effects that develop with their use.…”

Section: Introductionmentioning

confidence: 99%

Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

Bordia

McIntosh²,

Quik

2011

J Pharmacol Exp Ther

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Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidolinduced VCMs by ϳ20% after 5 weeks, with a significant ϳ60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and ␣6␤2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced ␣4␤2* nAChRs in both vehicle and haloperidoltreated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.

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World Psychiatric Association Pharmacopsychiatry Section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia

Cited by 270 publications

References 122 publications

Early Antipsychotic Response Predictors in Schizophrenia: A Naturalistic Study

Early Antipsychotic Response Predictors in Schizophrenia: A Naturalistic Study

Pharmacogenetics of Antipsychotics

Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

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