Long acting injection versus oral risperidone in first-episode schizophrenia: Differential impact on white matter myelination trajectory

Bartzokis, George; Lu, Po H.; Amar, Chetan P.; Raven, Erika P.; DeTore, Nicole R.; Altshuler, Lori L.; Mintz, Jim; Ventura, Joseph; Casaus, Laurie R.; Luo, John; Subotnik, Kenneth L.; Nuechterlein, Keith H.

doi:10.1016/j.schres.2011.06.029

Cited by 89 publications

(67 citation statements)

References 46 publications

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“…A positive answer for benefits on disease progression would provide support to an emerging literature regarding the neuroprotective effects of APs, especially SGAs [Bartzokis et al 2011;Gassó et al 2010].…”

Section: Guidelines and Recommendations For The Treatment Of Schizophmentioning

confidence: 87%

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

Brissos¹,

Ruiz‐Veguilla

Taylor

et al. 2014

Therapeutic Advances in Psychopharmacology

237

200

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Historical background of long-acting injectable antipsychotics Soon after the introduction of antipsychotics (APs) in the 1950s, poor adherence to oral formulations was found to be a critical issue. This led to the development in 1966 of the first long-acting injectable (LAI) AP fluphenazine enanthate, and fluphenazine decanoate some 18 months later, to reduce the incidence of side effects of the former [Johnson, 2009]. Haloperidol decanoate became available in Europe in 1981 and in the USA in 1986 [Knudsen, 1985]. Clinical trial results showed a dramatic reduction in the morbidity of schizophrenia [Gottfries and Green, 1974; Johnson, 2009]. However, the concept of LAIs for schizophrenia was not initially received warmly by the medical profession for fears of increased side effects, lack of efficacy, and the fact this was seen as an attempt by psychiatrists to impose a treatment upon patients without due regard to their feelings or rights [Johnson, 2009] as well as the potential for medicolegal problems [Glazer and Kane, 1992]. However, with subsequent surveys and trials suggesting their benefits [Rifkin et al. 1977; Schooler et al. 1980; Hogarty et al. 1979], LAIs became more widely adopted. The introduction of the oral second-generation APs (SGAs) brought claims of better tolerance and less severe side effects, even though their use may be hindered by metabolic syndrome [Meyer and Stahl, 2009]. They also have potential to prevent or reverse accelerated frontotemporal cortical grey matter decline, and to provide a greater degree of neuroprotection than first generation APs (FGAs) [Keefe et al. 2004; Robinson et al. 2006]. The introduction of SGAs led to a decline in the use of LAI FGAs [Patel et al. 2003; Patel and David, 2005]. However, it soon became clear that atypical characteristics did not bring better adherence rates with oral SGAs. The recent introduction of LAI SGAs allows psychiatrists once

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Section: Guidelines and Recommendations For The Treatment Of Schizophmentioning

confidence: 87%

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

Brissos¹,

Ruiz‐Veguilla

Taylor

et al. 2014

Therapeutic Advances in Psychopharmacology

237

200

View full text Add to dashboard Cite

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“…However, this practice is not evidence based and there are anecdotal reports that LAIs may be of particular value when used early in the course of illness 16, 23, 26, 27, 28, 29, 30. Recently, a few randomized studies have demonstrated the value of using APs early in the course of schizophrenia 31, 32.…”

Section: Discussionmentioning

confidence: 99%

Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent‐onset versus more chronic schizophrenia and a history of criminal justice system involvement

Alphs

Bossie

Mao

et al. 2015

Early Intervention Psych

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AimLong‐acting injectable antipsychotics (APs) are not well studied in recent‐onset schizophrenia. This exploratory analysis of a study designed to reflect real‐world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once‐monthly paliperidone palmitate (PP) and daily oral APs in patients with recent‐onset or chronic illnessMethodsThis randomized, open‐label, event monitoring board–blinded study compared treatment response in subjects with schizophrenia and a history of criminal justice system involvement following treatment with PP or oral APs for 15 months (ClinicalTrials.gov identifier, NCT01157351). Event‐free probabilities were estimated using Kaplan–Meier method; hazard ratios (HRs) were estimated using Cox proportional hazard models. This subgroup analysis analysed data by disease duration (≤5 (recent‐onset) or >5 years (chronic illness) since first psychiatric diagnosis).ResultsSeventy‐seven subjects met the criteria for recent‐onset illness; 365 for chronic illness. HRs (95% CI) for treatment failure for oral APs versus PP were 1.73 (0.87–3.45; P = 0.121) for recent‐onset and 1.37 (1.02–1.85; P = 0.039) for chronic illness. Most common adverse events for PP versus oral APs were injection site pain (recent‐onset, 26% vs. 0%; chronic, 17% vs. 0%), increased weight (14% vs. 6%; 12% vs. 6%), akathisia (14% vs. 9%; 10% vs. 7%), insomnia (12% vs. 17%; 18% vs. 10%) and anxiety (12% vs. 6%; 10% vs. 8%).ConclusionsAlthough neither pre‐planned nor adequately powered, the estimated HRs suggest that the relative advantage of PP over oral APs for reducing the risk for treatment failure may be greater in patients with recent‐onset schizophrenia than in those with more chronic illness.

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“…Improving adherence seems to be particularly important early on in the disease, with greater improvement in clinical outcomes in patients treated with risperidone LAI (RLAI) who were recently diagnosed with schizophrenia than in those with chronic schizophrenia (Olivares et al, 2009). Otherwise, recent studies demonstrated the superiority of RLAI, compared with the oral form, to maintain frontal lobe myelinization, to increase frontal lobe intracortical myelin, and to improve cognitive performance in the first psychotic episode (Bartzokis et al, 2011(Bartzokis et al, , 2012.…”

Section: Reasons For Nonuse Of Depot Medicationmentioning

confidence: 99%

Clinicians’ Attitudes Toward the Use of Long-Acting Injectable Antipsychotics

Samalin¹,

Charpeaud²,

Blanc³

et al. 2013

Journal of Nervous &Amp; Mental Disease

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Depot formulations are not widely used in everyday practice. This study aimed to assess psychiatrists' attitudes toward the use of long-acting injectable (LAI) antipsychotics in schizophrenia. We interviewed 113 French psychiatrists about the factors that influenced their prescription of LAI antipsychotics. Multidimensional and cluster analyses were used to detect correlations. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk for extrapyramidal symptoms; and for secondgeneration LAI, it is the unavailability of the equivalent oral formulation. Four factors incite the psychiatrists to prescribe LAI. Two different clusters of patients can also be identified. Most factors influencing the clinicians' attitudes toward the use of LAI antipsychotics are shared in many countries. Conversely, some attitudes related to organizational aspects, particularly the relevance of health care costs, may vary from one country to another.Key Words: Antipsychotics, long-acting injectable, attitudes, schizophrenia (J Nerv Ment Dis 2013;201: 553Y559) A ccording to systematic reviews, between 40% and 60% of patients with schizophrenia are known to be partially or totally noncompliant to oral antipsychotic medication (Dolder et al., 2002;Valenstein et al., 2004). Poor adherence is associated with higher risk for relapse of schizophrenia and increased health care costs (Patel et al., 2008).However, depot formulations are not widely used in routine practice, with a prescription rate of generally lower than 30% in different countries (Barnes et al., 2009; Patel and David, 2011). However, the use of long-acting injectable (LAI) formulations varies between countries. The prescription rates are higher in France (23.5%;Fourrier et al., 2000) and in the United Kingdom (29%; Barnes et al., 2009) compared with other European countries and with Canada (6.3%; Williams et al., 2006) or the United States (17.6%; West et al., 2008).This discrepancy between countries can be considered to derive from the health care system and from the different attitudes displayed by psychiatrists.Perceived coercion or presumed risks for lower tolerance of depot forms have been identified as factors responsible for this low use (Heres et al., 2006; Patel and David, 2011). More generally, negative attitudes from practitioners toward these forms have been shown to account for part of the low prescription rates of depot antipsychotics (Hamann et al., 2010;Heres et al., 2006Heres et al., , 2008Heres et al., , 2011.The main goal of our study was to assess the attitudes of psychiatrists toward LAI antipsychotics in patients with schizophrenia to understand the reasons for using or not assigning depot treatment.We studied these attitudes in a sample of psychiatrists working in France using the same questionnaire that was used in a population of German psychiatrists (Heres et al., 2006(Heres et al., , 2008. Our results will be discus...

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Long acting injection versus oral risperidone in first-episode schizophrenia: Differential impact on white matter myelination trajectory

Cited by 89 publications

References 46 publications

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent‐onset versus more chronic schizophrenia and a history of criminal justice system involvement

Clinicians’ Attitudes Toward the Use of Long-Acting Injectable Antipsychotics

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