Long-Acting Injectable Antipsychotics: Evidence of Effectiveness and Use

Abstract

Objective: To review the evidence for the role of long-acting injectable (LAI) antipsychotics (APs), especially the second-generation AP (SGA) LAIs, in the treatment of schizophrenia and to discuss the use rates of LAIs in Canada. Method: A search of online medical databases was conducted of the published literature (1995-2012) of the effects of LAIs on the domains of remission, adherence, relapse, and hospitalization. Results obtained from randomized controlled trials (RCTs), systematic reviews, meta-analyses, and large-scale observational studies were included. Expert consensus data were also solicited on LAI use within a Canadian context. Results: While the efficacy of LAIs, compared with placebo, is well established, the evidence from RCTs is equivocal for any specific advantage for SGA LAIs, compared with oral medications, probably owing to challenges in conducting such RCTs. Evidence from methodologically less rigorous studies and from clinical practice suggests some advantages in achieving and maintaining remission, risk of relapse, and hospitalization. The rate of LAI (first-generation AP and SGA) use from published outpatient studies is low at 6.3% in Canada, compared with 15% to 80% worldwide. However, there is a relatively high rate of use in specific early psychosis programs and in conjunction with community treatment orders in Canada. Conclusions: LAIs are at least as effective as oral APs in the treatment of psychotic disorders. The former may have specific advantages for patients who demonstrate covert nonadherence. The underuse of LAIs in Canada needs to be better understood and addressed. W W W Antipsychotiques injectables à action prolongée : données probantes sur l'efficacité et l'utilisation Objectif : Examiner les données probantes sur le rôle des antipsychotiques (AP) injectables à action prolongée (IAP), spécialement ceux de la deuxième génération (APDG) IAP, dans le traitement de la schizophrénie et discuter des taux d'utilisation des IAP au Canada.

The Use of Continuous Treatment Versus Placebo or Intermittent Treatment Strategies in Stabilized Patients with Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with First- and Second-Generation Antipsychotics

“…Current guidelines and recommendations on schizophrenia consider LAAPs as drugs of choice for the treatment of schizophrenia patients with recurrent relapses related to non-adherence with antipsychotic medication [11,65,[152][153][154][155][156]. Recent reviews have never been more vocal about their use in early-episode patients for similar reasons (provided schizophrenia has been diagnosed or clinically highly suspected), as these patients ''have more to lose'' [134,[157][158][159][160][161][162][163][164][165][166][167][168][169][170]. LAAPs may, if presented correctly, be more effective for maintaining medication continuity, preventing relapse, reducing the number and duration of rehospitalizations and, when achieving remission, holding this status [161,166,168,169,[171][172][173][174][175].…”

Aripiprazole Once-Monthly in the Treatment of Acute Psychotic Episodes in Schizophrenia

“…10,11 The efficacy, safety, and tolerability of aripiprazole once-monthly 400 mg (AOM 400) for the treatment of acute exacerbation of psychotic symptoms in adult patients with schizophrenia were demonstrated previously. 12 Aripiprazole once-monthly 400 mg was superior to placebo based on change from baseline to week 10 in Positive and Negative Syndrome Scale (PANSS) total score, as well as PANSS positive and negative subscale scores.…”

“…8,9 The variability observed in patient outcomes can be at least partially attributed to modifiable factors, including nonadherence or partial adherence to treatment. 10 …”

Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate

“…Our data are consistent with an early introduction of LAIs after psychoses onset, be it schizophrenia or schizoaffective disorder, but the same could be apply in the future for bipolar disorder, as ARI was found to delay time to relapse more than placebo (Calabrese et al, ). Since the first solicitations for using LAIs early in the course of schizophrenia (Stip, Abdel‐Baki, Bloom, Grignon, & Roy, ; Zhornitsky & Stip, ), the appropriateness of starting young patients earlier on LAIs is increasingly advanced (Brugnoli et al, ; Karson, Duffy, Eramo, Nylander, & Offord, ; Lytle, McVoy, & Sajatovic, ; Manchanda et al, ; Stevens, Dawson, & Zummo, ).…”