Long-acting injectable antipsychotics (LAIs) for maintenance treatment of bipolar and schizoaffective disorders: A systematic review

Abstract

Long-Acting Injectable Antipsychotics (LAIs) are used to overcome non-compliance in psychoses, mainly schizophrenia spectrum disorders. We aimed to summarize available evidence of studies comparing the efficacy of LAIs to placebo or oral medications for Bipolar Disorder JID: NEUPSY [m6+; February 12, 2019;11:45 ] Long-acting injectable antipsychotic treatment; Risperidone long-acting; Paliperidone palmitate long-acting injectable; Aripiprazole monohydrate long-acting injectable (BD) and/or Schizoaffective Disorder (SAD). We searched six databases from inception to 28-March-2018, using the strategy: long-acting antipsychotics AND (bipolar disorder OR schizoaffective disorder OR mania OR manic OR bipolar depression). We included peer-reviewed double-blind comparisons of LAIs for any clinical outcome occurrence in BD, or open mirror studies with same prospective as retrospective assessment periods. We excluded studies reporting on mixed schizophrenia/SAD populations without reporting results separately. The pooled records amounted to 642. After duplicate removal and inclusion/exclusion criteria application, we included 15 studies, 6 double-blind and 9 open, 13 assessing BD and 2 SAD. Depot neuroleptics prevented manic, but not depressive recurrences and may worsen depressive symptoms. Risperidone long-acting injectable was found to be effective in protecting from any mood/manic symptom compared to placebo, but not from depressive recurrences. Add-on or monotherapy paliperidone palmitate in SAD patients protected from psychotic, depressive, and manic symptoms. In patients with BD-I with a manic episode at study enrolment, aripiprazole monohydrate significantly delayed time to recurrence of manic episodes without inducing depressive episodes. LAIs are effective and well-tolerated maintenance treatments for BD and SAD. They showed better efficacy in preventing mania than depression. LAIs may be first-line for BD-I and SAD patients with a manic predominant polarity and with non-adherence problems.

Case Report: Paliperidone Palmitate in the Management of Bipolar I Disorder With Non-compliance

“…In addition, PP1M seems to have some efficacy in the management of psychotic or non-psychotic BD in our study, which is consistent with previously demonstrated efficacy of paliperidone ER and PP1M in patients with current manic or mixed episodes, schizoaffective disorders (15), or psychotic BD (21). However, depressive episode was detected in three cases, suggesting that PP1M may be less effective in the prevention of depression, which is in line with the idea that depot neuroleptics showed better efficacy in preventing mania than depression (27). Combined with the fact that manic symptoms are more associated with non-compliance than depressive symptoms (28), BD with a predominance of manic symptoms may be more suitable to use PP1M.…”

How to treat mania

“…In this line, LAIs ought to be considered and offered as maintenance treatment in patients with poor adherence (82). Aripiprazole monohydrate once-monthly LAI monotherapy has shown to delay time to recurrence of manic episodes without inducing depressive episodes (83).…”

“…Aripiprazole monohydrate once-monthly LAI monotherapy has shown to delay time to recurrence of manic episodes without inducing depressive episodes (83). Risperidone LAI monotherapy (84) or adjunctive therapy (85) was found to be effective in protecting from manic, but not depressive recurrences (82). The studies regarding the use of paliperidone palmitate LAI in the treatment of BD are limited to case-reports (86,87).…”

“…The clinical experience suggests a similar effect to risperidone LAI with less adverse extrapyramidal effects in paliperidone palmitate LAI. In sum, it should be noted that LAIs have shown to prevent manic, but not depressive recurrences and may worsen depressive symptoms; therefore, it should be indicated as first-line treatments for BD patients with a manic PP (82). LAIs can be started during admission for an acute manic episode, thus ensuring adherence during the sensitive period of convalescence.…”

Antipsicóticos inyectables de larga duración

“…Hasta la fecha, no se ha publicado ningún ECA en pacientes con trastorno bipolar 27 , pero sí en pacientes con esquizofrenia. En el tratamiento agudo de la esquizofrenia, el OP (210 mg/2 sem, 300 mg/2 sem y 405 mg/4 sem) demostró ser tan eficaz como su homólogo oral (olanzapina 2,5-15 mg/d) y superior a placebo en remisión clínica y tasas de discontinuación 28 .…”