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Res�menes Epistemonikos

Medwave 2016;16(Suppl 2):e6447 doi: 10.5867/medwave.2016.6447

�Son los antipsic�ticos de dep�sito tan efectivos como los orales en pacientes con un primer episodio psic�tico?

Are depot as effective as oral antipsychotics on first-episode psychosis?

Cristi�n Orus, David Aceituno

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Abstract

Depot antipsychotics have been generally used in patients with chronic schizophrenia with adherence problems to oral therapy. However, it has been suggested they can be a good alternative in earlier stages too. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including two pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether there are differences between depot and oral antipsychotics in first-episode psychosis because the certainty of the available evidence is very low.

Problem

The long-acting injectable (depot) antipsychotics were designed initially for patients with chronic schizophrenia with poor adherence to oral antipsychotics.

However, adherence problems are also common at initial stages, resulting in high rates of relapse, partial symptomatic remission and suicidal risk.

While long-acting injectable antipsychotics are considered safe and effective, doubts about its efficacy compared with oral antipsychotics persist.

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

It is not clear whether there are differences between depot and oral antipsychotics in first-episode psychosis because the certainty of the available evidence is very low.
There are randomized controlled trials not yet included in the existing systematic reviews, so a new review including these would increase the certainty of the evidence.

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We found three systematic reviews [1],[2],[3] including five primary studies [4],[5],[6],[7],[8], of which two correspond to randomized controlled trials [4],[8]. This table and the summary in general are based on the latter.
What types of patients were included	Both studies included adult patients with a recent diagnosis of schizophrenia (DSM IV) [4],[8]. One study included patients with first-episode psychosis only within the last two years prior to the initiation of the study [4]. The other study required all patients had been in contact with antipsychotics for no more than four months before the start of the study [8].
What types of interventions were included	Both studies compared long-acting injectable risperidone to oral risperidone [4],[8]. In one study patients were treated with oral antipsychotics for an average of 7.2 months before randomization, and then for 6 more months [4]. The other study maintained treatment for 12 weeks [8].
What types of outcomes were measured	The reviews addressed the following outcomes: - Acceptance by patients to switch from oral to injectable risperidone. - Non-adherence was defined as the absence of medication during 14 days or more. - Subjective perception of patients regarding adherence by the Rating Scale of Medication Influences (ROMI) [8]. One study measured changes in the volume of white matter in the frontal lobe by using magnetic resonance imaging (MRI) and neurocognitive assessment by CogState computerized cognitive battery [4].

Summary of findings

The information on the effects of depot antipsychotics compared to oral antipsychotics in patients with first-episode psychosis is based on two randomized trials including 65 patients. One study evaluated adherence [8] and one study reported some measure of efficacy [4]. None of the studies reported remission, relapse or rehospitalization.

It is not clear whether there are differences in adherence between depot and oral antipsychotics in first-episode psychosis because the certainty of the available evidence is very low.
No studies were found that evaluated the impact of depot versus oral antipsychotics on remission, relapse or rehospitalization in first-episode psychosis.
It is not clear whether there are differences in efficacy between depot and oral antipsychotics in first-episode psychosis because the certainty of the available evidence is very low.

Other considerations for decision-making

To whom this evidence does and does not apply

This evidence applies to all adult patients with first-episode schizophrenia.

About the outcomes included in this summary

The outcomes presented in this summary are those considered critical for decision making by the authors of this summary.

Balance between benefits and risks, and certainty of the evidence

The certainty of the available evidence is very low so it is not possible to make an adequate risk/benefit balance.

What would patients and their doctors think about this intervention

Despite the high rate of non-adherence in these patients, there is still underuse of depot antipsychotics, particularly in patients who present with a first-episode psychosis. One study [9] observed three factors that influenced that pattern: (a) limited availability of long-acting second generation antipsychotics; (b) preconceived notion of rejection by the patient; and (c) patient's skepticism based on an absence of previous relapses, demonstrating the importance of a patient-centered approach, evaluating this treatment in all patients with first-episode psychosis.
Independent of the therapeutic option chosen, it is important to inform the patient about the existing uncertainty of the evidence.

Resource considerations

The certainty of the evidence is very low, so it is not possible to make an appropriate cost/effectiveness analysis.

Differences between this summary and other sources

The conclusions of our summary are consistent with the conclusions of the individual systematic reviews identified.
Clinical guidelines recommend the use of depot antipsychotics as first line in schizophrenic patients with adherence problems, frequent recurrences, which pose a risk to others, with low insight, for patient preference or when there is a previous positive response. Second generation antipsychotics are also recommended in cognitive deficits and social isolation [10].

Could this evidence change in the future?

The probability that the main findings of this summary change in the future is very high, due to the very low certainty of the evidence so far.
There are at least three randomized controlled trials [11],[12],[13] which have not yet been included in systematic reviews. So a new review including these would increase the certainty of the evidence.

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Oral versus long-acting injectable (depot) antipsychotics for first psychotic episode

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons

Esta obra de Medwave est� bajo una licencia Creative Commons Atribuci�n-NoComercial 3.0 Unported. Esta licencia permite el uso, distribuci�n y reproducci�n del art�culo en cualquier medio, siempre y cuando se otorgue el cr�dito correspondiente al autor del art�culo y al medio en que se publica, en este caso, Medwave.

Edici�n Julio 2022

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