Risperidon (depo) za shizofreniju
Abstract
Background
Risperidone is the first new generation antipsychotic drug made available in a long‐acting injection formulation.
Objectives
To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.
To critically appraise and summarise current evidence on the resource use, cost and cost‐effectiveness of risperidone (depot) for schizophrenia.
Search methods
We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies.
Selection criteria
Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia‐like psychoses.
Data collection and analysis
Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
Main results
Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments:
Risperidone depot versus placebo
Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence).
Risperidone depot versus general oral antipsychotics
The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long‐term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very‐low quality evidence).
Risperidone depot versus oral risperidone
Data for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin‐related adverse events.
Risperidone depot versus oral quetiapine
Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long‐term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin‐related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence).
Risperidone depot versus oral aripiprazole
Relapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin‐related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence).
Risperidone depot versus oral olanzapine
Relapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence).
Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate)
Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin‐related adverse events and glucose‐related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS‐medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence).
Risperidone depot versus typical depot antipsychotics
Outcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long‐term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence).
Authors' conclusions
Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second‐generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.
PICO
Laički sažetak
Liječenje shizofrenije dugodjelujućim oblikom risperidona
Istraživačko pitanje
Risperidon je noviji antipsihotik koji je bio prvi dostupan kao dugodjelujuća injekcija (depot‐injekcija). Ovaj Cochraneov sustavni pregled ispituje kliničke učinke depot‐risperidona na oboljele od shizofrenije.
Dosadašnje spoznaje
Oboljeli od shizofrenije često čuju glasove, vide stvari (haluciniraju) i imaju čudna uvjerenja (paranoje). Mogu također postati povučeni, socijalno izolirani, umorni i bezvoljni. Glavna terapija tih simptoma shizofrenije su antipsihotici. Međutim, ti lijekovi mogu imati ozbiljne nuspojave, kao što su debljanje, nekontrolirano drhtanje, tremor, spazam i umor. Nuspojave su često razlog za prestanak uzimanja lijekova (nepridržavanje terapiji), što može dovesti do ponovnog javljanja simptoma bolesti (relaps).
Obilježja studija
Cochraneov sustavni pregled objavljen je 2015. godine i obuhvaća 12 studija s 5723 ljudi koji su primili depot‐risperidon ili drugi način liječenja (placebo, opći oralni antipsihotici, oralni risperidon, oralni kvetiapin, oralni aripiprazol, oralni olanzapin, atipični/noviji depot‐antipsihotici, stariji depo‐antipsihotici).
Ključni rezultati
Teško je zaključiti iz rezultata ovog Cochraneovog sustavnog pregleda je li depo‐risperidon učinkovitiji u liječenju simptoma shizofrenije od placeba ili drugih oblika liječenja. Za ljude koji su zadovoljni uzimanjem oralnoga oblika lijeka, depo‐risperidon je približno jednak oralnom risperidonu. Ljudi na oralnom risperidonu mogu i dalje imati koristi od liječenja depo‐risperidonom, bez potrebe za uzimanjem tableta. Međutim, u visokim dozama depo‐risperidon može imati ozbiljne nuspojave, navlastito poremećaj kretanja, nekontrolirano drhtanje, spazam i tremor. Depo‐risperidon može biti novi antipsihotik u ljudi koji su prestali uzimati tablete, i tako im pomoći smanjiti relaps uz malo povećanje rizika od nuspojava.
Kvaliteta dokaza
Kvaliteta dokaza uglavnom je niska i u najboljem slučaju osrednja. Potrebno je provesti nova, velika, dugoročna i dobro opisana istraživanja o depo‐risperidonu kao lijeku za oboljele od shizofrenije. Depo‐injekcije se često korite za ljude koji odbijaju liječenje. Takve je ljude teško uključiti u studiju.
Sažetak na engleskom jeziku napisao: Ben Gray, McPin Foundation. http://mcpin.org/