Role of depot antipsychotic medication in patients requiring long-term antipsychotic treatment for psychotic disorders Q5: In individuals with psychotic disorders (including schizophrenia) who require long term antipsychotic treatment, what is the safety and role of depot antipsychotic medication? Background Long-acting depot antipsychotic medications were developed in the sixties to promote adherence in people with recurrent psychotic disorders, including schizophrenia. Depot antipsychotics simplify the treatment process, are believed to enhance treatment adherence, and eliminate bioavailability problems as well as the risk of overdose. However, there are concerns over adverse effects of depot antipsychotics, including tardive dyskinesia and injection site reactions, lack of flexibility of administration, and low patient acceptance. Population/Intervention(s)/Comparator/Outcome(s) (PICO) Population: adults with psychotic disorders, including schizophrenia Interventions: depot antipsychotic drugs Comparisons: oral Antipsychotics drugs Outcomes: symptoms severity prevention of relapses disability and functioning adverse effects of treatment (movement disorders, weight gain) quality of life mortality treatment adherence 1 Role of depot antipsychotic medication in patients requiring long-term antipsychotic treatment for psychotic disorders users' and families' satisfaction with care List of the systematic reviews identified by the search process INCLUDED IN GRADE TABLES OR FOOTNOTES Adams CE et al (2001). Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. British Journal of Psychiatry, 179:290-9. EXCLUDED IN GRADE TABLES OR FOOTNOTES The following systematic reviews were included in the meta-review by Adams et al, (2001). In addition, NICE update on Schizophrenia (NICE 2009) did not identify any new evidence for the efficacy and safety of depot antipsychotics beyond that included in Cochrane reviews analyzed by Adams et al (2001). A new review on risperidone (Hosalli & Davis 2003) indicate that there is no evidence to suggest that long-acting risperidone has either greater efficacy or greater risk of adverse effects when compared to oral risperidone. Adams CE, David A, Quraishi SN (2004). Depot bromperidol decanoate for schizophrenia. Cochrane Database of Systematic Reviews, (3):CD001719. Mahapatra J et al (1999). Depot flupenthixol decanoate for schizophrenia or other similar psychotic disorders. Cochrane Database of Systematic Reviews, (2):CD001470. David A et al (2005). Depot fluphenazine decanoate and enanthate for schizophrenia. Cochrane Database of Systematic Reviews, (1):CD000307. Abhijnhan A et al (2007). Depot fluspirilene for schizophrenia. Cochrane Database of Systematic Reviews, (1):CD001718. Dieterich M et al (1999). Depot haloperidol decanoate for schizophrenia. Cochrane Database of Systematic Reviews, (1):CD001361. David A, Quraishi SN, Rathbone J (2005). Depot perphenazine decanoate and enanthate for schizophrenia. Cochrane Database of Systematic Reviews, (3):CD001717. Dinesh M, David A, Quraishi SN (2001). Depot pipotiazine palmitate and undecylenate for schizophrenia. Cochrane Database of Systematic Reviews, (3):CD001720. Hosalli P, Davis JM (2003). Depot risperidone for schizophrenia. Cochrane Database of Systematic reviews, (4):CD004161. 2 Role of depot antipsychotic medication in patients requiring long-term antipsychotic treatment for psychotic disorders PICO Table Serial Intervention/Comparison Outcomes Systematic reviews used for Explanation no. GRADE I Depot antipsychotic Symptoms severity Adams et al, 2001 drugs / Oral Antipsychotics drugs Prevention of relapses Adams et al, 2001 Disability and functioning No evidence available Adverse effects of treatment Adams et al, 2001 (movement disorders, weight gain) Quality of life No evidence available Mortality No evidence available Treatment adherence Adams et al, 2001 Total dropout rates Users' and families' satisfaction No evidence available with care Narrative description of the studies that went into the analysis The following systematic reviews are included in the meta-review Systematic review Depot Antipsychotic compared to oral antipsychotic No of RCTs Abhijnhan et al, fluspirilene decanoate 2 2007 David et al, 2005 fluphenazine decanoate and enanthate 6 Mahapatra et al, flupenthixol decanoate 1 1999 Dieterich et al, haloperidol decanoate 2 1999 3 Role of depot antipsychotic medication in patients requiring long-term antipsychotic treatment for psychotic disorders Dinesh et al, 2001 pipotiazine palmitate 3 All 14 RCTs included hospitalized patients with schizophrenia or non affective psychotic disorders randomized to a depot antipsychotic or a oral antipsychotic. Abhijnhan et al, 2007 included two RCTs comparing depot fluspirilene to oral chlorpromazine or trifluoperazine in 64 patients. David et al, 2005 included 6 RCTs (n=419) comparing fluphenazine decanoate with oral neuroleptics. Mahapatra et al, 1999 included just one small low quality study (N=56) of flupenthixol decanoate versus oral penfluridol. Dieterich et al, 1999 included two studies on Haloperidol decanoate versus oral haloperidol (N=22) and versus oral quetiapine (N=35). Dinesh et al, 2001 included 3 studies on depot pipotiazine palmitate versus oral antipsychotics involving 219 patients. GRADE Tables Table 1 Author(s): Lorenzo Tarsitani and Corrado Barbui Date: 2009-07-10 Question: Should Depot antipsychotics vs oral antipsychotics be used for Psychotic disorders including schizophrenia? Settings: Largely in Hospital Bibliography: Adams CE et al (2001). Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. British Journal of Psychiatry, 179:290-9. Summary of findings Quality assessment No of patients Effect Importance Quality No of Other Depot oral Relative Design Limitations Inconsistency Indirectness Imprecision Absolute studies considerations antipsychotics antipsychotics (95% CI) Symptoms severity (lack of improvement) 4 randomised serious1 no serious serious2 serious3 none RR 0.68 (0.54 258 fewer per 1000 (from 113 trials inconsistency 35/65 (53.8%) 50/62 (80.6%) VERY CRITICAL to 0.86) fewer to 371 fewer) LOW Relapses 9 randomised serious1 very serious4 serious2 no serious none RR 0.96 (0.8 to 14 fewer per 1000 (from 72 trials imprecision 146/420 (34.8%) 154/428 (36%) VERY CRITICAL 1.14) fewer to 50 more) LOW 4 Role of depot antipsychotic medication in patients requiring long-term antipsychotic treatment for psychotic disorders Disability and functioning 0 no evidence none 0 fewer per 1000 (from 0 fewer 0/0 (0%) available to 0 fewer) 0/0 (0%) RR 0 (0 to 0) CRITICAL 0 fewer per 1000 (from 0 fewer 0% to 0 fewer) Movement disorders (needing anticholinergics) 7 randomised serious1 serious5 serious2 no serious none RR 1.08 (0.9 to 53 more per 1000 (from 66 trials imprecision 137/197 (69.5%) 134/204 (65.7%) VERY CRITICAL 1.3) fewer to 197 more) LOW Tardive dyskinesia 3 randomised serious1 no serious serious2 serious6 none RR 0.66 (0.33 46 fewer per 1000 (from 92 trials inconsistency 12/133 (9%) 19/139 (13.7%) VERY CRITICAL to 1.3) fewer to 41 more) LOW Quality of life 0 no evidence none 0 fewer per 1000 (from 0 fewer 0/0 (0%) available to 0 fewer) 0/0 (0%) RR 0 (0 to 0) IMPORTANT 0 fewer per 1000 (from 0 fewer 0% to 0 fewer) All-cause mortality 0 no evidence none 0 fewer per 1000 (from 0 fewer 0/0 (0%) available to 0 fewer) 0/0 (0%) RR 0 (0 to 0) IMPORTANT 0 fewer per 1000 (from 0 fewer 0% to 0 fewer) Treatment adherence (total dropouts) 18 randomised serious1 no serious serious2 no serious none RR 1.14 (0.9 to 30 more per 1000 (from 22 106/433 (24.5%) 95/441 (21.5%) IMPORTANT trials inconsistency imprecision 1.45) fewer to 97 more) LOW Users' and families' satisfaction with care 5 Role of depot antipsychotic medication in patients requiring long-term antipsychotic treatment for psychotic disorders 0 no evidence none 0 fewer per 1000 (from 0 fewer 0/0 (0%) available to 0 fewer) 0/0 (0%) RR 0 (0 to 0) IMPORTANT 0 fewer per 1000 (from 0 fewer 0% to 0 fewer) 1 Many studies are old and random allocation, blindness and dropouts were not well described. 2 Patients who are reluctant to take oral antipsychotics are not included in trials. 3 Less than 200 patients were included in the analysis. 4 I squared for fluphenazine decanoate (6 studies) is 76%. 5 Graphical inspection of forrest plot suggests some heterogeneity. 6 CI includes no effect and ranges from appreciable benefit to harm. Additional information that was not GRADEd National Collaborating Centre for Mental Health (NCCMH) 2007: Depot antipsychotics should not be routinely prescribed to pregnant women because there is relatively little information on their safety, and their infants may show extrapyramidal symptoms several months after administration of the depot. These are usually self-limiting. Reference List Abhijnhan A et al (2007). Depot fluspirilene for schizophrenia. Cochrane Database of Systematic Reviews, (1):CD001718. Adams CE, David A, Quraishi SN (2004). Depot bromperidol decanoate for schizophrenia. Cochrane Database of Systematic Reviews, (3):CD001719. Adams CE et al (2001). Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. British Journal of Psychiatry, 179:290-9. David A, Quraishi SN, Rathbone J (2005). Depot perphenazine decanoate and enanthate for schizophrenia. Cochrane Database of Systematic Reviews, (3):CD001717. David A et al (2005). Depot fluphenazine decanoate and enanthate for schizophrenia. Cochrane Database