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Adjunctive antioxidants for schizophrenia versus placebo

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.
Outcome Findings in words Findings in numbers Quality of evidence Global state Improvement, short term. PANSSFollow-up: 6 to 8 weeks Adjunctive antioxidants for schizophrenia may reduce the chance of experiencing the global state outcome but there is no clear difference between people given adjunctive antioxidants for schizophrenia and those receiving placebo. These findings are based on data of low quality. RR 0.77 (0.53 to 1.12) Low Total PANSS scores, short term PANSSFollow-up 6 to 12 weeks On average, people receiving adjunctive antioxidants for schizophrenia scored 6.0 lower than people treated with placebo. There was a clear difference between the groups, but, at present the meaning of this in day-to-day care is unclear. Very low Total BPRS scores, short termBPRSFollow-up 6 to 16 weeks On average, people receiving adjunctive antioxidants for schizophrenia scored 3.2 lower than people treated with placebo. There was a clear difference between the groups, but, at present the meaning of this in day-to-day care is unclear. Low General functioning Short term. GASFollow-up: 6 weeks - 1.11- 8.07- 5.86 Low Medium term. GASFollow-up: 24 weeks - 2.84 2.09- 7.77 High Leaving the study early Short term. Follow-up: 6 to 16 weeks Adjunctive antioxidants for schizophrenia probably causes little or no reduction to the chance of experiencing the treatment outcome, but the difference between people given adjunctive antioxidants for schizophrenia and those receiving placebo is not clear. Data supporting this finding are based on moderate quality evidence. RR 0.73 (0.48 to 1.11) Moderate Adverse effects 1. Serious (any time point) - any serious adverse effect. Various methods Adjunctive antioxidants for schizophrenia may very slightly reduce the chance of experiencing the adverse effect or event outcome but there is no clear difference between people given adjunctive antioxidants for schizophrenia and those receiving placebo. These findings are based on data of low quality. RR 0.65 (0.19 to 2.27) Low

Adjunctive antioxidants for schizophrenia versus placebo

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.
Outcome Findings in words Findings in numbers Quality of evidence Global state Improvement, short term. PANSSFollow-up: 6 to 8 weeks Adjunctive antioxidants for schizophrenia may reduce the chance of experiencing the global state outcome but there is no clear difference between people given adjunctive antioxidants for schizophrenia and those receiving placebo. These findings are based on data of low quality. RR 0.77 (0.53 to 1.12) Low Total PANSS scores, short term PANSSFollow-up 6 to 12 weeks The mean total PANSS scores in the intervention groups was 6.0 lower(10.53 lower to 1.65 lower) Very low Total BPRS scores, short termBPRSFollow-up 6 to 16 weeks The mean total BPRS scores in the intervention groups was 3.2 lower(5.63 lower to 0.78 lower) Low General functioning Short term. GASFollow-up: 6 weeks The mean general functioning - short term in the intervention groups was 1.11 lower(8.07 lower to 5.86 higher) Low Medium term. GASFollow-up: 24 weeks The mean general functioning - medium term in the intervention groups was 2.84 higher(2.09 lower to 7.77 higher) High Leaving the study early Short term. Follow-up: 6 to 16 weeks Adjunctive antioxidants for schizophrenia probably causes little or no reduction to the chance of experiencing the treatment outcome, but the difference between people given adjunctive antioxidants for schizophrenia and those receiving placebo is not clear. Data supporting this finding are based on moderate quality evidence. RR 0.73 (0.48 to 1.11) Moderate Adverse effects 1. Serious (any time point) - any serious adverse effect. Various methods Adjunctive antioxidants for schizophrenia may very slightly reduce the chance of experiencing the adverse effect or event outcome but there is no clear difference between people given adjunctive antioxidants for schizophrenia and those receiving placebo. These findings are based on data of low quality. RR 0.65 (0.19 to 2.27) Low

Acupuncture added to standard dose antipsychotics versus standard dose antipsychotics for schizophrenia

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Not improved, endpoint - medium-term (various similar criteria) Acupuncture added to standard dose antipsychotics may reduce the chance of experiencing the global state outcome when compared with standard dose antipsychotics, but, at present there are only very limited data supporting this finding. RR 0.4 (0.28 to 0.57) Very low Mental state PANSS (not improved, reduced rated < 25%, short-term) Acupuncture added to standard dose antipsychotics may reduce the chance of experiencing the mental state outcome when compared with standard dose antipsychotics, but, at present there are only very limited data supporting this finding. RR 0.65 (0.45 to 0.94) Very low Behaviour Leaving the study early (short-term) Acupuncture added to standard dose antipsychotics may increase the chance of experiencing the behaviour outcome, but, at present it is not possible to be confident about the difference between people given acupuncture added to standard dose antipsychotics and those receiving standard dose antipsychotics and data supporting this finding are very limited. RR 1.33 (0.33 to 5.45) Very low Service outcomes Time in hospital (days) On average, people receiving acupuncture added to standard dose antipsychotics spent 16 days less in hospital than people treated with standard dose antipsychotics. There was no clear difference between the groups. The meaning of this in day-to-day care is unclear. MD 16 lower (19.54 to 12.46 lower ) Moderate Adverse effects Central Nervous System - insomnia (short-term) Acupuncture added to standard dose antipsychotics may slightly reduce the chance of experiencing the adverse effect or event outcome when compared with standard dose antipsychotics. Data are based on low quality evidence. RR 0.30 (0.11 to 0.83) Low Quality of life No clinically important change in quality of life The outcome was not measured/reported in the included studies. Economic outcomes Cost of care The outcome was not measured/reported in the included studies.

Acupuncture added to low dose antipsychotics versus standard dose antipsychotics for schizophrenia

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Relapse (follow-up, long-term) Acupuncture added to low dose antipsychotics may reduce the chance of experiencing the global state outcome when compared with standard dose antipsychotics, but, at present there are only very limited data supporting this finding. RR 0.57 (0.37 to 0.89) Very low Mental state BPRS (not improved, reduced rate < 30%, short-term) Acupuncture added to low dose antipsychotics may reduce the chance of experiencing the mental state outcome, but, at present it is not possible to be confident about the difference between people given acupuncture added to low dose antipsychotics and those receiving standard dose antipsychotics and data supporting this finding are very limited. RR 0.75 (0.18 to 3.07) Very low Behaviour Leaving the study early (short-term) Acupuncture added to low dose antipsychotics may reduce the chance of experiencing the behaviour outcome, but, at present it is not possible to be confident about the difference between people given acupuncture added to low dose antipsychotics and those receiving standard dose antipsychotics and data supporting this finding are very limited. RR 0.81 (0.29 to 2.29) Very low Service outcomes Hospitalisation The outcome was not measured/reported in the included studies. Adverse effects Extrapyramidal symptoms - specific - akathisia (short-term) Acupuncture added to low dose antipsychotics may reduce the chance of experiencing the adverse effect or event outcome when compared with standard dose antipsychotics. Data are based on low quality evidence. RR 0.03 (0 to 0.49) Low Quality of life No clinically important change in quality of life The outcome was not measured/reported in the included studies. Economic outcomes Cost of care The outcome was not measured/reported in the included studies.

Acupuncture versus standard dose antipsychotics for schizophrenia

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Not improved (talk, behaviour and expression still existed as before; the reduction of BPRS < 29%), endpoint (short-term) Acupuncture may reduce the chance of experiencing the global state outcome when compared with standard dose antipsychotics, but, at present there are only very limited data supporting this finding. RR 0.33 (0.19 to 0.59) Very low Mental state BPRS, endpoint (high score = worse, short-term) - traditional acupuncture The mean mental state: BPRS, endpoint (high score = worse, short-term) - traditional acupuncture in the intervention groups was 11.56 lower(16.36 to 6.76 lower) MD 11.56 lower () Very low Behaviour Leaving the study early (short-term) The outcome was not measured/reported in the included studies. Low Service outcomes Hospitalisation The outcome was not measured/reported in the included studies. Adverse effects Extrapyramidal symptoms (short-term) Acupuncture may reduce the chance of experiencing the adverse effect or event outcome when compared with standard dose antipsychotics. Data are based on low quality evidence. RR 0.05 (0 to 0.83) Low Quality of life No clinically important change in quality of life The outcome was not measured/reported in the included studies. Economic outcomes Cost of care The outcome was not measured/reported in the included studies.

Acupuncture added to tcm drug versus tcm drug for schizophrenia

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Not improved (talk, behaviour and expression still existed as before, the reduction of BPRS < 29%), endpoint (short-term) Acupuncture added to tcm drug may slightly reduce the chance of experiencing the global state outcome when compared with tcm drug. Data are based on low quality evidence. RR 0.11 (0.02 to 0.59) Low Mental state No clinically important change in mental state The outcome was not measured/reported in the included studies. Behaviour Leaving the study early (short-term) The outcome was not measured/reported in the included studies. Low Service outcomes Hospitalisation The outcome was not measured/reported in the included studies. Adverse effects Clinically important general adverse effects The outcome was not measured/reported in the included studies. Quality of life No clinically important change in quality of life The outcome was not measured/reported in the included studies. Economic outcomes Cost of care The outcome was not measured/reported in the included studies.

Acupuncture versus tcm drug for schizophrenia

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Not improved, endpoint (short-term) - Not improved (no change in symptoms) - Electroacupuncture Acupuncture may reduce the chance of experiencing the global state outcome when compared with tcm drug. Data are based on low quality evidence. RR 0.52 (0.34 to 0.80) Low Mental state No clinically important change in general mental state The outcome was not measured/reported in the included studies. Behaviour Leaving the study early (short-term) The outcome was not measured/reported in the included studies. Service outcomes Hospitalisation The outcome was not measured/reported in the included studies. Adverse effects Clinically important general adverse effects The outcome was not measured/reported in the included studies. Quality of life No clinically important change in quality of life The outcome was not measured/reported in the included studies. Economic outcomes Cost of care The outcome was not measured/reported in the included studies.

Electric acupuncture convulsive therapy versus electroconvulsive therapy for schizophrenia

Summary
PLEASE PARAPHRASE THE FOLLOWING SUMMARY, IT IS TAKEN DIRECTLY FROM YOUR REVIEW: Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Relapse The outcome was not measured/reported in the included studies. Mental state No clinically important change in general mental state The outcome was not measured/reported in the included studies. Behaviour Leaving the study early (short-term) The outcome was not measured/reported in the included studies. Low Service outcomes Hospitalisation The outcome was not measured/reported in the included studies. Adverse effects Spinal fracture (short-term) Electric acupuncture convulsive therapy may reduce the chance of experiencing the adverse effect or event outcome when compared with electroconvulsive therapy. Data are based on low quality evidence. RR 0.33 (0.14 to 0.81) Low Quality of life No clinically important change in quality of life The outcome was not measured/reported in the included studies. Economic outcomes Cost of care The outcome was not measured/reported in the included studies.

Pimozide for schizophrenia or related psychoses

Pimozide versus any other antipsychotic for schizophrenia or related psychoses

Summary
Enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with effectiveness similar to that of other, more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Relapse Follow-up: average 38 weeks These is no clear difference between pimozide and other antipsychotic drugs. Data supporting this finding are based on moderate quality evidence. RR 0.82 (0.57 to 1.17) Moderate Mental state No improvement Follow-up: 16 weeks There is not a clear difference between pimozide and other antipsychotic drugs for this mental state outcome but data supporting this finding are very limited. RR 1.09 (0.08 to 15.41) Very low Presence of first-rank symptoms Follow-up: 3-12 months Pimozide may reduce the chance of experiencing these problematic symptoms but there is no clear difference between people given pimozide and those receiving any other antipsychotic. These findings are based on data of low quality. RR 0.53 (0.25 to 1.11) Low Adverse effects - Extrapyramidal adverse effects Parkinsonism (rigidity) Follow-up: mean 14 weeks In the short term these is no clear difference between pimozide and other antipsychotic drugs for this adverse effect. These findings are based on data of low quality. There are no data in the longer term. RR 1.25 (0.37 to 4.17) Low Parkinsonism (tremor) Follow-up: mean 29 weeks There is no clear difference between pimozide and other antipsychotic drugs for the adverse effect of causing tremor but these findings are based on data of low quality. RR 1.45 (0.68 to 3.09) Low Missing outcomes The outcome of quality of life was not measured/reported in the included studies.

Haloperidol versus placebo for schizophrenia

Haloperidol versus placebo for schizophrenia

Summary
Haloperidol is an antipsychotic drug but often causes troublesome adverse effects. If there is no other antipsychotic drug, using haloperidol to offset the damaging and potentially dangerous consequences of untreated schizophrenia is justified. Where a choice of drug is available, however, an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias may be more desirable.
Outcome Findings in words Findings in numbers Quality of evidence General outcomes No marked global improvement Follow-up: >6-24 weeks Haloperidol, when compared with placebo, reduces the chance of experiencing 'no improvement'. Data are based on moderate quality evidence. RR 0.67 (0.58 to 0.78) Moderate Not discharged from hospital Follow-up: > 6-24 weeks Haloperidol may reduce the chance of staying in hospital, but, at present it is not possible to be confident about the difference between people receiving haloperidol and people taking placebo. Data supporting this finding are very limited. RR 0.85 (0.47 to 1.52) Very low Relapse Follow-up: < 52 weeks Haloperidol may reduce the chance of relapse, but, at present there is only very limited data supporting this finding. RR 0.69 (0.55 to 0.86) Very low Leaving the study early Follow-up: > 6-24 weeks Haloperidol probably slightly reduces the risk of loss to follow up, but the difference between the two treatments is not quite clear. Data supporting this finding are based on moderate quality evidence. RR 0.54 (0.29 to 1) Moderate Adverse effects - movement disorders Parkinsonism Follow-up: 3 weeks to 3 months Haloperidol substantially increases the risk of movement disorders. Data are based on moderate quality evidence. RR 5.48 (2.68 to 11.22) Moderate Missing outcomes Severe adverse events, such as death, and outcomes such as satisfaction with treatment were not measured/reported in the included studies.

Atypical antipsychotics for psychosis in adolescents

Atypical compared with typical antipsychotics (only short term)

Summary
There is not any convincing evidence suggesting that atypical antipsychotic medications are superior to the older typical medications for the treatment of adolescents with psychosis. However, atypical antipsychotic medications may be more acceptable because fewer symptomatic adverse effects are seen in the short term. Little evidence is available to support the superiority of one atypical antipsychotic medication over another.
Outcome Findings in words Findings in numbers Quality of evidence Global state Worse or no improvement There is no clear difference between the newer atypical antipsychotic drugs and the typical drugs for this global outcome. These findings are based on data of low quality. RR 3.3 (0.41 to 26.81) Low Adverse effects Anticholinergic adverse effects Atypical probably reduces the chance of experiencing dry mouth, constipation, and blurred vision but often doses of the older drugs are such that these type of adverse effects are to be expected. Lower doses of control drug could have offset this risk. Data are based on moderate quality evidence. RR 0.2 (0.05 to 0.8) Moderate Leaving the study because of adverse effects Use of atypical drugs may increase the chance of leaving early because of adverse effects, but the difference between the treatments is not clear. Data supporting this finding are based on moderate quality evidence. RR 3.3 (0.41 to 26.81) Moderate

Quetiapine versus typical antipsychotic medications for schizophrenia

Quetiapine compared to typical antipsychotics for schizophrenia

Summary
Quetiapine may not differ from typical antipsychotics in the treatment of positive symptoms, general psychopathology, and negative symptoms. However, it causes fewer adverse effects in terms of abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain.
Outcome Findings in words Findings in numbers Quality of evidence Global state No clinical significant response There is no clear difference between people given quetiapine and those receiving typical antipsychotic drugs. These findings are based on data of moderate quality. RR 0.96 (0.75 to 1.23 ) Moderate Mental state Average positive symptom score (PANSS) On average, people receiving quetiapine scored higher (worse) than people treated with typical antipsychotic drugs. There was, however, no clear difference between the groups. This finding is based on data of moderate quality. MD 0.02 higher (0.39 lower to 0.43 higher)* Moderate Average negative symptom score (PANSS) On average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. This finding is based on data of moderate quality. MD 0.82 lower (1.59 to 0.04 lower)* Moderate Cognitive function Average score On average, people receiving quetiapine scored higher (better) than people treated with typical antipsychotic drugs. There was no clear difference between the groups. This finding is based on data of very limited quality. MD 1.55 higher (0.62 lower to 3.72 higher)* Very low Leaving the study early For any reason Quetiapine is not clearly more acceptable than typical antipsychotic drugss. These findings are based on data of moderate quality. RR 0.91 (0.81 to 1.01 ) Moderate Adverse effects Extrapyramidal effects Quetiapine may reduce the chance of experiencing these movement disorders. This finding is based on data of moderate quality. RR 0.17 (0.09 to 0.32 ) Moderate Prolactin level Average level (ng/mL) On average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. There was a clear difference between the groups. This finding is based on data of moderate quality. MD 16.20 lower (23.34 to 9.07 lower)* Moderate *The meaning of these findings for day-to-day care is not clear

Risperidone versus other atypical antipsychotics for schizophrenia

Risperidone compared to olanzapine for schizophrenia

Summary
Risperidone seems to produce somewhat more extrapyramidal side effects and clearly more prolactin increase than most other atypical antipsychotics. It may also differ from other compounds in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes it difficult to draw firm conclusions.
Outcome Findings in words Findings in numbers Quality of evidence Global state No clinically significant response Risperidone is not clearly different when compared to olanzapine. Data supporting this finding are based on moderate quality evidence. RR 1.06 (0.99 to 1.13) Moderate Leaving the study early due to any reason Risperidone probably slightly increases the chance of leaving the study early, when compared with olanzapine. Data are based on moderate quality evidence. RR 1.14 (1.07 to 1.21) Moderate Service outcome Number of patients re-hospitalized Follow-up: up to 12 weeks There is no clear difference between risperidone and olanzapine for the outcome of how much hospital/community care is used. These findings are based on data of low quality. RR 1.35 (0.41 to 4.40) Low Mental state Average PANSS score (high = poor) Follow-up: up to 12 weeks On average, people receiving risperidone scored slightly higher (worse) than people treated with olanzapine but there was no clear difference between the groups. The meaning of this in day-to-day care is unclear. This finding is based on data of low quality. MD 0.97 higher (1.1 lower to 3.05 higher) Low Adverse effects At least one adverse effect There was no clear difference between risperidone and olanzapine for this very general adverse effect outcome. These findings are based on data of low quality. RR 0.96 (0.88 to 1.03) Low Quality of life Average QLS scale score (high = poor) Follow-up: over 26 weeks On average, people receiving risperidone scored higher than people treated with olanzapine. There was no clear difference between the groups. The meaning of this in day-to-day care is unclear. This finding is based on data of moderate quality. MD 0.97 higher (1.1 lower to 3.05 higher) Moderate

Valproate for schizophrenia

Valproate in combination with antipsychotics compared to antipsychotics plus placebo or antipsychotics alone for schizophrenia

Summary
There is limited evidence that the augmentation of antipsychotics with valproate may be effective for overall clinical response and also for specific symptoms, especially in terms of excitement and aggression. Evidence was entirely based on open randomized controlled trials. Valproate was associated with a number of adverse events among which sedation and dizziness appeared significantly more frequently than in the control groups.
Outcome Findings in words Findings in numbers Quality of evidence Global outcome Clinically significant response When added to antipsychotic drugs valproate probably increases the chance of improvement. Data are based on moderate quality evidence. RR 1.31 (1.16 to 1.47) Moderate Leaving the study early for any reason Valproate in combination with antipsychotics may slightly reduces the chance of leaving the study early, but the difference between the two treatments is not clear. Data supporting this finding are based on moderate quality evidence. RR 0.76 (0.47 to 1.24) Moderate Use of additional medication for sedation The combination of valproate and antipsychotic drugs may increase the chance of being given additional sedating medication, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited. RR 3.65 (0.11 to 122.31) Very low Mental state Average score (PANSS total, high = poor) On average, people receiving the valproate combination scored lower (better) than people treated with antipsychotics in combination with placebo or antipsychotic drugs alone. There was a clear difference between the groups, but, the meaning of this in day-to-day care is unclear. MD 5.85 lower (7.8 lower to 3.91 lower) Moderate Adverse events Abnormal liver function (blood test changes)* Adding valproate to antipsychotic drug treatment does not clearly cause liver problems. Data supporting this finding are based on moderate quality evidence. RR 1.26 (0.72 to 2.22) Moderate Nausea Adding valproate to antipsychotic drugs probably causes little or no increase to the chance of feeling sick, but the difference between the two treatments is not clear. Data supporting this finding are based on moderate quality evidence. RR 1.22 (0.80 to 1.86) Moderate Missing outcomes and notes Quality of life outcomes were not reported in the included studies. *Increase in alanine transaminase/gamma-glutamyl transpeptidase

Glutamatergic drugs for schizophrenia

Adding glutamatergic drug to antipsychotics compared to the same antipsychotic plus a placebo for schizophrenia

Summary
In general, all glutamatergic drugs appeared to be ineffective in further reducing 'positive symptoms' of the illness when added to the existing antipsychotic treatment. Glycine and D-serine may somewhat improve 'negative symptoms' when added to regular antipsychotic medication, but the results were not fully consistent and data are too few to allow any firm conclusions.
Outcome Findings in words Findings in numbers Quality of evidence Global outcome Relapse (add-on glycine) At present it is not possible to be confident about the effect of adding the glutamatergic drug to standard antipsychotic treatment. Data supporting this finding are very limited. RR 0.39 (0.02 to 8.73) Very low Service outcome Hospital admission (add-on glycine) There is no clarity about the benefits or otherwise of adding a glutamatergic drug to antipsychotics for outcomes about how much hospital/community care is used. Data supporting this finding are based on low quality evidence. RR 2.63 (0.12 to 59.40) Low Mental state No clinically significant improvement (add-on glycine) There is no evidence of clear advantage of using add-on glutamatergic to standard antipsychotic medication. These findings are based on data of low quality. RR 0.92 (0.79 to 1.08) Low Adverse effects Constipation (add-on glycine or D-serine) There is no clarity from very limited data. Additional glutamatergic could cause constipation or help avoid it. Data are very limited. RR 0.61 (0.06 to 6.02) Very low Insomnia (add-on glycine or D-serine) Additional glutamatergic may help or cause insomnia - it is not clear from the very limited data. RR 0.61 (0.13 to 2.84) Very low Missing outcomes Quality of life This outcome was not reported in any studies Depot pipotiazine palmitate and undecylenate for schizophrenia Pipotiazine palmitate compared to oral antipsychotics for schizophrenia Summary Although well-conducted and reported randomized trials are still needed to fully inform practice (no trial data exists reporting hospital and services outcomes, quality of life, satisfaction with care and economics) pipotiazine palmitate is a viable choice for both clinician and person with schizophrenia. Outcome Findings in words Findings in numbers Quality of evidence Global outcomes No important clinical response Follow-up: by 3 week) There is no clear difference between people given pipotiazine palmitate and those receiving oral antipsychotics. These findings are based on data of low quality. RR 2.57 (0.76 to 8.63) Low Leaving the study early Follow-up: up to 5 weeks Pipotiazine palmitate may increase the chance of leaving the study early but the difference difference between people given pipotiazine palmitate and those receiving oral antipsychotics is not clear. These findings are based on data of low quality. RR 3.85 (0.46 to 32.22) Low Mental state Relapse Follow-up: by 18 months) Pipotiazine palmitate has not more - or less - effect on risk of relapse than oral antipsychotics. These findings are based on data of low quality. RR 1.55 (0.76 to 3.18) Low Adverse effects Tardive dyskinesia Oral antipsychotic drugs and pipotiazine palmitate carry similar risks of this problematic movement disorder. These findings are based on data of low quality. RR 1.03 (0.22 to 4.92) Low Dystonia Pipotiazine palmitate may slightly reduce the chance of experiencing this movement disorder but there is no clear difference between people given pipotiazine palmitate and those receiving oral antipsychotics. These findings are based on data of low quality. RR 0.32 (0.04 to 2.89) Low Perazine for schizophrenia Perazine versus other antipsychotic drugs for schizophrenia Summary The number, size and reporting of randomized controlled perazine trials are insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side effects as some atypical antipsychotics but this is based on few comparisons of limited power. Outcome Findings in words Findings in numbers Quality of evidence Global state No better or deterioration) Follow-up: average 4 weeks Perazine is not clearly different then other antipsychotic drugs for this outcome. These findings are based on data of low quality. RR 1.33 (0.36 to 4.97) Low Mental state Average score (BPRS) Follow-up: average 4 weeks The average overall mental state score in the perazine group was lower than for those given other antipsychotic drugs. These findings are based on data of low quality and the meaning of this outcome in day-to-day care remains unclear. MD 0.4 lower (0.74 to 0.06 lower) Low Adverse effects Needing antiparkinson medication Follow-up: average 4 weeks At present it is not possible to be confident about the difference between perazine and other antipsychotic drugs. Data supporting this finding are very limited. RR 1.21 (0.53 to 2.76) Very low Leaving the study early - due to adverse events Follow-up: average 4 weeks There was not a clear difference between perazine and the other antipsychotic drugs for this general outcome reflecting overall adverse event 'load'. These findings are based on data of low quality. RR 0.87 (0.4 to 1.9) Low Overall tolerability Leaving the studies early - any reason Follow-up: 1-3 months Perazine and the comparison antipsychotic drugs were equally tolerated. These findings are based on data of low quality. RR 0.97 (0.68 to 1.38) Low No study reported any data on outcomes such as quality of life or information relating to satisfaction with care. Clotiapine for acute psychotic illnesses Clotiapine compared to other antipsychotic drugs for acute psychotic illnesses Summary There was no evidence to support or refute the use of clotiapine in preference to other antipsychotic drug treatments for management of people with acute psychotic illness. Outcome Findings in words Findings in numbers Quality of evidence General clinical impression No significant improvement There is no clear difference between people given clotiapine and those receiving other antipsychotic drugs for acute psychotic illnesses. These findings are based on data of low quality. RR 0.88 (0.39 to 1.98) Low Not well enough to be discharged Clotiapine is not clearly different to other antipsychotic drugs for this outcome - for people who are acutely unwell. These findings are based on data of low quality. RR 1.04 (0.93 to 1.16) Low Adverse effects Movement disorders - use of antiparkinsonian medication Clotiapine may reduce the use of antiparkinsonian drugs - implying that clotiapine causes less of this effect, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited. RR 0.43 (0.05 to 3.53) Very low Seizure Clotiapine may increase the risk of fits, but, the difference between the two treatments is not clear. This finding is based on data of low quality. RR 3.67 (0.16 to 84.66) Low Satisfaction with care Leaving the study early - any reason There is no clear difference between people given clotiapine and those receiving other antipsychotics for acute psychotic illnesses. These findings are based on data of low quality. RR 2.09 (0.81 to 5.42) Low No study reported any data on outcomes as sedation and information relating to behavioral outcomes such as tranquillisation. Penfluridol for schizophrenia Penfluridol compared to typical antipsychotics (oral) for schizophrenia Summary Although there are shortcomings and gaps in the data, there appears to be enough overall consistency for different outcomes. The effectiveness and adverse effects profile of penfluridol are similar to other typical antipsychotics; both oral and depot. Furthermore, penfluridol is shown to be an adequate treatment option for people with schizophrenia, especially those who do not respond to oral medication on a daily basis and do not adapt well to depot drugs. One of the results favouring penfluridol was a lower drop out rate in medium term when compared to depot medications. It is also an option for people with long-term schizophrenia with residual psychotic symptoms who nevertheless need continuous use of antipsychotic medication. An additional benefit of penfluridol is that it is a low-cost intervention. Outcome Findings in words Findings in numbers Quality of evidence Global state No marked improvement (CGI) Follow-up: 3 to 12 months Penfluridol does not clearly change the chance of experiencing 'no marked improvement' when compared with receiving typical antipsychotic drugs. These findings are based on data of low quality. RR 0.92 (0.68 to 1.24) Low Global state - needing additional antipsychotic Follow-up: less than 3 months There is no clear difference between people given penfluridol and those receiving typical antipsychotics. These findings are based on data of low quality. RR 1.35 (0.90 to 2.01) Low Mental state Average score (BPRS) Follow-up: 3 to 12 months On average, people receiving penfluridol scored higher than people treated with typical antipsychotics (oral) but there was no clear difference between the groups and this finding is based on data of low quality. The meaning of this in day-to-day care is unclear. MD 1.24 higher (4.4 lower to 6.88 higher) Low Adverse events Needing antiparkinsonism medication Follow-up: less than 3 months There is no clear difference between people given penfluridol and those receiving typical antipsychotics (oral). These findings are based on data of low quality. RR 1.09 (0.61 to 1.97) Low Insomnia Follow-up: less than 3 months There is no clear difference between people given penfluridol and those receiving typical antipsychotics (oral). These findings are based on data of low quality. RR 1.07 (0.51 to 2.24) Low No study reported any data on outcomes such as quality of life and information relating to time in services Perphenazine for schizophrenia Perphenazine compared with any antipsychotic drug for schizophrenia Summary Although perphenazine has been used in randomized trials for more than 50 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. All data for the main outcomes were of very low quality evidence. At best it can be said that perphenazine showed similar effects - including adverse events - as several of the other antipsychotic drugs. Outcome Findings in words Findings in numbers Quality of evidence Global state No better or deterioration Follow-up: mean 8 weeks Perphenazine is not clearly different than other drugs for this global outcome and data supporting this finding are very limited. RR 1.04 (0.91 to 1.17) Very low Mental state Mental state - 'no effect' (BPRS score reduction) Follow-up: average 8 weeks At present it is not possible to be confident about the difference between perphenazine and any other antipsychotic drug. Data supporting this finding are very limited. RR 1.24 (0.61 to 2.52) Very low Adverse events Extrapyramidal adverse effects - dystonia Follow-up: average 10 weeks Perphenazine is not clearly different to other antipsychotic drugs and data supporting this finding are very limited. RR 1.36 (0.23 to 8.16) Very low Any serious adverse event Follow-up: average 39 weeks It is also not possible to be confident about the difference between the two treatments. Data supporting this finding are very limited. RR 0.98 (0.68 to 1.41) Very low No study reported any data on outcomes such as death, economic outcomes and information relating to time in services Pharmacological interventions for clozapine-induced hypersalivation Astemizole compared to control for clozapine-induced hypersalivation Summary There is no well-tested treatment for this difficult problem and no data to confidently inform clinical practice. Outcome Findings in words Findings in numbers Quality of evidence Hypersalivation No effect / not cured / not markedly improved Control: propantheline Astemizole probably is probably worse than propantheline - increasing the risk of having 'no effect'. Data are based on moderate quality evidence. RR 2.46 (1.63 to 3.72) Moderate Change in hypersalivation scores (high = good) Control: propantheline On average, people receiving astemizole scored a little lower than people treated with control for clozapine-induced hypersalivation. There was a clear difference between the groups, but, at present the meaning of this in day-to-day care is unclear. MD 0.64 lower (1.14 lower to 0.14 lower) Low Adverse effects Tachycardia Control: doxepin Astemizole may increase the risk of experiencing fast heart rate, but, at present it is not possible to be confident about the difference between the two treatments because data supporting this finding are very limited. RR 5.00 (0.25 to 99.16) Very low Constipation Control: propantheline Astemizole may reduce constipation but there is no clear difference between people given astemizole and those receiving propanthelinecontrol for clozapine-induced hypersalivation. These findings are based on data of low quality. RR 0.60 (0.26 to 1.39) Low Missing outcomes No study reported any data on outcomes such as mental state, quality of life and information relating to time in services Levomepromazine for schizophrenia Levomepromazine versus atypical antipsychotic drugs for schizophrenia Summary Data are few and not high quality and makes it impossible to be confident about on the effects of levomepromazine for schizophrenia. Outcome Findings in words Findings in numbers Quality of evidence Global state Not much improved (CGI) Follow-up: short-term Levomepromazine may increase the risk of not seeing an improvement when compared with atypical antipsychotic drugs, but, at present there are only very limited data supporting this finding. RR 2.33 (1.11 to 4.89) Very low Mental state Any response (<20% decrease PANSS Follow-up: short-term At present it is not possible to be confident about the difference between people given levomepromazine and those receiving atypical antipsychotic drugs. There is very limited data to support this finding. RR 2.5 (0.93 to 6.72) Very low Adverse events Constipation Levomepromazine may slightly reduce the risk of constipation but there is no clear difference between people given levomepromazine and those receiving atypical antipsychotics. These findings are based on data of low quality. RR 0.45 (0.07 to 2.94) Low Dizziness Levomepromazine may increase the chance of experiencing dizziness when compared with atypical antipsychotic drugs. Data are based on low quality evidence. RR 2.59 (1.23 to 5.46) Low Drowsiness There is no clear difference for the outcome of 'drowsiness' between people given levomepromazine and those receiving atypical antipsychotic drugs. These findings are based on data of low quality. RR 0.62 (0.29 to 1.32) Low Dry mouth Dry mouth is no more or less common with levomepromazine compared with those receiving atypical antipsychotic drugs. These findings are based on data of low quality. RR 0.93 (0.45 to 1.95) Low Extrapyramidal symptoms - Needing antiparkinsonian medication Levomepromazine may reduce the risk of movement disorders but, with current data, there is no clear difference between people given levomepromazine and those receiving atypical antipsychotic drugs. These findings are based on data of very limited quality. RR 0.6 (0.16 to 2.2) Very low Pericyazine for schizophrenia Pericyazine versus typical antipsychotic for schizophrenia Summary On the basis of very low quality evidence it is not possible to determine the effects of pericyazine in comparison with antipsychotics such as chlorpromazine or trifluoperazine for the treatment of schizophrenia. There is some evidence, however, that pericyazine may be associated with a higher incidence of extrapyramidal side effects than other antipsychotics. Outcome Findings in words Findings in numbers Quality of evidence Global state Not improved Follow-up: 6-12 weeks Pericyazine may increase the risk of being 'not improved', but, at present it is not possible to be confident about the difference between people receiving pericyazine and those given chlorpromazine or trifluoperazine. Data supporting this finding are very limited. RR 1.24 (0.93 to 1.66) Very low Adverse events Extrapyramidal side effect Follow-up: 6-12 weeks Pericyazine may reduce the chance of experiencing the movement disorder, compared with chlorpromazine or trifluoperazine, but, at present there is only very limited data supporting this finding. RR 0.59 (0.38 to 0.89) Very low Leaving the study early For any reasons Follow-up: 9-12 weeks Pericyazine may reduce the chance of leaving the study early, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited. RR 0.46 (0.11 to 1.9) Very low Missing outcomes No study reported any data on outcomes such as relapse, mental state, cost-effectiveness, and information relating to behavior Depot fluspirilene for schizophrenia Fluspirilene decanoate compared to oral antipsychotics for schizophrenia Summary Participant numbers in each comparison were small so power to identify clear difference is limited. Randomized controlled trial data identified no clear differences between the long-acting injection of fluspirilene and oral medication for outcomes that include adverse effects. Outcome Findings in words Findings in numbers Quality of evidence Global outcome Leaving the study early Follow up: 6 weeks to 5 months Fluspirilene decanoate may increase the risk of leaving the study (reasons not specified), but, the difference is not clear between people given fluspirilene decanoate and those receiving oral antipsychotics. These findings are based on data of low quality. RR 1.18 (0.08 to 16.78) Low Mental state Relapse Follow up: 6 weeks to 5 months Using the depot, long-acting fluspirilene decanoate makes little difference for the outcome of 'relapse' compared with those receiving oral antipsychotics - at least for those willing to be engaged with trials. These findings are based on data of low quality. RR 1.18 (0.08 to 16.78) Low Adverse effects Needing anticholinergic drugs Follow up: 6 weeks to 5 months The depot fluspirilene decanoate does not seem to cause any more movement disorders - for which anticholinergic drugs are used - compared with oral antipsychotics. These findings are based on data of low quality. RR 0.07 (0.00 to 1.07) Low Dizziness Fluspirilene decanoate may reduce the chance of experiencing dizziness compared with the oral antipsycotics. Data are based on low quality evidence. RR 0.59 (0.37 to 0.95) Low Missing outcomes Data on quality of life, and service use (e.g. hospitalization) were not reported in trials.