Table.
GRADE Evaluation of interventions for Schizophrenia.
| Important outcomes | Adherence to treatment, Relapse, Symptom severity | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? | |||||||||
| 4 (514) | Symptom severity | Amisulpride versus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of people with schizotypal personality disorder in 1 RCT |
| 5 (781) | Symptom severity | Amisulpride versus olanzapine | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of baseline comparisons |
| at least 4 (at least 624) | Symptom severity | Amisulpride versus risperidone | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for incomplete reporting of data. Consistency point deducted for conflicting results. Directness point deducted for inclusion of a mixed population in 1 RCT |
| 1 (123) | Symptom severity | Amisulpride versus ziprasidone | 4 | –2 | 0 | 0 | 0 | Low | Quality point deducted for sparse data and incomplete reporting of results |
| at least 10 (at least 929) | Symptom severity | Amisulpride versus first-generation antipsychotics | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 13 (1131) | Symptom severity | Chlorpromazine versus placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results, inclusion of open-label trials, and inclusion of RCTs with inadequate blinding and randomisation |
| 1 (164) | Symptom severity | Chlorpromazine versus clozapine | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results |
| at least 5 (at least 241) | Symptom severity | Chlorpromazine versus haloperidol | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and inclusion of trials with inadequate randomisation and blinding |
| 1 (60) | Symptom severity | Chlorpromazine versus risperidone | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results, and unclear blinding |
| 2 (317) | Symptom severity | Clozapine versus haloperidol | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| at least 2 (at least 142) | Symptom severity | Clozapine versus quetiapine | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| at least 4 (at least 503) | Symptom severity | Clozapine versus olanzapine | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data, and inclusion of trials with a high risk of bias |
| 5 (491) | Symptom severity | Clozapine versus risperidone | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for low-dose clozapine compared with high-dose risperidone noted by the authors of the review |
| 1 (146) | Symptom severity | Clozapine versus ziprasidone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (57) | Symptom severity | Clozapine versus zotepine | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| unclear (at least 351) | Symptom severity | Clozapine versus newer atypical antipsychotics (risperidone, zotepine, olanzapine, remoxipride, pooled) | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 17 at most (1603 at most) | Symptom severity | Clozapine versus typical/first-generation antipsychotics | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (22) | Symptom severity | Depot haloperidol decanoate versus standard antipsychotic drugs | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for the study being underpowered to detect clinically important differences |
| 1 (32) | Symptom severity | Depot haloperidol decanoate versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| at least 2 (at least 72) | Symptom severity | Haloperidol versus placebo | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results |
| 5 (1475) | Symptom severity | Haloperidol versus risperidone | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point for conflicting results |
| 5 (684) | Symptom severity | Haloperidol versus olanzapine | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of data. Consistency point deducted for conflicting results |
| 5 (1480) | Symptom severity | Haloperidol versus sertindole | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 3 (299) | Symptom severity | Olanzapine versus placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 2 (794) | Symptom severity | Olanzapine versus aripiprazole | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 3 (at least 715) | Symptom severity | Olanzapine versus paliperidone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 3 (at least 483) | Symptom severity | Olanzapine versus quetiapine | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 5 (at least 810) | Symptom severity | Olanzapine versus risperidone | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| at least 2 (at least 790) | Symptom severity | Olanzapine versus ziprasidone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 24 (4189) | Symptom severity | Olanzapine versus first-generation antipsychotics | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 6 (206) | Symptom severity | Pimozide versus standard antipsychotic drugs | 4 | 0 | 0 | 0 | 0 | High | |
| 2 (812) | Symptom severity | Quetiapine versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (314) | Symptom severity | Quetiapine versus paliperidone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 7 (at least 1264) | Symptom severity | Quetiapine versus risperidone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 3 (908) | Symptom severity | Quetiapine versus ziprasidone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 10 (1926) | Symptom severity | Quetiapine versus first-generation antipsychotics | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (659) | Symptom severity | Risperidone versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (172) | Symptom severity | Risperidone versus sertindole | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 2 (372) | Symptom severity | Risperidone versus aripiprazole | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 2 (at least 500) | Symptom severity | Risperidone versus ziprasidone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (40) | Symptom severity | Risperidone versus zotepine | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (107) | Symptom severity | Risperidone versus flupentixol | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| at least 30 (at least 3455) | Symptom severity | Risperidone versus first-generation antipsychotic drugs | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (514) | Symptom severity | Sulpiride versus first-generation antipsychotic drugs | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (247) | Symptom severity | Ziprasidone versus aripiprazole | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and being underpowered to detect clinically important differences |
| at least 4 (at least 728) | Symptom severity | Ziprasidone versus first-generation antipsychotic drugs | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 15 (at least 1125) | Symptom severity | Zotepine versus first-generation antipsychotic drugs | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 3 (984) | Symptom severity | Aripiprazole versus placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| at least 5 (at least 2409) | Symptom severity | Aripiprazole versus first-generation antipsychotic drugs | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (1305) | Symptom severity | Paliperidone versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of data |
| What are the effects of drug treatments in people with schizophrenia who are resistant to standard antipsychotic drugs? | |||||||||
| 6 (1018) | Symptom severity | Clozapine versus first-generation antipsychotic drugs | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for inclusion of partial responders and for unclear comparator |
| 5 (819) | Relapse | Clozapine versus first-generation antipsychotic drugs | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for inclusion of partial responders and for unclear comparator |
| at least 4 (at least 315) | Symptom severity | Clozapine versus olanzapine, risperidone, and zotepine | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for inclusion of non-treatment-resistant people |
| 4 (395) | Symptom severity | Clozapine versus olanzapine | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (146) | Symptom severity | Clozapine versus ziprasidone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (84) | Symptom severity | Olanzapine versus chlorpromazine | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for inclusion of partial responders and for unclear duration of treatment-resistant illness |
| 1 (306) | Symptom severity | Ziprasidone versus chlorpromazine | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for unclear washout period |
| 1 (300) | Symptom severity | Aripiprazole versus perphenazine | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting. Directness point deducted for no statistical analysis between groups for all outcomes |
| 1 (26) | Symptom severity | Risperidone versus fluphenazine | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for baseline comparisons |
| 1 (25) | Symptom severity | Quetiapine versus fluphenazine | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for the use of baseline comparisons |
| 1 (25) | Symptom severity | Second-generation antipsychotic agents (other than clozapine) versus risperidone | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for the use of baseline comparisons |
| What are the effects of interventions to improve adherence to antipsychotic medication in people with schizophrenia? | |||||||||
| 2 (99) | Adherence to treatment | Behavioural therapy versus usual care | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for uncertain validity of outcome assessment (pill count) |
| 1 (63) | Adherence to treatment | Behavioural therapy versus compliance therapy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 4 (328) | Adherence to treatment | Psychoeducational interventions versus usual care | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for incomplete reporting of data. Consistency point deducted for conflicting results. Directness point deducted for unclear measure of outcome |
| 2 (75) | Adherence to treatment | Psychoeducational interventions versus behavioural therapy | 4 | –2 | –1 | –2 | 0 | Very low | Quality points deducted for sparse data and poor follow-up. Consistency point deducted for conflicting results. Directness points deducted for use of co-intervention (pill box) and uncertain validity of outcome assessment (pill count) |
| 1 (63) | Adherence to treatment | Compliance therapy versus usual care | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 2 (465) | Adherence to treatment | Compliance therapy versus non-specific therapy or health education | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for unclear comparator |
| 7 (at least 369) | Adherence to treatment | Family interventions compared with usual care, single-session family intervention, or psychoeducational intervention | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and inclusion of quasi-randomised RCTs. Directness point deducted for inclusion of people with schizophrenia-related disorders |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.