Tratamiento complementario con zonisamida para la epilepsia focal
Appendices
Appendix 1. CRS Web search strategy
1. (Zonisamid* OR Exceglan OR Excegram OR Excegran OR ZNS OR Zonegran):AB,KW,KY,MC,MH,TI AND CENTRAL:TARGET
2. MESH DESCRIPTOR Epilepsies, Partial EXPLODE ALL AND CENTRAL:TARGET
3. ((partial or focal) and (seizure* or epilep*)):AB,KW,KY,MC,MH,TI AND CENTRAL:TARGET
4. #2 OR #3 AND CENTRAL:TARGET
5. #1 AND #4
6. (monotherap* NOT (adjunct* OR "add‐on" OR "add on" OR adjuvant* OR combination* OR polytherap*)):TI AND CENTRAL:TARGET
7. #5 NOT #6
8. >04/09/2017:CRSCREATED AND CENTRAL:TARGET
9. #7 AND #8
Zonisamide MeSH term not yet available in CRS Web
Appendix 2. MEDLINE search strategy
The following search strategy is based on the Cochrane Highly Sensitive Search Strategy for identifying randomised trials published in Lefebvre 2011.
1. exp Zonisamide/
2. (Zonisamid* or Exceglan or Excegram or Excegran or ZNS or Zonegran).tw.
3. 1 or 2
4. exp Epilepsies, Partial/
5. ((partial or focal) and (seizure$ or epilep$)).tw.
6. 4 or 5
7. 3 and 6
8. (monotherap$ not (adjunct$ or "add‐on" or "add on" or adjuvant$ or combination$ or polytherap$)).ti.
9. 7 not 8
10. (randomised controlled trial or controlled clinical trial or pragmatic clinical trial).pt. or (randomi?ed or placebo or randomly).ab.
11. clinical trials as topic.sh.
12. trial.ti.
13. 10 or 11 or 12
14. exp animals/ not humans.sh.
15. 13 not 14
16. 9 and 15
17. limit 16 to ed=20170904‐20190917
18. 16 not (1$ or 2$).ed.
19. 18 and (2017$ or 2018$ or 2019$).dt.
20. 17 or 19
21. remove duplicates from 20
Appendix 3. SCOPUS search strategy
((TITLE‐ABS‐KEY(Zonisamide or Zonegran or Excegran)) and not (TITLE‐ABS‐KEY(monotherap* AND NOT (adjunct* or "add‐on" or "add on")))) and (((TITLE‐ABS‐KEY(epilep* OR "infantile spasm" OR seizure OR convuls* OR (syndrome W/2 (aicardi OR angelman OR doose OR dravet OR janz OR jeavons OR "landau kleffner" OR "lennox gastaut" OR ohtahara OR panayiotopoulos OR rasmussen OR rett OR "sturge weber" OR tassinari OR "unverricht lundborg" OR west)) OR "ring chromosome 20" OR "R20" OR "myoclonic encephalopathy" OR "pyridoxine dependency") AND NOT (TITLE(*eclampsia) OR INDEXTERMS(*eclampsia))) OR (TITLE‐ABS‐KEY(lafora* W/4 (disease OR epilep*)) AND NOT (TITLE(dog OR canine) OR INDEXTERMS(dog OR canine)))) and (TITLE‐ABS‐KEY(refractor* OR resist* OR nonrespons* OR non‐respons* OR intractable))) and (TITLE((randomiz* OR randomis* OR controlled OR placebo OR blind* OR unblind* OR "parallel group" OR crossover or cross‐over) PRE/2 (trial OR method OR procedure OR study)) OR ABS((randomiz* OR randomis* OR controlled OR placebo OR blind* OR unblind* OR "parallel group" OR crossover or cross‐over) PRE/2 (trial OR method OR procedure OR study))) AND ( EXCLUDE(EXACTKEYWORD,"Animal experiment" ) OR EXCLUDE(EXACTKEYWORD,"Animal model" ) )
This diagram refers only to results of the updated searches for the current version of the review
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study
Comparison 1: Zonisamide versus placebo, Outcome 1: 50% responder rate ‐ whole treatment period
Comparison 1: Zonisamide versus placebo, Outcome 2: 50% responder rate ‐ best‐case scenario
Comparison 1: Zonisamide versus placebo, Outcome 3: 50% responder rate ‐ worst‐case scenario
Comparison 1: Zonisamide versus placebo, Outcome 4: 50% responder rate ‐ dose‐effect for Brodie 2005
Comparison 1: Zonisamide versus placebo, Outcome 5: 50% responder rate ‐ dose effect for Faught 2001
Comparison 1: Zonisamide versus placebo, Outcome 6: Withdrawal rates
Comparison 1: Zonisamide versus placebo, Outcome 7: Adverse effects
| Zonisamide compared to placebo for focal epilepsy | ||||||
|---|---|---|---|---|---|---|
| Patient or population: patients with focal epilepsy | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
| Risk with placebo | Risk with zonisamide | |||||
| 50% responder rate (whole treatment period; any dose) | Study population | RR 1.86 | 1429 | ⊕⊕⊕⊝ | Zonisamide 300 mg to 500 mg/day (RR 1.90, 95% CI 1.63 to 2.22; moderate‐certainty evidence) | |
| 248 per 1000 | 461 per 1000 | |||||
| Withdrawal rates (whole treatment period; any dose) | Study population | RR 1.44 | 1156 | ⊕⊕⊕⊝ Moderatea | Zonisamide 300 mg to 500 mg/day (RR 1.59, 95% CI 1.18 to 2.13; moderate‐certainty evidence) | |
| 110 per 1000 | 159 per 1000 | |||||
| Adverse effects: ataxia (whole treatment period; any dose) | Study population | RR 3.85 | 734 | ⊕⊕⊝⊝ | Note that for adverse events, we used a 99% CI. | |
| 17 per 1000 | 67 per 1000 | |||||
| Adverse effects: dizziness (whole treatment period; any dose) | Study population | RR 1.40 | 1429 | ⊕⊕⊕⊝ Moderatea | ||
| 75 per 1000 | 105 per 1000 | |||||
| Adverse effects: fatigue (whole treatment period; any dose) | Study population | RR 1.41 | 1045 | ⊕⊕⊕⊝ Moderatea | ||
| 54 per 1000 | 76 per 1000 | |||||
| Adverse effects: nausea (whole treatment period; any dose) | Study population | RR 1.10 | 805 | ⊕⊕⊕⊝ Moderatea | ||
| 66 per 1000 | 73 per 1000 | |||||
| Adverse effects: somnolence (whole treatment period; any dose) | Study population | RR 1.52 | 1636 | ⊕⊕⊕⊝ Moderatea | ||
| 72 per 1000 | 109 per 1000 | |||||
| *The assumed control risk (ACR) was calculated using median control group risk across the studies that provided data for that outcome.. The corresponding intervention risk in the zonisamide group (and its 95% CI) was based on the assumed risk in the comparison group (ACR) and the relative effect of the intervention (and its 95% CI) and is calculated according to following formula: corresponding intervention risk, per 100 = 100 * ACR * RR. CI: confidence interval; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded once for methodological uncertainties in included studies (unclear risk of bias). Some studies were at high risk of attrition bias; they did not provide reasons for differences between the number of patients in ITT and in per protocol set (PPS). However, the conclusions were unchanged following best‐case (RR 2.22, 95% CI 1.92 to 2.57) and worst‐case (RR 1.44, 95% CI 1.26 to 1.64) scenario analysis. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 50% responder rate ‐ whole treatment period Show forest plot | 7 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.1.1 Any dose | 7 | 1429 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.86 [1.60, 2.17] |
| 1.1.2 300 mg to 500 mg/day | 7 | 1371 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.90 [1.63, 2.22] |
| 1.2 50% responder rate ‐ best‐case scenario Show forest plot | 7 | 1429 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.22 [1.92, 2.57] |
| 1.3 50% responder rate ‐ worst‐case scenario Show forest plot | 7 | 1429 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.44 [1.26, 1.64] |
| 1.4 50% responder rate ‐ dose‐effect for Brodie 2005 Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.4.1 100 mg/day | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.4.2 300 mg/day | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.4.3 500 mg/day | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.5 50% responder rate ‐ dose effect for Faught 2001 Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.5.1 100 mg/day | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.5.2 200 mg/day | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.5.3 400 mg/day | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.6 Withdrawal rates Show forest plot | 6 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.6.1 Any dose | 6 | 1156 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.44 [1.08, 1.93] |
| 1.6.2 300 mg to 500 mg/day | 6 | 1099 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.59 [1.18, 2.13] |
| 1.7 Adverse effects Show forest plot | 8 | Risk Ratio (M‐H, Fixed, 99% CI) | Subtotals only | |
| 1.7.1 Ataxia | 4 | 734 | Risk Ratio (M‐H, Fixed, 99% CI) | 3.85 [1.36, 10.93] |
| 1.7.2 Dizziness | 7 | 1429 | Risk Ratio (M‐H, Fixed, 99% CI) | 1.40 [0.90, 2.18] |
| 1.7.3 Fatigue | 6 | 1045 | Risk Ratio (M‐H, Fixed, 99% CI) | 1.41 [0.79, 2.53] |
| 1.7.4 Nausea | 5 | 805 | Risk Ratio (M‐H, Fixed, 99% CI) | 1.10 [0.58, 2.10] |
| 1.7.5 Somnolence | 8 | 1636 | Risk Ratio (M‐H, Fixed, 99% CI) | 1.52 [1.00, 2.31] |
| 1.7.6 Agitation or irritability | 4 | 598 | Risk Ratio (M‐H, Fixed, 99% CI) | 2.35 [1.05, 5.27] |
| 1.7.7 Anorexia | 6 | 1181 | Risk Ratio (M‐H, Fixed, 99% CI) | 2.74 [1.64, 4.60] |
