Table 3.
Details of number of dogs, 95 % CI affected cases, AED doses and serum levels, treatment period and adverse effects
| Studies | AED | No of dogs treated | Prevalence | 95 % CI affected cases | Doses of AEDs | Serum levels of AEDs | Treatment period | Body system affected and adverse effects | Most common adverse effects | Adverse effect type |
|---|---|---|---|---|---|---|---|---|---|---|
| Boothe et al. 2012 | PBr | 23 | 78.5 % | 61.7 %–95.3 % | mean, 30.6; range, 26–35 mg/kg PO BID | mean, 1.9 +/− 0.6; range, 0.9–3.3 mg/ml | approximately 6 m | Neurological (ataxia, hyperactivity, sedation), GI (vomiting, diarrhoea, PP), PU, PD | sedation, hyperactivity, ataxia, PD, PU | I |
| Pearce 1990 | PBr as an adjunct to PHB | 10 | 40 % | 9.6 %–70.4 % | PBr: 22 mg/kg PO SID (dose increases occurred) PHB: median, 3.3; mean, 3.8 mg/kg PO BID (dose was reduced by a mean of 50 % in 7/10 dogs during the PBr treatment) |
PBr: mean, 810; range, 500–1625 mg/l PHB: mean, 29.7; range, 17–45 ug/ml |
median, 7; mean, 7.8 m | Neurological (ataxia, sedation, hyperactivity), PU, PD | ataxia, letargy, PU, PD | I |
| March et al. 2002 | PBr | 6 | 20 % | −12.0 %−52.0 % | 30 mg⁄kg PO BID | median, 245; range, 178–269 mg/dL | 3.9 m (adverse effects occurred after this period when dose adjustments occurred (NA)) |
Neurological (ataxia, paraparesis, hyperactivity) | ataxia, paraparesis | I |
| Rossmeisl et al. 2009 | PBr as an adjunct to PHB and/or other AEDs | 1298 | 2 % | 1.2 %–2.8 % | PBr: 44.9+/−1.7 mg/kg PO SID PHB: 6.3+/−0.4 mg/kg PO SID |
PBr: 3.7+/−0.3 mg/ml PHB: 31.4+/−1.2 μg/dl |
NA | Neurological (sedation, ataxia, paraparesis, tetraparesis) | sedation, ataxia, paraparesis, tetraparesis | I |
| Dayrell-Hart B et al. 1996 | PBr | 238 | 10.9 % | 6.9 %–14.9 % | NA | 21 affected dogs had >2.3 mg/ml and 5 affected dogs had <0.5 mg/ml | NA | Neurological (ataxia, sedation) | ataxia, sedation | I |
| Podell and Fenner 1993 | PBr as an adjunct to PHB and/or other AEDs | 23 | 78 % | 61.1 %–94.9 % | PBr: mean, 20.75; range, 13–40 PO BID PHB: NA |
PBr: 161 mg/dl PHB: 37.8 mcg/ml |
mean, 15; range, 4–33 m | Neurological (ataxia, sedation), GI (PP), ClinPath (increased serum chloride), PU, PD | PU, PD, PP, sedation | I |
| Chang et al. 2006 | PBr (monotherapy or as an adjunct to PHB) | Monotherapry: 4 Adjunctive Therapy: 10 |
Monotherapry: 62.5 % Adjunctive Therapy: 95 % |
Monotherapy: 15.0–110.0 % Adjunctive therapy: 81 %–109 % |
NA | NA | median, 18; range, 3–72 m | Neurological (ataxia, hyperactivity), Dermatological (pruritus), GI (PP), The adjunctive therapy group had also PU, PD and vomiting/diarhoea |
Ataxia, hyperactivity, pruritus, PP | I |
| Yohn et al. 1992 | PBr as an adjunct to PHB | 1 | NA | NA | NA | 2.7 mg/ml | 1 m | Neurological (sedation, ataxia, paraparesis, anisocoria) | NA | I |
| Kantowitz et al. 1999 | PBr (monotherapy or as an adjunct to PHB) | Monotherapry: 15 Adjunctive therapy: 8 |
NA | NA | NA | Monotherapy: median, 1985; range, 500–3419 mg/dL Adjunctive therapy: PBr: median, 1399; range, 584–2438 mg/dL. PHB: median, 22.4; range, 10.9–40 μg/ml |
Monotherapy: median, 14.5; range, 3–37 m Adjunctive therapy: PBr: median, 5; range, 3–72 m. PHB: median, 22; range, 3–96 m |
Monotherapy: Normal Adjunctive therapy: Endocrine (decreased total T4, free T4) |
NA | I |
| Srivastava et al. 2013 | PBr as an adjunct to PHB | 6 | 100 % | 100 % | PBr: 30 mg/kg PO SID PHB: Initially 2.5 mg/kg, then 5 mg/kg PO SID. |
NA | mean, 11.50+/− 1.23; range, 8–15 m (on PHB). Then, PBr started and 3 m later a reduction of 50 % in the dose of PHB was performed. After 6 m, PHB was completely withdrawn. |
Neurological (ataxia), GI (hepatoxicity, anorexia, PP), ClinPath (increased ALT, ALP, AST, bile acids), PU, PD (polyphagia, PU, PD appeared after 1–1.5 years of PBr therapy) |
PU, PD, PP | I |
| Shaw et al. 1996 | PBr as an adjunct to PHB | 1 | NA | NA | PBr: 20 mg/kg PO SID PHB: 3.75 mg/kg PO BID |
PBr: 1100 mg/l. PHB: 20.4 μg/ml |
Approximately 21 m | After PBr initiation: Neurological (sedation, ataxia) | NA | I |
| Paull et al. 2003 | PBr | 5 | 60 % | 17.1 %–102.9 % | Initially 100 mg/kg PO BID for 2 days. Then, 30 mg/kg PO SID for 180 days. |
range, 88–300 mg/dL (only one dog was >300 mg/dl) | 6 m | Endocrine (Euthyroid sick syndrome with decreased TT4 and normal TSH) Placebo group had the same results |
NA | I |
| Stabile et al. 2014 | PBr as an adjunct to PHB | 1 | NA | NA | PBr: Initially, 400 mg/kg divided in six daily doses for four days. Then, 14 mg/kg PO BID PHB: Initially, 2.7 mg/kg, then 5 mg/kg and finally 6.4 mg/kg PO BID. |
PBr: 15.9 mg/ml; PHB: 23.7 μg/ml | ≥26 m | Neurological (sedation, ataxia, generalised appendicular repetitive myoclonus), ClinPath (pseudohyperchlormia, increased ALP) | NA | I & II |
| Gaskill and Kimber 2010 | PBr | 32 | 85.9 % | 73.8 %–98.0 % | NA | NA | 12 m | Neurological (ataxia, sedation, hyperactivity, aggression), GI (PP, anorexia, vomiting, diarrhoea, pancreatitis), Dermatological (skin problems), ClinPath (increased ALP, ALT, amylase, lipase), PU, PD | vomiting, sedation, PP, PU, PD | I & II |
| Volk et al. 2008 | PBr as an adjunct to PHB (prior to addition of other AEDs) | 14 | 100 % | 100 % | PBr and PHB: NA but were within normal reference values | PBr: 1.7+/−0.4 mg/ml PHB: 35.5+/−6.3 μg/ml |
≥2–6 m | Neurological (ataxia, aggression), GI (PP, vomiting, pancreatitis), ClinPath (increased ALT, ALP) PU, PD | increased ALT, ALP, ataxia, aggression | I & II |
| Gaskill et al. 2000 | PBr as an adjunct to PHB | Clinical trial: 6 Case series: 19 |
Clinical trial: 50 % Case series: 37 % |
Clinical trial: 10.0 %–90.0 % Case series: 15.3 %–58.7 % (pancreatitis); 47.5 %–89.3 % (increased enzymes only) |
Clinical trial: NA Case series: NA |
Clinical trial: NA Case series: PBr: range, 12.5-37.5 mmol/L; PHB: range, 54–190 imol/L |
Clinical trial: approximately 1 year Case series: NA |
GI (pancreatitis, increased amylase and/or lipase activities) | pancreatitis, increased amylase and/or lipase activities | II |
| Steinmetz et al. 2012 | PBr as an adjunct to PHB | 1 | NA | NA | 101.19 mg/kg SID PO (added at the beginning of the 4th year) PHB: 4.9 mg/kg BID PO |
PBr: 45 mmol/l PHB: 168.52 μmol/l |
48 m (adverse effect occurred after the 48 m) | Neurological (neuromyopathy with generalised low motor signs) | NA | II |
| Mackay and Mitchell 1998 | PBr as an adjunct to PHB | 1 | NA | NA | PBr: Initially 200 mg/kg PO BID for 3 days, then 30 mg/kg PO SID PHB: 5 mg/kg PO BID. |
PBr: NA. PHB: 126 umol/L |
3 d (signs started 3 d after the loading dose of PBr was initiated) |
ClinPath (artifactual hyperchloraemia and negative anion gap), Neurological (pacing, disorientation), GI (vomiting) The Neurological and GI signs were attributed to hypercloraemia |
NA | II |
| Boynosky and Stokking 2014 | PBr as an adjunct to PHB | 2 | NA | NA | Initially 40 mg/kg PO SID, then 60 mg/kg PO SID (case 1) or 86 mg/kg PO SID (case 2) | Case 1: 2.9 mg/mL; Case 2: initially 0.8, then 3 mg/ml (after 7.5 months of treatment) | 12 m [adverse effects occured 3 (case 1) and 8 (case 2) m after the dose increase] |
Dermatological (panicculitis) accompanied by sedation and anorexia | NA | II |
| Steiner et al. 2008 | PBr (monotherapy or as an adjunct to PHB) | Monotherapy: 98 Adjunctive therapy: 121 |
14 % | Monotherapy: 8.2 %–22.4 % Adjunctive: 5.9 %–17.3 % |
NA | range, 0.5–4.2 mg/ml (majority of dogs; range, 1–2 mg/ml) | NA | ClinPath (increased cPLI) | NA | II |
| Bizzeti et al. 2006 | PBr as an adjunct to PHB | 7 | 43 % | 6.1 %–79.4 % | NA | NA | NA | Pancreatitis, ClinPath (increased amylase, lipase,cPLI) | NA | II |
Abbreviations: AED(s) anti-epileptic drug(s), BID bis in die (twice daily), Chloraz Chlorazepate, CSF cerebrospinal fluid, CL confidence level, Gaba Gabapentin, IE idiopathic epilepsy, LEV Levetiracetam, m month(s), NA Not Available, PHB phenobarbital, PD polydipsia, PU polyuria, PP polyphagia, PBr potassium bromide, Prim primidone, PO per os, SID semel in die (once daily), TID ter in die (three times daily); TPM Topiramate; w week(s), y year(s)