Table 5.

Adverse event data (narrative report)

Trial	Adverse event data1	Summary of reported results
		Phenytoin (PHT)	SV (Sodium Valproate)
Callaghan 1985	All adverse events developed (by drug) and adverse events leading to discontinuation of treatment	PHT (n = 58): gum hypertrophy (n = 2), rash (n = 2), ataxia (n = 2)	SV (n = 64): weight gain (n = 4 – all discontinued treatment), drowsiness (n = 2), aggressive behaviour (n = 1 – discontinued treatment)
Craig 1994	Adverse event frequency (spontaneous reports)2 Discontinuations due to adverse events3	PHT (n = 25): unsteadiness (n = 9), sleepiness (n = 7), drowsiness (n = 2), impaired concentration (n = 2), confusion (n = 1), constipation (n = 1), diarrhoea (n = 1), dysarthria (n = 1), lethargy (n = 1), nystagmus (n = 1), rash (n = 1), tired legs (n = 1) PHT discontinuations (n = 6): rash (n =1), diarrhoea (n = 1), confusion (n = 1), unsteadiness (n = 1), constipation (n = 1), sleepiness (n = 1)	SV (n = 17): unsteadiness (n = 2), sleepiness (n = 3), tremor (n = 5), oedema (n = 3), alopecia (n = 2), depression (n = 2), weight gain (n = 2) SV discontinuations (n = 2): weight gain and depression (n = 1), unsteadiness (n =1)
Czapinski 1997a	“Exclusions” due to adverse events or no efficacy4	Proportion “excluded”: PHT: 33.3%	Proportion “excluded”: SV: 23.3%
De Silva 1996	“Unacceptable” adverse events leading to drug withdrawal5	PHT (n = 54): drowsiness (n = 2), skin rash (n = 1) blood dyscrasia (n = 1), hirsutism (n = 1)	SV (n = 49): behavioural (n = 1), tremor (n = 1)
Forsythe 1991	No adverse event data reported (Withdrawal data only reported)	1 participant (PHT) withdrew from the study due to depression and anorexia	No adverse event data (or withdrawals due to adverse events) reported
Heller 1995	“Unacceptable” adverse events leading to drug withdrawal5	PHT (n = 63): myalgia (n = 1), irritability (n = 1)	SV (n = 61): dizziness (n = 2) abnormal liver function test (n = 1)
Ramsay 1992	Most common adverse events (by treatment group)6	PHT (n = 50): dyspepsia (n = 1), nausea (n = 2), dizziness (n = 2), somnolence (n = 5), tremor (n = 2), rash (n = 4)	SV (n = 86): dyspepsia (n = 7), nausea (n = 10), dizziness (n = 5), somnolence (n = 8), tremor (n = 5), rash (n = 3)
Rastogi 1991	Commonest adverse events (reported as percentages by treatment group)6	PHT (n = 45): gum hyperplasia (17.7%), nystagmus (13.33%), ataxia (2.2%), gastrointestinal disturbances (4.44%), drowsiness (4.44%)	SV (n = 49): gastrointestinal disturbances (12%), drowsiness (6.12%), weight gain (2.04%)
Shakir 1981	Adverse events (narrative description)2	PHT (n = 15): 1 case of ataxia, 5 cases of acne	SV (n = 18): 2 cases of gastrointestinal symptoms, 2 cases of hair loss, 4 cases of weight gain
Thilothammal 1996	Assessment of adverse events2	PHT (n = 52): 33 participants reported at least one side effect Reported frequencies: gingival hypertrophy (n = 30), ataxia (n = 13), sedation (n = 12), nausea and vomiting (n = 1) Other reported adverse events (no frequencies): nystagmus, confusion	SV (n = 48): 15 participants reported at least one side effect Reported frequencies: hyperactivity (n = 6), impaired school performance (n = 4), severe skin allergy (n = 1)
Turnbull 1985	Withdrawals due to dose‐related and idiosyncratic adverse events	PHT (n = 70): 11 withdrawals due to dose‐related adverse events (nystagmus, ataxia, tremor, diplopia and mental change) 5 withdrawals due to idiosyncratic adverse events (skin eruption, erythroderma and jaundice)	SV (n = 70): 9 withdrawals due to dose‐related adverse events (tremor, irritability, restlessness and alopecia) No withdrawals due to idiosyncratic adverse events

¹Adverse event data, as reported narratively in the publications. Adverse event data were not requested in original IPD requests but will be for all future IPD requests. For numbers of withdrawals due to adverse events in studies for which IPD were provided (De Silva 1996; Heller 1995; Ramsay 1992; Turnbull 1985) see Table 6. ²Participants may report more than one adverse event. ³The published paper, Craig 1994, reports on a subset of 38 participants, so the adverse event data summary applies only to this subset. IPD were provided for 166 participants (no additional adverse event data provided). ⁴Czapinski 1997a is an abstract only so very little information is reported. ⁵Participants may have withdrawn due to adverse event alone or a combination of adverse events and poor efficacy (seizures). ⁶Most commonly reported adverse events only, no indication of overall frequency of all adverse events.