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. Author manuscript; available in PMC: 2019 Oct 1.
Published in final edited form as: Expert Rev Pharmacoecon Outcomes Res. 2018 Jun 28;18(5):487–503. doi: 10.1080/14737167.2018.1489243

Table 4.

AED adverse effect impact inventory.

Societal studies Health care sector studies
Balabanov 2006 Balabanov 2008 Knoester 2007 Maltoni 2013 Messori 1998 Bolin 2010 Bolin 2013 Clements 2013 Hawkins 2005 Remak 2003 Remak 2004 Simoens 2012 Spackman 2007 Suh 2009 Vera-Llonch 2008
Drugs compared in the studya
 Phenytoin (PHT) [1953]
 Carbamazepine (CBZ) [1968] ✔ ✔ ✔ ✔ ✔
 Valproate/Valproic add (VPA) [1978] ✔ ✔ ✔ ✔
 Gabapentin (GBP) [1993] ✔ ✔
 Lamotrigine (LTG) [1994] ✔ ✔ ✔ ✔ ✔ ✔ ✔ s
 Topiramate (TPM) [1996] ✔ ✔ ✔ ✔ ✔
 Tiagabine (TGB) [1997] ✔
 Levetiracetam (LEV) [1999] ✔ ✔ ✔
 Oxcarbazepine (OXC) [2000] ✔ ✔
 Zonisamide (ZNS) [2000] ✔
 Pregabalin (PGB) [2004] ✔
 Lacosamide (LAC) [2008] ✔ ✔ ✔
 Rufinamide (RUF) [2008] ✔
 Vigabatrin (VGB) [2009] ✔
 Clobazam (CLB) [2011] ✔ ✔
 Ezogabine (retigabine) (EZG) [2011] ✔
Adverse effects by overall type, specific effect, and associated drugs (listeid by abbreviation)b
 AE in general considered (nonspecific AEs) ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ - ✔ - ✔
 Degree AEs in general considered in utility measurement (D, directly as an impact of AED; I, indirectly as part of health state; NA, not applicable; NC, not considered D D NA I I I D NC NC NC NC I NC D D
 ○ Details about AEs provided - ✔ ✔ LI ✔ LI ✔ - ✔
 ○ Cardiovascular AE
  § Arrhythmia, conduction abnormality LAC, PGB, EZG, RUF - . -
  § Hypertension LEV, VGB _ _
  § Edema (peripheral edema, edema) PGB, VPA, VGB -
 § Syncope LAC
 ○ Cosmetic AE
  § Gingival hyperplasia PHT
  § Alopecia VPA ✔VPA ✔All
  § Facial abnormality PHT
 ○ Dermatological AE
  § Serious skin reactions (SJS, TEN) CBZ, CLB, GBP, LAC, LTG, LEV, OXC, PHT, PGB, RUF, TGB, VPA, ZNS - ✔LTG ✔LTG -
  § Multi-organ hypersensitivity (DRESS) CBZ, GBP, LAC, LTG, OXC, PHT, RUF, VPA, ZNS -
  § Skin discoloration EZG
  § Other skin reactionsc CLB, PHT, VGB ✔All ✔All
 ○ Endocrinology AE
  § Osteoporosis/osteopenia/osteomalacia/vit D deficiencyPHT, TPM, ZN - -
  § Weight gain PGB, VGB ✔VPA ✔Al _
  § Weight loss TPM ✔Al ✔All
  § Hyponatremia/low sodium level CBZ, OXC - -
  § Metabolic acidosis TPM, ZNS - -
  § Hypothyroidism oxc -
 ○ Gastrointestinal AE
  § Nausea/vomiting CBZ, LAC, LTG, LEV, OXC, PHT, RUF, TGB, TPM, VPA, VGB - UCBZ - - - - ✔All LI - ✔All - - ✔All - ✔
  § Hepatotoxicity/impairment/associated symptomsdCBZ, OXC, PHT, TPM,VPA - - - - - - - -
  § Diarrhea TPM, VPA, VGB, ZNS - - - LI - - - -
  § Anorexia TPM, ZNS - - - - - -
  § Constipation PHT, VGB -
  § Abdominal pain OXC, VPA - - - - -
  § Others: dysgeusia(metallic taste)PHT, dyspepsiaVPA, pancreatitisVPA, sialorrheaCLB, xerostomia PGB - - - - - - -
 ○ Hematologic and oncologic AE
  § Blood dyscrasiaseCBZ, LTG, LEV, OXC, PHT, RUF, VPA - - - - - - - - -
  § Anemia CBZ, LTG, PHT, VGB - - - - - - - - -
  § Thrombocytopenia CBZ, LEV, LTG, PHT, PGB, VPA - - - - - - - - - - -
  § Others: leukopeniaRUF, lymphadenopathyPHT -
 ○ Nephrology AE
  § Renal calculus TPM, ZNS - - - ✔TPM - - -
  § Urinary retention EZG - -
 ○ Neurological AE
  § CNS depressionfCBZ, CLB, GBP, LAC, LTG, LEV, OXC, PHT, PGB, EZG, RUF, TGB, TPM, VGB, ZNS - UALL - - - - ✔All - - - - - - - ✔
  § Tremor LAC, OXC, PHT, PGB, EZG, TGB, VPA, VGB - ✔VPA - - - - - - - -
  § Vision issuegLAC, OXC, PHT, PGB, EZG, TPM, TGB, VPA, VGB - - - - - - - - - - - ✔
  § Cognitive: dysfunction/confusion/memory impairment CBZ, LEV, LAC, OXC, PHT, PGB, RUF, EZG, TGB, TPM, VGB, VPA, ZNS - - - - - - - - ✔All - - ✔All - ✔
  § Somnolence: GBP, LEV, OXC, PGB, EZG, RUF, TPM, ZNS - - - ✔All LI - - - - - ✔
  § Headaches LAC, LEV, OXC, PHT, PGB, RUF, VPA, VGB - UCBZ - - - - - - - - - - ✔
  § Worsening of seizure (frequency, severity) VGB -
  § Status epilepticus TGB, VGB - -
  § Motor abnormalityh CBZ, CLB, GBP, LAC, LEV, LTG, OXC, PHT, PGB, PGB, EZG, RUF, TGB, TPM, VPA, VGB, ZNS - - - - - - ✔All - - - - - - - ✔
  § Fatigue/lethargy CLB, GBP, LAC, LTG, LEV, OXC, PGB, EZG, RUF, TPM, VGB, ZNS - - - - - ✔All - - - - - - - ✔
  § Abnormal sensationi PHT, TPM - - - - -
  § Weakness LEV, TGB, VPA - - - - - - ✔
  § Insomnia PHT, VPA, VGB - - - - -
  § Vertigo OXC, PHT - -
  § Peripheral neuropathy PHT, VGB -
  § Others: Anterograde amnesiaCLB, brain atrophyVPA, catatoniaVPA, cerebral atrophyVPA, painVPA, paradoxical reactionsCLB - - - - - -
 ○ Psychiatric AE (e.g., suicidal ideation, mood change, depression, etc.)
  § Suicidal ideation/thinking/behavior All AEDs
  § Mood issuesj CBZ, CLB, EZG, GBP, LEV, PHT, TGB, VPA, VGB, ZNS - - - - - - - - - - - - - - -
  § Psychiatric effects CBZ, GBP, LEV, EZG, TPM, ZNS - UCBZ - - - - - - - -
  § Others: DepressionLEV - - - - - - - - - - -
 ○ Respiratory related AEs - - -
  § URI/pneumonia CLB, VGB
  § Respiratory issuesk LEV, TPM, VGB - -
 o Immune related AEs - - - - - - - - -
  § AnaphylaxiskGBP, LEV, OXC, PGB - - - - - -
  § Infection: GBP, LEV, PGB, TGB, TPM, VPA aceptic meningitisLTG, otitis mediaVGB - - - - - - - - - - -
  § Others: systemic lupus erythematosusPHT
 ○ Other AEs
  § Fever CLB, TPM, VGB - LI - - -
  § Flu-like symptoms VPA - - - -
  § Others: hypothermiaVPA, oligohydrosis/hyperthermiaTPM, rhabdomyolysisPGB, sulfonamide allergyZNS - - - - - - - -
a

Arranged by year of U.S. Food and Drug Administration (FDA) approval (indicated in []); second-line therapy in analyses indicated by superscript ‘S’.

b

Drug abbreviations in BOLD indicate reactions listed in Warnings/Precautions; BOLD underlined indicate reactions also listed as Boxed Warning by US FDA.

c

E.g. rash, erythroderma, blistering, Lupus-like symptoms, xeroderma, etc.

d

E.g. hyperammonemia/encephalopathy.

e

E.g. agranulocytosis, aplastic anemia, neutropenia, leukopenia, pancytopenia.

f

Lack of coordination, slowed or slurred speech, drowsiness, dizziness.

g

Diplopia, nystagmus, permanent vision loss, increase IOP, eye pain, retinal abnormalities, visual field defects.

h

E.g. ataxia, myasthenia, dyspraxia, hyperkinesia, psychomotor agitation, psychomotor retardation, psychomotor slowing.

i

E.g. hypoesthesia, paresthesia

j

E.g. agitation, aggression, anger, anxiety, emotional lability, hostility, irritability, nervousness, paranoia, neurosis, psychosis.

k

Rhinitis, cough, pharyngitis, bronchitis, dyspnea, epistaxis, sinusitis, nasopharyngitis.

l

Hypersensitivity reaction, angioedema.

✔ ‘yes’, included; ‘-’ no, not discussed.

AE: adverse effect; ALL: all drugs included in the analysis; DRESS: drug reaction with eosinophilia and systemic symptoms; LI: identified, but determined likely insignificant in context of analysis; SJS: Stevens–Johnson syndrome; TEN: toxic epidermal necrolysis; U: unknown if included, not enough information provided.