Withdrawal of valproic acid treatment during pregnancy and seizure outcome: Observations from EURAP.
Based on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesian statistics, we compared seizure control in pregnancies where VPA was withdrawn (withdrawal group, n = 93), switched to another AED (switch group, n = 38), or maintained (maintained-therapy group, n = 1,588) during the first trimester. The probability of primarily or secondarily generalized tonic-clonic seizures (GTCS) was lower in the maintained-therapy group compared with the other two groups, both in the first trimester and for the entire duration of pregnancy. GTCS were twice as common during pregnancy in the withdrawal (33%) and switch groups (29%) compared with the maintained-treatment group (16%). Limitations in the data and study design do not allow to establish a cause-effect relationship between treatment changes and seizure outcome, but these observations provide a signal that withdrawal of, or switch from, VPA during the first trimester could lead to loss of seizure control, and highlight the need for a specifically designed prospective observational study.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Torbjörn
T
Tomson
Epilepsy Center, Department of Neurophysiology and Experimental Epileptology, I.R.C.C.S. Neurological Institute "Carlo Besta" Foundation, Milan, Italy.
Dina
D
Battino
Department of Clinical Sciences and Community, Laboratory of Medical Statistics, Biometry and Epidemiology "GA Maccacaro," University of Milan, Milan, Italy.
Erminio
E
Bonizzoni
Belfast Health and Social Care Trust, Belfast, Ireland.
John
J
Craig
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.|Epilepsy Institute in The Netherlands (SEIN), Heemstede, The Netherlands.
Dick
0000-0001-9580-624X
D
Lindhout
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.|Clinical Trial Center, C. Mondino National Neurological Institute, Pavia, Italy.
Emilio
E
Perucca
The Epilepsy Clinic, Department of Neurology, Rigshospitalet University State Hospital, Copenhagen, Denmark.
Anne
A
Sabers
Department of Neurology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala State, India.
Sanjeev V
SV
Thomas
Departments of Medicine and Neurology, University of Melbourne, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Frank
F
Vajda
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D001499:Bayes Theorem; D015331:Cohort Studies; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007391:International Cooperation; D064887:Observational Studies as Topic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011264:Pregnancy Trimesters; D012042:Registries; D013226:Status Epilepticus / Q000188:drug therapy / Q000453:epidemiology; D013375:Substance Withdrawal Syndrome; D014635:Valproic Acid / Q000627:therapeutic use*; D055815:Young Adult
D000927:Anticonvulsants; D014635:Valproic Acid
Epilepsy; Pregnancy; Seizures; Valproic acid