Comparative efficacy and safety of alternatives to sodium valproate in the management of bipolar affective disorder in people of child-bearing age: a narrative review by the European Society of Clinical Pharmacy's mental health specialist interest group.
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Authors
Fitzgerald, Ita
Bayraktar, Izgi
Eiden, Birgit
Gittins, Rosalind
Magni, Erica
Humbert-Claude, Marie
Molitschnig, Lara-Turiya
Darm, Paula
Waksmundzka-Walczuk, Anna
Riesenhuber, Nikolaus
Issue Date
2025-04-28
Type
Journal Article
Review
Review
Language
en
Keywords
Bipolar affective disorder , Bipolar disorder , Mood stabilisers , Narrative review , Pregnancy , Sodium valproate , Teratogenicity
Alternative Title
Abstract
The European Medicines Agency has recommended a series of restrictions on the use of sodium valproate (valproate) following research linking its exposure in utero to adverse congenital and neurodevelopmental effects in offspring. Recent research has highlighted a potential increased risk of neurodevelopmental disorders in children born to males taking valproate prior to conception. Clinicians and patients require guidance regarding suitable alternatives.
To provide an overview of suitable alternatives to valproate in the management of bipolar disorder.
A narrative review was conducted. Only medications with an established evidence base in managing different phases of bipolar disorder and endorsed within clinical practice guidelines were considered. Eligible guidelines included those (i) where recommendations were informed by a formal guideline development process and (ii) published in English within the last 15 years. REPROTOX® was chosen as the primary information source regarding reproductive safety of alternative medications.
Of all second-generation antipsychotics, quetiapine should be considered a first-line alternative to valproate. Lithium has been associated with an increased risk of cardiac malformations, especially Ebstein anomaly, following in utero exposure. However, given its robust efficacy as an antimanic agent and the absolute risk of cardiac abnormalities being low, it's use can still be considered in individuals of child-bearing potential with appropriate monitoring. Carbamazepine treatment should be avoided due to concerns for teratogenicity. Although considered safe in pregnancy, lamotrigine is largely effective at preventing relapse of bipolar depression. Thus, lamotrigine offers limited clinical utility as an alternative to valproate.
Specific recommendations are made regarding alternatives to valproate in managing bipolar disorder.
To provide an overview of suitable alternatives to valproate in the management of bipolar disorder.
A narrative review was conducted. Only medications with an established evidence base in managing different phases of bipolar disorder and endorsed within clinical practice guidelines were considered. Eligible guidelines included those (i) where recommendations were informed by a formal guideline development process and (ii) published in English within the last 15 years. REPROTOX® was chosen as the primary information source regarding reproductive safety of alternative medications.
Of all second-generation antipsychotics, quetiapine should be considered a first-line alternative to valproate. Lithium has been associated with an increased risk of cardiac malformations, especially Ebstein anomaly, following in utero exposure. However, given its robust efficacy as an antimanic agent and the absolute risk of cardiac abnormalities being low, it's use can still be considered in individuals of child-bearing potential with appropriate monitoring. Carbamazepine treatment should be avoided due to concerns for teratogenicity. Although considered safe in pregnancy, lamotrigine is largely effective at preventing relapse of bipolar depression. Thus, lamotrigine offers limited clinical utility as an alternative to valproate.
Specific recommendations are made regarding alternatives to valproate in managing bipolar disorder.
Description
Citation
Fitzgerald I, Bayraktar I, Eiden B, Gittins R, Magni E, Humbert-Claude M, Molitschnig LT, Darm P, Waksmundzka-Walczuk A, Riesenhuber N, Stuhec M, Tašková I, Hahn M. Comparative efficacy and safety of alternatives to sodium valproate in the management of bipolar affective disorder in people of child-bearing age: a narrative review by the European Society of Clinical Pharmacy's mental health specialist interest group. Int J Clin Pharm. 2025 Apr 28. doi: 10.1007/s11096-025-01919-x. Epub ahead of print. PMID: 40293641.
Publisher
License
© 2025. The Author(s).
Journal
International journal of clinical pharmacy
Volume
Issue
PubMed ID
DOI
10.1007/s11096-025-01919-x
10.1016/S1474-4422(24)00141-8
10.1038/s41380-021-01334-4
10.1111/bdi.12609
10.1111/bdi.13135
10.1080/15622975.2017.1384850
10.3109/15622975.2013.770551
10.3109/15622970903555881
10.1080/15622970902823202
10.1038/s41380-020-00946-6
10.1038/s41380-021-01334-4
10.1016/j.euroneuro.2021.10.003
10.1038/s41380-024-02697-0
10.1016/S2215-0366(23)00199-2
10.1001/archgenpsychiatry.2011.1870
10.1016/j.eclinm.2022.101690
10.1007/s40263-022-00908-2
10.1176/appi.ajp.2018.17040393
10.1016/S1474-4422(24)00141-8
10.1038/s41380-021-01334-4
10.1111/bdi.12609
10.1111/bdi.13135
10.1080/15622975.2017.1384850
10.3109/15622975.2013.770551
10.3109/15622970903555881
10.1080/15622970902823202
10.1038/s41380-020-00946-6
10.1038/s41380-021-01334-4
10.1016/j.euroneuro.2021.10.003
10.1038/s41380-024-02697-0
10.1016/S2215-0366(23)00199-2
10.1001/archgenpsychiatry.2011.1870
10.1016/j.eclinm.2022.101690
10.1007/s40263-022-00908-2
10.1176/appi.ajp.2018.17040393
ISSN
2210-7711