Last reviewed: June 2018
Last updated: May  2018

European Medicines Agency (EMA) strengthens measures to avoid use of valproate medicines in pregnancy

In March 2018 the EMA announced stronger measures aimed at avoiding the exposure of babies to valproate medicines in the womb. Under the new restrictions, valproate medicines are contraindicated in bipolar disorder during pregnancy due to the high risk of congenital malformations and developmental problems in the child.

Valproate medicines must not be used in female patients of childbearing potential unless there is a pregnancy prevention programme in place and certain conditions are met. These include:

  • an assessment of the patient’s potential for becoming pregnant

  • pregnancy tests before starting and during treatment as needed

  • counselling about the risks of valproate treatment and the need for effective contraception throughout treatment

  • a review of ongoing treatment by a specialist at least annually

  • a risk acknowledgement form that patients and prescribers will go through at each such annual review to confirm that appropriate advice has been given and understood.

The EMA said the new measures were put in place because of evidence suggesting that information on the risks of valproate use in pregnancy was still not getting through to women despite earlier steps aimed at ensuring this.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • major depressive episode(s)
  • episode(s) of manic or mixed episodes
  • episode(s) of hypomania
  • inflated self-esteem or grandiosity
  • decreased need for sleep
  • more talkative than usual, or feels pressure to keep talking
  • flight of ideas, or subjective experience that thoughts are racing
  • distractibility
  • increase in goal-directed activity or psychomotor agitation
  • excessive involvement in pleasurable activities that have a high potential for adverse consequences
  • functional impairment
  • no substance misuse
  • no underlying medical cause
  • not due to somatic antidepressant treatment or other prescribed medication

Risk factors

  • FHx of bipolar disorder
  • onset of mood disorder prior to 20 years of age
  • stressful life events
  • previous hx of depression
  • lifetime hx of a substance misuse disorder
  • presence of an anxiety disorder
  • obesity
  • cardiovascular disease

Diagnostic investigations

1st investigations to order

  • Primary Care Evaluation of Mental Disorders (PRIME-MD)
  • Patient Health Questionnaire (PHQ-9)
  • Mood Disorder Questionnaire (MDQ)
  • Composite International Diagnostic Interview (CIDI)
  • Bipolarity Index
  • Young Mania Rating Scale (YMRS)
  • FBC
  • thyroid function tests
  • serum vitamin D
  • toxicology screen
Full details

Investigations to consider

  • fasting lipid profile
  • fasting glucose
  • MRI brain
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Assistant Professor of Psychiatry

University of Texas Health Science Center

Houston

TX

Disclosures

SS has received intravenous citalopram for research from Lundbeck UK and participated as a speaker organised by Global Medical Education (GME). SS has third party indirect share in the form of convertible note in Flow MedTech, Inc (a medical device start-up company).

Dr Sudhakar Selvaraj would like to gratefully acknowledge Dr Prashant Gajwani and Dr David J. Muzina, previous contributors to this topic. PG has served on the speakers' bureau for Merck and Sunovion. DJM is an author of a number of references cited in this topic. DJM has previously received honoraria for research support from Repligen Co. He has also previously received honoraria as a speaker and/or advisor from AstraZeneca, Pfizer, BMS, Wyeth, Sepracor, and GSK. DJM is a full-time employee of Medco.

Peer reviewers VIEW ALL

Head

Mood Disorders Psychopharmacology Unit

University Health Network

Associate Professor of Psychiatry and Pharmacology

University of Toronto

Ontario

Canada

Disclosures

RM has received research funds from Stanley Medical Research Institute and National Alliance for Research on Schizophrenia and Depression (NARSAD). RM is on the advisory boards for AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, Shire, and Schering-Plough. RM is on the speakers' bureau for Janssen-Ortho, AstraZeneca, Eli Lilly, Lundbeck, Biovail, and Wyeth. RM has received research grants from Eli Lilly, Janssen-Ortho, and Shire.

Professor of Psychological Medicine

University of Newcastle

Honorary Professor

Psychological Treatments Research

Institute of Psychiatry

London

University Department of Psychiatry

Royal Victoria Infirmary

Newcastle upon Tyne

UK

Disclosures

JS has received remuneration for attending advisory boards for AstraZeneca, BSM-Otsuka, Eli Lilly, GSK, and Sanofi-Aventis.

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