Psych · Psychopharmacology — valproate
Valproate
Also known as Sodium valproate · Valproic acid · Divalproex · Depakote · Epilim · Semisodium valproate · VPA
Exam-exhaustive fellowship psychopharmacology of valproate/divalproex — acute mania and oral loading, trough levels, BALANCE maintenance limits versus lithium, pregnancy-prevention hierarchy (EURAP, NEAD, ASD risk), PCOS-like endocrine effects, hyperammonaemic encephalopathy, LFT/platelet monitoring, and lamotrigine interaction. FRANZCP-primary, globally tagged.
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Target exams
Red flags
- Valproate in a person who can become pregnant without documented pregnancy-prevention counselling — major teratogen; not routine bipolar care
- New confusion, lethargy or reduced awareness on valproate — check ammonia for hyperammonaemic encephalopathy even if LFT relatively preserved
- Acute abdominal pain with valproate — exclude pancreatitis; stop drug and investigate
- Jaundice, severe hepatitis or coagulopathy — stop and escalate; do not rechallenge casually
- Full-speed lamotrigine titration while on valproate — SJS/TEN risk from raised lamotrigine levels
- Starting without pregnancy test, contraception plan, baseline LFT and FBC/platelets
Meet the patient
A 34-year-old man is brought in by police in acute mania — grandiose, assaultive, has not slept in four nights. He has a clear past response to valproate and cannot recall his lithium history. He is eating and drinking, his baseline liver panel and platelets are back, and the ward is asking what you want to do tonight.[1][11]
The exam question this vignette plants is precise: is this a patient valproate can be loaded in, and what must be true before you do? Pregnancy potential excluded, baselines done, oral intake confirmed, and the long-term maintenance question parked until the mania clears. This topic is the single-agent monograph behind that decision.[1][2][12]
References16ShowHide
- [1]Bowden CL, Brugger AM, Swann AC, et al. Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group JAMA, 1994.PMID 8120960
- [2]Geddes JR, Goodwin GM, Rendell J, et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial Lancet, 2010.PMID 20092882
- [3]Cipriani A, Barbui C, Salanti G, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis Lancet, 2011.PMID 21851976
- [4]Miura T, Noma H, Furukawa TA, et al. Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta-analysis Lancet Psychiatry, 2014.PMID 26360999
- [5]Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry Lancet Neurol, 2011.PMID 21652013
- [6]Tomson T, Battino D, Bonizzoni E, et al. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry Lancet Neurol, 2018.PMID 29680205
- [7]Meador KJ, Baker GA, Browning N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs N Engl J Med, 2009.PMID 19369666
- [8]Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study Lancet Neurol, 2013.PMID 23352199
- [9]Christensen J, Grønborg TK, Sørensen MJ, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism JAMA, 2013.PMID 23613074
- [10]Isojärvi JI, Laatikainen TJ, Pakarinen AJ, et al. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy N Engl J Med, 1993.PMID 8413434
- [11]Hirschfeld RM, Allen MH, McEvoy JP, et al. Safety and tolerability of oral loading divalproex sodium in acutely manic bipolar patients J Clin Psychiatry, 1999.PMID 10665626
- [12]Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder Bipolar Disord, 2018.PMID 29536616
- [13]Segura-Bruna N, Rodriguez-Campello A, Puente V, et al. Valproate-induced hyperammonemic encephalopathy Acta Neurol Scand, 2006.PMID 16774619
- [14]Allen MH, Hirschfeld RM, Wozniak PJ, et al. Linear relationship of valproate serum concentration to response and optimal serum levels for acute mania Am J Psychiatry, 2006.PMID 16449481
- [15]McElroy SL, Keck PE, Stanton SP, et al. A randomized comparison of divalproex oral loading versus haloperidol in the initial treatment of acute psychotic mania J Clin Psychiatry, 1996.PMID 8601548
- [16]Haymond J, Ensom MH Does valproic acid warrant therapeutic drug monitoring in bipolar affective disorder? Ther Drug Monit, 2010.PMID 19901867