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* Lamotrigine generally has no significant effect on valproate levels, however caution is recommended.
* Start lamotrigine at low dose and check valproate plasma level after 1 week. Change valproate dose if necessary. <ref name=”medicatiebewaking”> Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002. </ref>
Very slow titration of lamotrigine is recommended, because lamotrigine-related skin rashes have been reported. <ref> {{Pubmed|16225978|Chang CC at al, Toxic epidermal necrolysis with combination lamotrigine and valproate in bipolar disorder. Prog Neuropsych. Biol Psychiatry. 2006 Jan;30(1):147-50}}</ref>
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* Very slow titration Valproic acid increases the blood level of lamotrigine is recommended because reports of the inhibition of glucuronidation. Adverse reactions, particularly skin rash, may occur with greater frequency or severity. Also other side effects may occur such as ataxia, tremor, sedation, and fatigue. However, such symptoms should improve as the dose of lamotrigine-related skin rashesis decreased. <refname="freeman"> {{Pubmed|162259789433333|Chang CC at Freeman et al, Toxic epidermal necrolysis with combination lamotrigine . Mood stabilizer Combinations: A Review of Safety and valproate in bipolar disorderEfficacy. Prog Neuropsych. Biol Am J Psychiatry. 2006 Jan1998;30(1)155:14712-5021}}</ref> * Also important, when lamotrigine is added to valproate therapy, valproate concentrations may be possibly decreased.<ref name="freeman"/>
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