[Valpromide, Valproic acid and removal of small intestine in the treatment of a chronic depression: a case report]

G Benjelloun, K Blandin, P Fossati
L'Encéphale 2004, 30 (4): 400-3
Valpromide (VPD) is an antiepileptic drug, derivative of Valproic acid (VPA), used as a mood-stabilizer in bipolar disorder for 25 years in several European countries. VPD is also used as an augmentation strategy in refractory depression. Despite chemical similarity between VPA and VPD, the pharmacokinetics of the 2 drugs in humans are quite distinct. We report a case of a patient, suffering from a bipolar treatment resistant depression, who dramatically improved after substituting VPD to VPA in association with fluoxetine. Mme X, 68 years old, has been hospitalized in March 2001 for the treatment of a resistant depression (TRD). She was suffering from removal of small intestine with chronic diarrhoea after a suicidal attempt two years ago. She had a bipolar disorder treated with VPD (1,200 mg/d) since 1 year. She presented a major depressive episode according to DSM IV with various symptoms like depressed mood, hypersomnia and difficulty initiating sleep, diminished ability to concentrate and to think, markedly diminished pleasure in all activities and major anxiety. Mme X fulfilled TRD diagnosis after resistance to two adequate antidepressants trials from different classes (clomipramine 175 mg/day and venlafaxine 300 mg/day). The antidepressant treatment (venlafaxine) was interrupted and she has been receiving a SSRI (fluoxetine 20 mg/day) for 4 weeks. After four weeks, she had a partial remission with persistent sleep problems, mood lability and anxiety. The VPA blood concentration was very low: 27 mg/L (normal range: 50 to 100 mg/L) in spite of a high dosage: 1,200 mg/day. Pharmacokinetic analysis of VPD shown that VPD transformation to VPA usually done in the intestine, was reduced because of the removal of hail intestine. We substituted VPD by VPA. Valproate blood concentration returned to normal range, induced dramatic improvement of depression within three days. VPD is an amide derivative of valproic acid (valproate), biotransformed by hydrolysis to its corresponding valproic acid. VPD is a prodrug of VPA. VPD is absorbed after transformation in gastro-intestinal mucous membrane. The adequate dosage of VPD (Depamide, 300 mg) is 4 to 6 tablets in acute manic phases, 2 to 4 tablets in long term treatment, 1 to 3 tablets in depressive episode. The biodisponibility of VPD is around 100% 75 and 90% of VPD is linked with protein albumin. The daily dosage determined the blood concentration of the active form (VPA), but this relation isn't linear. The optimal blood concentration of VPA (Depakine) ranges between 50 and 100 mg/L. the free form of VPA is influenced by protein disorders such as of hypoalbuminemia and by presence of fat acids in food. This case report demonstrates at a clinical level that VPD and VPA are not equivalent for treating bipolar depression. This case also suggests that a deep investigation of the pharmacokinetic of psychotropic drugs can help clinicians to resolve clinical problems of treatment of depression.

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