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V alproate (valproic acid), a well-established anticonvulsant, is principally effective in bipolar disorder. [1][2][3][4] In addition, valproate has been used for the management of a range of psychiatric conditions, such as schizophrenia, personality disorder, anxiety, and agitation in dementia. [4][5][6] The need for therapeutic drug monitoring of valproate in the treatment of epilepsy has been demonstrated. A plasma trough concentration exceeding 50 mg/L is advised in order to reach therapeutic effects on epilepsy, and trough levels exceeding 100-120 mg/L are associated with toxicity and occurrence of adverse events. [6][7][8][9][10][11] There is no clear concentration-response relationship for valproate in most psychiatric conditions. However, the range recommended in the literature for acute mania is 45-125 mg/L in adult patients and 65-90 mg/L in older patients; in maintenance therapy, blood levels of 55-115 mg/L have been recommended. [12][13][14][15] For this report, we used the ranges advised by our national guidelines 16 : 60-80 mg/L in maintenance therapy and 80-120 mg/L in acute episodes.We present a case in which signs of valproate intoxication were clinically present, although the valproate trough concentrations were considered therapeutic (60-120 mg/L).Case report. Ms A, a 78-year-old woman, was admitted to a geriatric psychiatry ward because of psychosis with manic features. The patient's psychiatric history revealed schizoaffective disorder (DSM-5 criteria), and her somatic history included a stroke, metabolic syndrome, and chronic renal insufficiency. Psychiatric examination showed high speed in thinking, delusions, command auditory hallucinations, and a euphoric mood. Physical examination showed no abnormalities besides obesity and hyperkinesia due to haloperidol. Laboratory tests showed chronic renal insufficiency (clearance of 59 mL/min/1.73 m 2 [reference > 90 mL/min/1.73 m 2 ]).Prescription of lithium carbonate was not the first choice due to lack of efficacy in the past and side effects (tremor and decline of renal function) in combination with the current reduced renal function. Ms A's manic psychosis was treated with valproate and haloperidol. Valproate was dosed according to the patient's body weight in a ratio of 20 mg/kg, which resulted in a daily dosage of 2,100 mg.Two weeks later, she developed a fluctuating mental status with complaints of sedation, vertigo, and insecurity in walking with falling. Physical examination revealed no new abnormalities, and laboratory tests showed a serum albumin level of 26 g/L (reference, 35-50 g/L) and a plasma trough concentration of 91.9 mg/L (reference, 60-120 mg/L). In medication review by the pharmacist, a free protein unbound trough concentration level of valproate was determined at 34.7 mg/L (reference, 4-12 mg/L). Adjusting the daily valproate dosage to 600 mg resulted in a total valproate level of 49.9 mg/L and a free concentration of 6

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ObjectivesThe association between depression and metabolic syndrome is becoming more obvious.AimsWe examined the relationship between the number and individual components of metabolic syndrome and late-life depressive symptom clusters.MethodsIn 1279 individuals aged 50 through 70 participating in the Nijmegen Biomedical Study (Cross-sectional populationbased survey), we measured all metabolic syndrome components and depressive symptoms using the Beck Depression Inventory (BDI). Principal components analysis of BDI-items yielded two factors, representing a cognitive-affective and a somatic-affective symptom-cluster. Multiple regression analyses adjusted for confounders were conducted with BDI sum score and both depression symptom-clusters as dependent variables, respectively. We explored the differences in this association between men and women.ResultsIn fully adjusted models, both presence of the metabolic syndrome as well as number of components was associated with the BDI sumscore(resp. β=0.063;p=0.022 vs. β=0.112;p< 0.001), the latter showing the strongest association. These associations were primarily driven by the somatic-affective symptom-cluster. Testing individual components of the metabolic syndrome, showed that in men waist circumference, triglycerides and HDL cholesterol were significantly associated with depression, whereas in women only the waist circumference.ConclusionsThe specific association somatic-affective symptoms suggest confounding by a (subclinical) somatic condition in stead of a real association with classical depression. The identified sex-differences suggest different pathways between depression and metabolic perturbations in men only. However, as vascular disease develops at higher ages in women and findings were in the same direction but non-significant in women, future research in older women sample should confirm our findings.