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Objectives: About 50% of patients with unipolar depression suffer from treatment-resistant depression (TRD). Animal studies have suggested potential antidepressant properties of valproate (VPA) possibly due to its implication in epigenetic programming.Methods: Fourteen TRD patients (seven males and seven females; age 19–59) received VPA (375–1000 mg/day) in addition to their treatment regimen after previously failing to respond to two or more antidepressant trials and/or different combinations. Clinical response to VPA was investigated prior the treatment (T-0) and after 1 (T-1), 4 (T-4) and 7 (T-7) months of therapy using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI).Results: Compared to T-0, VPA significantly decreased MADRS score at T-1 (P < 0.001), T-4 (P < 0.001) and T-7 (P < 0.001) (partial η2=0.86). Importantly, MADRS score at T-7 (13.6 ± 1.6, mean ± SEM) was closer to the reported value of remission (MADRS <10), and none of the patients relapsed during the observational period. Compared to T-0, VPA also decreased CGI-Severity of illness score at T-1 (p = 0.03), T-4 (p < 0.001) and T-7 (p < 0.001) (partial η2 = 0.74).Conclusions: Antidepressant augmentation with VPA provided substantial clinical improvement and maintenance over a relatively long-term period in a subgroup of patients with severe TRD. VPA thus deserves further exploration in large double-blind clinical trials. [ABSTRACT FROM PUBLISHER]

Abstract: Acute tryptophan depletion (ATD) in currently depressed patients has no immediate effect on symptoms, but leads to transient symptom improvement or worsening the next day. In view of recent findings concerning the cognitive effects of serotonin manipulations, we used ATD in fourteen depressed patients to investigate whether cognitive effects following ATD predict symptom changes. We found that symptom improvement 24h after ATD was associated with an improved recall of positive words and with less attentional bias and recall of negative words, 5h after ATD. These results indicate that serotonergic alterations affect emotional processing which may subsequently lead to symptom changes. [Copyright &y& Elsevier]

Depressive disorders are associated with various cognitive impairments. Studies on whether or not these impairments persist into the euthymic phase have shown conflicting results, due to differences in test versions and in study samples. In this paper, we aimed to compare the cognitive performance of remitted depressed patients with that of age- and gender-matched healthy volunteers across a wide range of cognitive domains. In two studies, we found few differences on neutral as well as emotional information processing tests. The findings indicate that remitted depressed patients who use antidepressant medication still show an increased recognition of facial expression of fear compared to healthy controls. Patients also performed worse on a test of recognition of abstract visual information from long-term memory. No other residual cognitive impairments were found. These results indicate that most of the cognitive impairments associated with depression resolve with recovery through medication, even when recovery is incomplete. Considering the finding that remitted depressed patients have higher levels of cognitive reactivity, future studies may investigate the possibility that these cognitive impairments have not resolved but have become latent, and may therefore easily be triggered by small changes in mood state. Depression and Anxiety 0:1–10, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]