 The design was a randomized, double-blind, placebo controlled clinical trial of 12 weeks of adjunctive treatment with N-acetyl-cysteine NAC, 1800mgday. Participants will be patients with bipolar disorders with and without TUD, they will allocated to one of two groups at random to receive NAC or placebo For the evaluation of oxidative stress biomarkers will be assess among others malondialdehyde MDA, lipid hydroperoxide,nitric oxide metabolites NOx, antioxidant potential total plasma TRAP, advanced oxidation protein products AOPP, superoxide dismutase SOD, catalase, the total glutathione GSH and oxidized GSSG, paraoxonase PON 1 activity thiol group SH-group.For the evaluation of inflammation biomarkers will be analyze : BDNF, GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 p70, IL-13, IL-15, IL-17, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6,IL-6R, IL-7, IL-8, Leptin, TNF-α, TNF-RI, TNF-RII, high-sensitivity C-reactive protein hs-CRP, erythrocytes sedimentation rate ESR, homocysteine, haptoglobin, albumin , uric acid and fibrinogen. 