Our previous study has shown the beneficial effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as adjunctive therapy with carbamazepine (CBZ) in the 12-week treatment of bipolar disorders (Zhang ZJ, Kang WH, Tan QR, Li Q, Gao CG, Zhang FG, et al., Adjunctive herbal medicine with carbamazepine for bipolar disorders: a double-blind, randomized, placebo-controlled study. J Psychiatr Res; 2005). Here, we present follow-up data obtained from a continuation of the previously reported study. Treatment and clinical evaluation of bipolar patients (n = 188) who had randomly received 12-week CBZ plus placebo (n = 92) or CBZ plus FEWP (n = 96) were extended to 26 weeks under double-blind condition. Patients in adjunctive FEWP showed a significantly lower overall discontinuation rate (31%) at endpoint compared to placebo (51%, p = 0.009), and of 15% in adjunctive FEWP discontinued due to intolerable side effects, markedly lower than those in placebo (28%, p = 0.019). No difference in discontinuation for lack of efficacy and exacerbation was observed in the two groups. Patients receiving adjunctive FEWP had significantly fewer adverse side effects and lower serum levels of CBZ than those in placebo. A separate study was further conducted to evaluate the effectiveness of FEWP as monotherapy in depressed patients. A total of 87 unipolar and 62 bipolar depressed patients were randomly assigned to treatment with 36 g/day FEWP (n = 86) or placebo (n = 63) for 12 weeks under double-blind condition. Efficacy was measured using the Hamilton Rating Scale for Depression (HAMD), Montgomery–Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Severity (CGI-S). Both unipolar and bipolar patients assigned to FEWP displayed significantly greater improvement on the three efficacy indices and significantly higher clinical response rate (74%) than those treated with placebo (42%, p < 0.001) at endpoint. These results suggest that adjunctive FEWP improves tolerability of CBZ in the long-term use, which may be associated with the suppression of blood CBZ concentrations via herb-drug interactions. FEWP monotherapy may be also an effective alternative treatment for depressed conditions.