Evidence for transmission disequilibrium at the DAOA gene locus in a schizophrenia family sample.

Recently, the DAOA gene locus on chromosome 13q32-q34 has been implicated in the etiology of schizophrenia. We genotyped three single-nucleotide polymorphisms (SNPs: rs778294, rs779293 and rs3918342) in this region in 126 Chinese family trios. In this study, we have identified statistically significant transmission disequilibrium in two markers rs778293 (P=0.01) and rs3918342 (P=0.02), and a highly significant under-transmission between haplotype CAT (P=0.0005) and schizophrenia. The results provide further evidence to support that DAOA gene locus is involved in conferring susceptibility to schizophrenia.

The effectiveness of carbamazepine in unipolar depression: a double-blind, randomized, placebo-controlled study.

Our previous studies have shown the effectiveness of carbamazepine (CBZ) in the treatment of bipolar depression. This double-blind, randomized, placebo-controlled study was designed to further evaluate the efficacy of CBZ in unipolar depressed subjects who never received antidepressant and other psychotherapeutic treatment. A total of 89 patients who had at least two major depressive episodes, but never experienced mania or hypomania, were randomly assigned to treatment with immediate-release CBZ 300-800 mg/daily (n=51) or placebo (n=38) for 12 weeks. The primary efficacy was measured using the Hamilton Rating Scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Severity (CGI-S). The mean final CBZ dose of CBZ-treated patients was 461.6 mg/day. CBZ treatment yielded significantly greater improvements on the three efficacy measures at week 8 through endpoint compared to placebo. Patients assigned to CBZ treatment also had a significantly higher clinical response rate than placebo (74% vs. 42%, p<0.001), as defined for > or = 50% reduction in HAMD score. Based on the results of our present and previous studies, we suggest that CBZ might be considered an alternative in the management of certain conditions in major depressive disorder.

The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP) for mood disorders: double-blind, placebo-controlled studies.

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.

Adjunctive herbal medicine with carbamazepine for bipolar disorders: A double-blind, randomized, placebo-controlled study.

Chinese herbal medicines possess the therapeutic potential for mood disorders. This double-blind, randomized, placebo-controlled study was designed to evaluate the efficacy and side effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as an adjunct to carbamazepine (CBZ) in patients with bipolar disorders. One hundred and twenty-four bipolar depressed and 111 manic patients were randomized to treatment with CBZ alone, CBZ plus FEWP, or equivalent placebo for 12 weeks. CBZ was initiated at 300mg/day and FEWP was given at a fixed dose of 36g/day. Efficacy measures included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale , Young Mania Rating Scale, Bech-Rafaelsen Mania Scale, and Clinical Global Impression-Severity (CGI-S). CBZ monotherapy produced significantly greater improvement on manic measures at week 2 through endpoint and CGI-S of depression at endpoint compared to placebo. CBZ monotherapy also yielded significantly higher clinical response rates than placebo on bipolar depression (63.8% vs. 34.8%, p=0.044) and mania (87.8% vs. 57.1%, p=0.012). Compared to CBZ monotherapy, adjunctive FEWP with CBZ resulted in significantly better outcomes on the three measures of depression at week 4 and week 8 and significantly greater clinical response rate in depressed subjects (84.8% vs. 63.8%, p=0.032), but failed to produce significantly greater improvement on manic measures and the response rate in manic subjects. There was a lesser incidence of dizziness and fatigue in the combination therapy compared to CBZ monotherapy. These results suggest that adjunctive FEWP has additive beneficial effects in bipolar patients, particularly for those in depressive phase.

Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Previous studies suggest that the serotonin-3 (5-HT3) receptor antagonist ondansetron possesses the therapeutic potential for schizophrenia. This study was designed to determine whether ondansetron as an adjunct to haloperidol could enhance the clinical efficacy and reduce the adverse side effects in chronic treatment-resistant schizophrenia. METHODS: Under double-blind, randomized conditions, 121 treatment-resistant inpatients with chronic DSM-IV-diagnosed schizophrenia received haloperidol (4-30 mg/day) combined with either placebo (N=63) or a fixed dose of 8 mg/day of ondansetron (N=58) for 12 weeks. Efficacy was defined as the change from baseline to endpoint in score on overall scale and subscales of the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). Side effects were evaluated using the Treatment Emergent Symptom Scale and Extrapyramidal Symptom Rating Scale. RESULTS: Ondansetron combined with haloperidol produced a significantly greater improvement on PANSS overall scale and subscales for negative symptoms, general psychopathology, and cognition at endpoint compared to placebo with haloperidol, but no between-treatment group difference was observed on the subscale for positive symptoms and CGI-S. The ondansetron-treated group had a significantly higher proportion of patients with a 30% or greater baseline-to-endpoint reduction in PANSS total score than placebo. Patients in adjunctive ondansetron therapy also experienced significantly lower incidence and severity of parkinsonism and akathisia as well as fewer behavioral hyperactivity, cardiac, and gastrointestinal side effects. CONCLUSIONS: Ondansetron is an effective adjunctive agent in enhancing the effectiveness and reducing some adverse side effects of antipsychotic therapy for chronic, treatment-resistant schizophrenia, particularly for negative and cognitive symptoms.

Differences in hypothyroidism between lithium-free and -treated patients with bipolar disorders.

The majority of the previous studies of thyroid abnormalities in bipolar patients was conducted in populations containing various proportions of lithium-treated subjects. In the present study, we sought to determine whether there exist differences in hypothyroid profile between lithium-free and -treated bipolar patients. Bipolar patients never treated with lithium and carbamazepine (n=78) and those currently in lithium therapy (n=53) were included in this study. Serum concentrations of total thyroxine (T(4)), total triiodothyronine (T(3)), and thyroid-stimulating hormone (TSH) were compared between lithium-free and -treated patients. The rate of hypothyroidism in lithium-free patients was significantly lower than those treated with lithium (6.3%-10.8% vs. 28.0%-32.1%). Significant changes in the three thyroid indices indicative of hypothyroidism were consistently associated with longer illness duration in lithium-free manic patients, but with greater severity of mania and more mood episodes in their lithium-treated counterparts. In lithium-free depressed patients, more episodes were associated with lower T(4) levels; whereas in their lithium-treated counterparts, longer illness duration was associated with higher TSH levels and females with lower T(3) levels. These results suggest that bipolar patients with and without lithium exposure differ in prevalence and association of hypothyroidism and may have different response to thyroid hormone therapy.