Factors Associated with Doses of Mood Stabilizers in Real-world Outpatients with Bipolar Disorder

Objective@#Several evidence-based practice guidelines have been developed to better treat bipolar disorder. However, the articles cited in these guidelines were based on clinical or basic studies with specific conditional settings and were not sufficiently based on real-world clinical practice. In particular, there was little information on the doses of mood stabilizers. @*Methods@#The MUlticenter treatment SUrvey on BIpolar disorder in Japanese psychiatric clinics (MUSUBI) is a study conducted to accumulate evidence on the real-world practical treatment of bipolar disorder. The questionnaire included patient characteristics such as comorbidities, mental status, treatment period, Global Assessment of Functioning (GAF) score, and details of pharmacological treatment. @*Results@#Most patients received mood stabilizers such as lithium (n = 1,317), valproic acid (n = 808), carbamazepine (n = 136), and lamotrigine (n = 665). The dose of lithium was correlated with age, body weight, number of episodes, depression and GAF. The dose of valproic acid was correlated with body weight, number of episodes, presence of a rapid cycle and GAF. The dose of carbamazepine was correlated with age, mania, and the presence of a rapid cycle. The dose of lamotrigine was correlated with the number of episodes, depression, mania, psychotic features, and the presence of a rapid cycle. Doses of coadministered mood stabilizers were significantly correlated, except for the combination of valproic acid and lamotrigine. @*Conclusion@#The dose of mood stabilizers was selectively administered based on several factors, such as age, body composition, current mood status and functioning. Further prospective studies are required to confirm these findings.

Duloxetine, a Selective Noradrenaline Reuptake Inhibitor, Increased Plasma Levels of 3-Methoxy-4-hydroxyphenylglycol but Not Homovanillic Acid in Patients with Major Depressive Disorder

OBJECTIVE: We investigated the effects of duloxetine on the plasma levels of catecholamine metabolites and serum brain-derived neurotrophic factor (BDNF) in 64 patients with major depressive disorder (MDD). METHODS: Major depressive episode was diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) according to the DSM-IV text revision (DSM-IV-TR) criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17). Blood sampling and clinical evaluation were performed on days 0, 28, and 56. RESULTS: Duloxetine treatment for 8 weeks significantly increased the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels but not the homovanillic acid (HVA) levels in responders with MDD. CONCLUSION: These results imply that noradrenaline plays an important role in alleviating depressive symptoms.

Serum Levels of Brain-Derived Neurotrophic Factor at 4 Weeks and Response to Treatment with SSRIs

OBJECTIVE: It is important to predict a response to an antidepressant in early time after starting the antidepressant. We previously reported that serum brain-derived neurotrophic factor (BDNF) levels in responders to treatment with antidepressants were increased, whereas, those in nonresponders were not. Therefore, we hypothesized that the changes in serum levels of BDNF from baseline (T0) to 4 weeks (T4) after treatment with selective serotonin reuptake inhibitors (SSRIs) predict the response to the treatment at 8 weeks (T8) in depressed patients. To confirm the hypothesis, we measured serum BDNF at T0, T4, and T8 during the treatment with SSRIs (paroxetine, sertraline, and fluvoxamine). METHODS: One hundred fifty patients (M/F; 51/99, age; 50.4+/-15.1 years) met major depressive disorder (MDD) using by DSM-IV-TR enrolled in the present study. We measured serum BDNF concentrations at T0, T4, and T8 in patients with MDD treated with SSRIs. RESULTS: The changes in serum BDNF, age, sex, dose of SSRIs, and HAMD-17 score did not predict the response to SSRIs at T8. CONCLUSION: These results suggest that the changes in serum BDNF levels from T0 to T4 could not predict the subsequent responses to SSRIs at T8.

Follow-up Study on Electroconvulsive Therapy in Treatment-resistant Depressed Patients after Remission: A Chart Review

OBJECTIVE: Electroconvulsive therapy (ECT) has proven to be effective in treatment-resistant depression (TRD). In recent reports, 70% to 90% of patients with TRD responded to ECT. However, post-ECT relapse is a significant problem. There are no studies investigating risk factors associated with reintroducing ECT in depressive patients after remission previously achieved with former ECT. The aim of the present study is to examine such risk factors using a sample of TRD patients. METHODS: We conducted a chart review to examine patient outcomes and adverse events over short- and long-term periods. Forty-two patients met the criteria for major depressive disorder. RESULTS: The response rate was 85.7% (36/42). There were no significant differences in the baseline characteristics of patients exhibiting remission, response or non-response. The rate of adverse events was 21.4% (9/42). Among 34 patients who were available for follow-up, 18 patients relapsed (relapse rate, 52.9%), and 6 patients were reintroduced to ECT. The patients' age and age of onset were significantly higher in the re-ECT group than non re-ECT group. CONCLUSION: Our results suggest that older age and older age of onset might be considered for requirement of re-ECT after remission previously achieved with former ECT.

No Association between the Response to the Addition of an Atypical Antipsychotic Drug to an Selective Serotonin Reuptake Inhibitor or Serotonin Norepinephrine Reuptake Inhibitor and the Brain-Derived Neurotrophic Factor (Val66Met) Polymorphism in Refracto

OBJECTIVE: This study examined the association between the brain-derived neurotrophic factor (BDNF) (Val66Met) polymorphism and the response to the addition of an atypical antipsychotic drug to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in treatment-refractory depression. METHODS: The study enrolled 64 patients meeting the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depressive disorder who were treated with at least two courses of a single antidepressant, but who had Hamilton Depression Rating Scale (HAMD-17) scores > or =15 points that were reduced less than 50% over at least a 4-week treatment period. There were 24 males and 40 females (age range 27-68 years; mean+/-SD, 48+/-13 years). The patients' clinical improvement was evaluated using the HAMD-17. Patients with at least a 50% decrease in the HAMD-17 score were defined as responders. Serum BDNF levels were assayed using enzyme-linked immunosorbent assays and the presence of the BDNF (Val66Met) polymorphism was determined using the TaqMan genotyping assay. RESULTS: No correlation was found between the BDNF (Val66Met) polymorphism and a positive response to adding an atypical antipsychotic drug. No differences were observed in the changes in the serum BDNF levels and HAMD-17 scores between Val66Val and Met-carriers. In addition, in patients who experienced remission, the atypical antipsychotic drug was discontinued after at least 3 months of treatment and the patients were then followed for 1 year; 14 of 27 patients (52%) relapsed within 1 year. CONCLUSION: These results suggest that the BDNF (Val66Met) polymorphism is not associated with the response to the augmentation of a SSRI or SNRI with an atypical antipsychotic drug, and that the combination of an atypical antipsychotic drug and a SSRI or SNRI should be continued for 3 months or more in refractory depressed patients in the Japanese population.