ABSTRACT
BACKGROUND: Divalproex extended-release (divalproex-ER) is effective in acute mania, and limited data suggest divalproex may have efficacy in acute bipolar depression. METHODS: A 7-week, open-label trial of divalproex-ER monotherapy or adjunctive therapy was conducted in 28 outpatients (15 female, mean age 36.7+/-9.1, and mean duration of illness 22.1+/-11.1 years) with bipolar II depression (39% with rapid cycling course of illness within the prior year). Divalproex-ER was generally given as a single dose at bedtime, starting at 250mg and increased by 250mg every 4 days to symptom relief or adverse effects. Efficacy was assessed using weekly prospective Montgomery Asberg Depression Rating Scale (MADRS) scores. RESULTS: Overall, mean divalproex-ER final doses and serum concentrations were 1469mg/day and 80.1microg/mL, respectively. Mean MADRS scores (last observation carried forward) decreased significantly from baseline in patients in the overall group (from 30.1 to 15.2, p<.00001). The overall response rate was 54%. Divalproex-ER therapy was generally well tolerated, with no early discontinuations due to adverse events. LIMITATIONS: This study is limited by a small sample size and an open-label study design with no placebo control. CONCLUSIONS: Divalproex-ER as monotherapy and adjunctive therapy was well tolerated and yielded an overall response rate of 54% in bipolar II depression. Based on the results of this pilot study, randomized, double-blind, placebo-controlled studies of divalproex-ER in bipolar II depression are warranted.
Subject(s)
Anticonvulsants/administration & dosage , Bipolar Disorder/drug therapy , Valproic Acid/administration & dosage , Acute Disease , Adult , Anticonvulsants/adverse effects , Anticonvulsants/pharmacokinetics , Bipolar Disorder/blood , Delayed-Action Preparations , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Treatment Outcome , Valproic Acid/adverse effects , Valproic Acid/pharmacokineticsABSTRACT
OBJECTIVE: To assess new treatment options for bipolar disorders. METHOD: Controlled studies of new treatments for bipolar disorders were identified by computerized searches and reviews of scientific meeting proceedings, and were compiled by drug category. RESULTS: Two main categories of medications, newer anticonvulsants and newer antipsychotics, are yielding emerging new treatment options for bipolar disorders. Newer anticonvulsants have diverse psychotropic profiles, and although not generally effective for acute mania, may have utility for other aspects of bipolar disorders (e.g. lamotrigine for maintenance or acute bipolar depression), or for comorbid conditions (e.g. gabapentin for anxiety or pain, topiramate for obesity, bulimia, alcohol dependence, or migraine, and zonisamide for obesity). In contrast, newer antipsychotics generally appear effective for acute mania, and some may ultimately prove effective in acute depression (e.g. olanzapine combined with fluoxetine, quetiapine) and maintenance (e.g. olanzapine). CONCLUSION: Emerging research is yielding new treatment options for bipolar disorders and comorbid conditions.
Subject(s)
Anticonvulsants/therapeutic use , Antipsychotic Agents/therapeutic use , Bipolar Disorder/drug therapy , Drug Tolerance , HumansABSTRACT
The antidepressive effect of Hydiphen was evaluated and compared with imipramine in patients with endogenous depression. The Hydiphen group consisted of 23, and imipramine group of 22 subjects. The evaluation was made using psychometric scales, orthostatic test, ecg, and laboratory tests before treatment as well as during and after the clinical trial. The results proved the antidepressive effect of Hydiphen, in particular its influence on psychomotor activity, and on both mood and anxiety. In comparison to imipramine Hydiphen's++' influence on vegetative symptoms was less pronounced and the drug showed less cardiotoxicity.
Subject(s)
Clomipramine/therapeutic use , Depressive Disorder/drug therapy , Adult , Clinical Trials as Topic , Depressive Disorder/psychology , Female , Humans , Imipramine/therapeutic use , Male , Middle Aged , Psychiatric Status Rating ScalesABSTRACT
The active cation transport mechanisms (ouabain-dependent fluxes of sodium; ODS) and potassium (ODK), sodium-potassium adenosine triphosphatase ([Na+-K+]-ATPase) activity as well as lithium-sodium countertransport (LSC) reflecting sodium exchange diffusion, were studied in erythrocytes of forty-four patients with endogenous depression both in acute episode and in remission, and compared with thirty healthy control subjects. During depressive episodes, the activities of all mechanisms studied were significantly lower than those of control subjects. In female depressives the values of ODS and LSC were lower than in males. In remission, the activity of all mechanisms rose, reaching in most patients the values of control subjects. In female patients, activities of ODS and LSC were still lower than in male patients and female controls. The activities of ODS and LSC had the highest discriminating power between depressive patients and control subjects. It appears that membrane pathology may be an aetiologic factor in endogenous depression. A disturbance in erythrocyte transport presents most conspicuously during depressive episodes and in some patients may also persist to the normothymic period.