RESUMO
OBJECTIVE: To compare the efficacy and safety of carbamazepine extended-release capsules (CBZ-ERC) administered twice daily (BID) versus once daily for the treatment of manic symptoms associated with bipolar I disorder in adults. DESIGN: This was a Phase IIIb, randomized, double-blind, parallel-group, multicenter, 12-week study. Subjects were randomized (1:1) to CBZ-ERC once daily at bedtime (QHS) or BID. Dosing was initiated at CBZ-ERC 200mg/d and titrated to achieve an optimal dose (target dose, 800mg/d; maximum dose, 1600mg/d). The primary efficacy outcome variable was the Young Mania Rating Scale (YMRS). The Hamilton Rating Scale for Depression, 21-item version (HAM-D(21)), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions Scale-Bipolar Version (CGI-BP), and time to remission were secondary outcome variables. Safety measures included recording of adverse events, physical examination, vital signs (blood pressure, pulse rate, and weight), and clinical laboratory and electrocardiogram (ECG) parameters. RESULTS: BID and QHS dosing were equally effective in improving symptoms of bipolar disorder, as measured with the YMRS, HAM-D(21), MADRS, and CGI-BP. Both BID and QHS dosing significantly improved total scores on the YMRS, HAM-D(21), and MADRS at all time points without statistically significant differences between groups. All three components of the CGI-BP improved during the study, and a large percentage of subjects in both groups achieved remission without significant differences between groups. Both CBZ-ERC regimens appeared to be safe and well tolerated. CONCLUSION: These results suggest QHS dosing may be a safe and effective alternative to BID dosing of CBZ-ERC for treating manic episodes for many adults with bipolar I disorder, although additional studies are needed to confirm this finding.
RESUMO
OBJECTIVE: To evaluate the safety and efficacy of carbamazepine extended-release capsules (CBZ-ERC) in combination with other psychotropic medications for the treatment of bipolar I disorder. DESIGN: In this Phase IIIb, open-label, eight-week, observational, polypharmacy study, adult subjects were started on CBZ-ERC 200mg and titrated over four weeks to optimal dose (1600mg/d maximum). Concomitant lithium and atypical antipsychotics (olanzapine, risperidone, quetiapine, aripiprazole) were permitted. Safety assessments included adverse events, laboratory parameters, physical examination, medication history, vital signs, and electrocardiogram. Efficacy measures included the Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impressions Scale-Bipolar Version (CGI-BP). All data were summarized using descriptive statistics. RESULTS: Overall, 45 (84.9%) subjects reported treatment-emergent adverse events (TEAEs); most were mild or moderate in severity. The most commonly reported TEAEs were somnolence (n=14, 26.4%), sedation (n=12, 22.6%), dizziness (n=11, 20.8%), headache (n=9, 17.0%), and nausea (n=7, 13.2%). There were no clinically significant changes in vital signs, including weight. Mean changes in laboratory parameters were small, with values that were within the normal range for the majority of subjects. Few changes relative to screening for other safety parameters occurred. Mean total YMRS score decreased from baseline at each study visit. HAM-D and MADRS scores decreased from baseline at Weeks 4 and 8, and all three CGI-BP components (overall bipolar disorder, mania, and depression) improved during the study. CONCLUSION: CBZ-ERC appears to be safe and effective for use in combination with atypical antipsychotics and lithium for treatment of bipolar I disorder.
RESUMO
Carbamazepine (CBZ) has a long history of successful use in epilepsy and, therefore, has a safety profile that is well characterised. Additionally, an extended-release formulation of CBZ (CBZ-ERC; Equetro, Shire US) has recently been approved for use in bipolar disorder. The most frequent adverse events associated with CBZ are somnolence, fatigue, dizziness and headache. Rash and leukopoenia may occur in approximately 10% of patients, but are benign and transient in most cases. Rare serious adverse effects include agranulocytosis, aplastic anaemia, Stevens-Johnson syndrome and toxic epidermal necrolysis. Although changes in lipid profiles have been noted, hyperglycaemia does not occur with CBZ, and clinically significant weight gain is uncommon. Proper monitoring and careful titration of the extended-release formulation should allow for successful use of CBZ in psychiatric patients.
