Clonazepam augmentation of antidepressants: does it distinguish unipolar
from bipolar depression
BACKGROUND: The authors compared the effect of clonazepam supplement treatment on
unipolar depression and bipolar depression. METHODS: A total of 38 protracted depression
patients with unipolar depression (n = 19) or bipolar depression (n = 19) were treated with 3.0 mg
clonazepam for 4 weeks. RESULTS: In the unipolar depression group, 84.2% of the subjects
fulfilled the response criteria (at least an 80% reduction in their HDRS score). However, in the
bipolar depression group, only 10.5% of them fulfilled these criteria. CONCLUSIONS: The
difference in responses between the two groups supposes that the underlying abnormality in
unipolar depression is not the same as that in bipolar depression. This trial also supposed that
clonazepam can play active role in the treatment of protracted depression in patients with unipolar
depression. LIMITATIONS: This finding was made in an open study, and the effect on clonazepam
alone was not established.
Use of topiramate in treatment-resistant bipolar spectrum disorders.
To evaluate the effectiveness and safety of topiramate as add-on, long-term therapy for
treatment-resistant bipolar-spectrum disorders, 34 DSM-IV bipolar-spectrum patients, including
bipolar I (n = 28), bipolar II (n = 3), bipolar not otherwise specified (n = 2), and schizoaffective
disorder bipolar type (n = 1), considered to be resistant to treatment with lithium, carbamazepine,
and valproate, received increasing doses of topiramate as adjunctive therapy for their manic (n =
17), depressive (n = 11), hypomanic (n = 3), or mixed (n = 3) symptoms. Outcome measures
included the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression
(HAM-D), and the Clinical Global Impression (CGI) for Severity. Patients were followed up for 6
months. Twenty-five patients (74%) completed the 6-month follow-up. Nine patients (26%)
dropped out early due to lost of follow-up (n = 4), worsening of symptoms (n = 2), side effects (n =
1), hospitalization due to intercurrent illness (n = 1), and noncompliance (n = 1). By intent-to-treat
analysis, there was a significant reduction in YMRS, HAM-D, and CGI scores (p < 0.0001 for all
measures at the endpoint) after the introduction of topiramate. Most therapeutic effects appeared
between weeks 2 and 6. Fifty-nine percent of manic patients and 55% of depressed patients were
considered to be responders to the drug, which was well tolerated; only one patient discontinued
due to side effects. The most common side effect was paraesthesia (n = 2). Ten patients
experienced moderate weight loss during the follow-up period. The mean topiramate dose at
endpoint was 202 +/- 65 mg/day. These preliminary results indicate that adjunctive topiramate may
be useful in the long-term treatment of bipolar spectrum disorders, even in the most difficult-to-treat
patients.