Topiramate for Bipolar Disorders
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Question: What is the evidence that topiramte treats bipolar disorders?
Five open label, naturalistic case series’ of topiramate published:
| Study | Type /Dose (M=Mean) | N | M:F | Age | Subjects | Wks | Measure* | Response |
|---|---|---|---|---|---|---|---|---|
| McElroy | adjunctive 50-500mg/d | 54 | 3:7 | 42y | Outpatients, treatment refractory. Bipolar I (43), II (11), schizoaff (2). Divided by episode = manic (30), depressed (11), euthymic (13). | 4, 10, & last eval. (~30) | Change in CGI, YMRS, or IDS | Manic improved (YMRS 9.9 --> 5.3 --> 6.9, p 0.004). Depressives unchanged. Euthymics slightly more depressed (p 0.025). |
| Marcotte | adjunctive with a few monotherapy 200mg/d | 58 | 3:5 | 45y | Treatment refractory, inpatients (30%), outpatients (70%), bipolar (59%), cyclothym (17%) schizoaff (16%), numerous comorbidities. | 16 mean | Qualitative: mood, sleep, appetite, concentration. | 62% "marked/moderate improvement" |
| Calabrese | monotherapy 614mg/d | 11 | ? | ? | Hospitalized, severe treatment refractory acute mania | 4 | >50% YMRS | 27% improved |
| Kusumaker | adjunctive ? mg/d | 19 | 0:1 | ? | Out-patients, female, rapid cycling bipolar with psychotropic-induced wt gain. | ? | ? | 52% improved |
| Chengappa | adjunctive 1-300mg/d | 20 | ? | ? | Bipolar (18), schizoaff (2), manic episodes. | 12 | >50% on YMRS & CGI | 60% improved |
References:
Calabrese et al. Topiramate in severe treatment-refractory mania. Abstract, APA Toronto 6/1998.
Kusumaker et al. Topiramate in rapid cycling bipolar women. Abstract APA-Washington DC, 1999.
Abbreviations:
CGI (clinical global impression for mania), YMRS (Young mania rating scale), IDS (Inventory of depressive symptoms).
McElroy, Specific Strengths :
- Reported improvements maintained on 2 standard rating scales at 3 measurements.
- Subjects separated by mood at baseline.
McElroy, Specific Weaknesses:
- High drop out rate (35% @10wk, 52% total); these results were not counted except in the "last evaluation" category. Another 13% were not counted because additional psychotropics were added when their mood worsened.
- Initial YMRS was relatively low (9.9). Subsets with higher YMRS were also analyzed (similar results found).
Marcotte, Specific Strengths:
- None
Marcotte, Specific Weaknesses:
- Qualitative measures done in clinical, not research setting. Bias/placebo-effect is evident in his statement that "majority of responders showed improvement within 72 hours at dose of 50mg/d." In comparison, McElroy found a "slow response" with similar dosages.
- Chart review. Drop-outs not applicable (though 10% discontinued due to SE).
- Subjects had high mix of conditions, which led to much categorizing (data-fishing) with unimpressive results.
Generalizations:
- Five case series were found for topiramte in bipolar disorders, all except one were for adjunctive therapy.
- Of the two larger studies, one had severe methodologic limitations (Marcotte); the other (McElroy) more rigorous study showed good results for mania but was limited by a high drop out rate.
- No studies could control for clinician/patient bias, placebo effect, natural course of illness, and effect of other drugs.
- Most studies used refractory patients
- No studies had clean exclusion/inclusion criteria.
Presented by Chris Aiken, M.D.
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