Effectiveness of Adjunctive Gabapentin in Resistant Bipolar Disorder: Is It Due to Anxious-Alcohol Abuse Comorbidity?

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Abstract
We evaluated effectiveness and predictors of response of gabapentin (GBP) as adjunctive treatment in a sample of 43 subjects with DSM-III-R bipolar disorder who were resistant to standard mood stabilizers. Diagnostic evaluation was performed by means of the Semistructured Interview for Mood Disorder. Clinical evaluation was performed at the beginning and end of the observation period by means of the Hamilton Rating Scale for Depression (HAM-D), the Young Mania Rating Scale, and the Clinical Global Impression Scale. GBP was administered as an adjunctive treatment for an 8-week period in combination with other mood stabilizers, benzodiazepines, antidepressants, and neuroleptics. Mean dosage +/- SD at week 8 was 1270 +/- 561.4 mg (range, 600-2400 mg). Adjunctive treatment with GBP was well tolerated by almost all the subjects; only three patients had to interrupt treatment before week 8, two because of inefficacy and one because of the appearance of side effects (ataxia and irritability); in other patients, the most frequent side effects were sedation, irritability, tremor, ataxia or motor instability, and nausea. Eighteen (41.9%) of 43 patients who began treatment were considered responders. Mean total HAM-D score showed a significant reduction during the 8 weeks of treatment. Analysis of the various HAM-D dimensions showed that the anxiety-somatization factor was the one with the greatest change. Seventeen of the 18 responder patients remained in remission for a period ranging from 4 to 12 months without clinically significant side effects or adverse events. One patient had to interrupt GBP treatment and be administered neuroleptics because of the reappearance of manic symptoms. Regarding response predictors, logistical regression analysis showed that the presence of panic disorder and alcohol abuse was associated with positive response. The results of the present study replicate prior studies indicating that GBP is an effective and well tolerated treatment in a large proportion of bipolar patients who are resistant to traditional mood stabilizers. More specifically, this drug appears to have antidepressant and anxiolytic properties. What is new in the present report is the suggestion that the utility of GBP in resistant bipolar disorder resides in its effectiveness against comorbid panic disorder and alcohol abuse.

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