Of 26 subjects screened, 19 patients (nine men and 10 women; mean age=43.1 years, SD=11.7) entered the study, the majority of whom were outpatients (73.7%). The patients received riluzole at a mean dose of 168.8 mg/day (SD=27.2) (84.2% took a dose of 150 mg/day or more) for a mean duration of 5.4 weeks (SD=3.7). The mean age at onset of the illness was 23.9 years (SD=12.6), the mean number of lifetime episodes of depression was 8.5 (SD=11.3), and the mean duration of the current episode of depression was 5.4 months (SD=3.7). Most of the patients were of stage 2 or greater treatment resistance (stages 1=47%, 2=31%, 3=11%, 4=0%, and 5=11%). Two subjects had previously failed to respond to lamotrigine therapy.
Sixty-eight percent (N=13) of the subjects completed the 6-week trial. The reasons for discontinuation were adverse events (N=3) (one with increased values on a test of liver function, one with malaise, and one with nausea and vomiting), nonresponse (N=2), and withdrawn consent (N=1). Data were analyzed on an intent-to-treat basis. Dunnett’s multiple range test was used to compare weekly ratings to those at baseline. Significant improvement in score on the Montgomery-Åsberg Depression Rating Scale occurred on weeks 3 through 6 for all patients (F=5.44, df=2, 39, p=0.007) and weeks 2 through 6 for trial completers (F=6.70, df=2, 25, p=0.004) (F1). CGI severity scale and Hamilton anxiety scale scores also improved significantly in weeks 3 through 6 for all patients (F=6.75, df=1.9, 34, p=0.04) and trial completers (F=7.62, df=2.0, 24, p=0.003, and F=5.77, df=1.2, 26, p=0.0007) on the CGI severity scale and Hamilton anxiety scale, respectively. The Hamilton anxiety scale score decreased from a baseline mean of 19.3 (SD=7.7) to a mean of 13.8 (SD=9.4). Response rates (50% decrease in score on the Montgomery-Åsberg Depression Rating Scale) at week 6 for all patients and trial completers were 32% and 46%, respectively. Remission rates (score on the Montgomery-Åsberg Depression Rating Scale <10) at week 6 for all patients and completers were 21% and 31%, respectively. Age, gender, clinical features, and dose of riluzole had no effect on change in scores on the Montgomery-Åsberg Depression Rating Scale. Response rates were higher in subjects receiving a dose of 150 mg/day (response rates at 100 mg/day were one-third [33%]; at 150 mg/day, one-half [50%]; and at 200 mg/day, one-eighth [13%]), although these differences were not statistically different. There were no differences in demographic or clinical variables between responders and nonresponders.
The most common adverse events during the trial were headache (58%), gastrointestinal distress (nausea or vomiting) (43%), decreased salivation (47%), constipation (32%), and tension or inner unrest (26%); similar side effects have been observed with riluzole in trials of patients with amyotrophic lateral sclerosis (8). No serious adverse events were noted. One subject was dropped from the study because of an increase in values in liver function tests to three times the upper normal limit. This subject was asymptomatic for hepatic dysfunction, and liver function values returned to normal shortly after discontinuation of riluzole. There was no relationship between the dose of riluzole and adverse events or changes in laboratory test values.