Table 1.
Clinical Trials in Psychiatry
| Author | Subjects | Study design | Adverse Effects | Key Findings |
|---|---|---|---|---|
| Zarate et al. (2004) | 19 adults with depression 13 completed trial |
Open-label; One-week drug-free period followed by riluzole alone, 100–200 mg/day (avg 169 mg) for 6 weeks | One subject who had three times elevation of liver function tests which normalized after discontinuation of drug. | 46% of study completers had ≥50% decrease in MADRS scores at week 6. Improvements observed on HAM-D and HAM-A. |
| Coric et al. (2005) | 13 adults with OCD | Open-label; 50 mg of riluzole added to current treatment | No major adverse effects. | 7 had >35% reduction in CY-BOCS scores; 5 had >35% reduction in CY-BOCS and a final Y-BOCS of 16 or less. |
| Initially treated for 6 weeks then extended to 12 weeks. | One patient's initially elevated alanine aminotransferases (ALT) declined with study progression. | HAM-D and HAM-A scores also improved significantly over time, with mean scores dropping from 30 (± 13.7) at baseline to 19.7 (± 6.0) and from 18.2 (± 6.2) to 12 (± 2.5), respectively. | ||
| Mathew et al. (2005) | 18 adults with GAD 15 completed trial |
Open-label; 100 mg riluzole/day for 8 weeks after 2-week drug washout. | No major adverse effects | Median response time was 2.5 weeks. 12 subjects had ≥50% decrease on HAM-A scores at study completion. Mean scores dropped from 20 (± 3.4) at baseline to 7.5 (± 5.3) at week 8. 8 patients were in remission at study completion (HAM-A score of ≤7). |
| Zarate et al. (2005) | 14 adults with depression and bipolar disorder. 8 completed trial |
Open-label; Supplementation of 50–200 mg daily riluzole if still depressed (MADRS score ≥20) after 4-week treatment with lithium. | 2 subjects had elevations in liver function tests which normalized after discontinuation of the drug. | Significant improvements on the MADRS, with 7 subjects entering remission (MADRS score of ≤12) at the end of 8-week trial. |
| Riluzole supplemented 8 weeks thereafter. | No switch to mania or hypomania. | |||
| Grant et al. (2007) | 6 children with OCD (ages 8–17, mean 14.4 years) | Open-label; 100–200 mg riluzole daily added to previously prescribed medications for 12 weeks (2 subjects not on any other medication at baseline). | No major adverse effects | 4 out of 6 subjects were Much- or Very Much-Improved on the CGI scale. 39% reduction on CY-BOCS for the group as a whole. 1 subject improved later |
| Sanacora et al. (2007) | 15 adults with MDD 10 completed trial |
Open-label; 50 mg riluzole added for 6 weeks to ongoing medication regimen, followed by optional 6-week continuation phase. | No major adverse effects | HAM-D and HAM-A scores decreased by 36% and 31%, respectively, from baseline by the end of week 6. |
| Response time was as early as 1 week and remained significant for entire study phase. | ||||
| Pittenger et al. (2008) | 13 adults with OCD (9 also had concomitant MDD. | Open-label; 50 mg twice a day (bid) up to 100 mg bid; other medicines adjusted ad lib. | No major adverse effects | 6 of 13 subjects had ≥35% reduction in Y-BOCS in 12 weeks. 2 others improved later. ≥31% drop in average scores on HAM-A, ≥28% drop in average scores on HAM-D. |
| Mathew et al. (2009) | 26 medication-free adults with MDD. | Double-blind; Ketamine (IV) administered 0.5 mg/kg over 40 min after pre-treatment two hours prior with 300 mg lamotrigine or placebo. Among those whose depression failed to improve at 72 hours participated in a 32-day double-blind trial of riluzole 100–200 mg/day. |
No major adverse effects | 65% responded to treatment, with ≥50% reduction on MADRS 24 hours after ketamine. Lamotrigine did not attenuate the side effects nor enhance antidepressive effects. No significant difference in time-to-relapse between riluzole and placebo. Thus, early termination of study. |
Abbreviations: bid = twice a day; CGI = Clinical Global Impressions; CY-BOCS = Children's Yale-Brown Obsessive-Compulsive Scale; GAD = generalized anxiety disorder; HAM-A = Hamilton Anxiety Scale; HAM-D = Hamilton Depression Scale; MDD = major depressive disorder; MADRS = Montgomery-Åsberg Depression Rating Scale; OCD = obsessive-compulsive disorder; Y-BOCS = Yale-Brown Obsessive-Compulsive Scale.