Is there a future for other glutamate receptor modulators in the pharmacotherapy of mood disorders?

Abstract

There is increasing evidence that some glutamatergic drugs could have antidepressant effects. Ketamine as a promising prototype for novel glutamatergic antidepressants has a much faster onset of action and is possibly more efficacious than standard antidepressants.1 Two recent systematic reviews and meta-analyses assessed the antidepressant efficacy (including modes of administration, duration of effect and adverse effects) of ketamine and other glutamate receptor modulators in the treatment of unipolar depression (Caddy et al ,2 in the Cochrane Database of Systematic Reviews), and, more generally, in mood disorders (Newport et al ,3 in the American Journal of Psychiatry). In their review, Caddy et al conducted searches of the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register , which includes relevant randomised controlled trials (RCTs) mainly from the Cochrane Library, MEDLINE, EMBASE and PsycINFO. Additionally, they searched the WHO's trials portal (ICTRP) and ClinicalTrials.gov to identify unpublished or ongoing studies up to January 2015, and contacted authors to request additional trial data. The primary outcomes for this study were response rate and adverse events. Secondary outcomes included remission rate, mean end point scores or mean change scores, suicidality and drop-out rates. They included trials recruiting participants with treatment-resistant unipolar depression (except for one in the trial of Berman et al ) with all interventions as either monotherapy or combined with other treatments. Of note, the review of Caddy et al belongs to one of a pair of Cochrane reviews, which focuses on glutamate receptor modulators in bipolar disorder (BD).3 The authors rigorously assessed each trial for all potential sources of bias, namely, selection bias, performance bias, detection bias, attribution bias, reporting bias and other bias. They considered only data from the first phase of cross-over trials, calculated response rates out of the total number of randomised participants and applied …