Table 1. Demographic and clinical characteristics of included studies. Table 2. Results of included studies addressing the use of ketamine only. Of the six open-label studies assessing response to single-dose ketamine in MDD, two
were primarily evaluating postulated drug-induced changes to cortical proteins Inhibitors,research,lifescience,medical via 1H-MRS [Salvadore et al. 2012] (n = 14) and serum analysis [Machado-Vieira et al. 2009] (n = 23), and two investigated anterior cingulate cortex activity with regards to drug response [Salvadore et al. 2009, 2010] (n = 11, 15, respectively), but all also reported clinical responses as secondary measures. These four studies showed statistically significant improvement in mood at 230-minute post-infusion time points (p = 0.005 in Salvadore et al. [2009]; p = 0.001 in Salvadore et al. [2010]; p = 0.006 in Salvadore et al. [2012]; p < 0.001 in Machado-Vieira et al. [2009]). A somewhat different model was undertaken in open-label Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical work by Larkin and Beautrais who trialled the feasibility of undertaking single-dose ketamine administration, administered, somewhat atypically for ketamine
studies, as a 0.2mg/kg single bolus over 1–2 minutes, in 14 participants with MDD and suicidal ideation in an emergency department [Larkin and Beautrais, 2011]. A primary aim with this work was to PKI-587 cost evaluate a key conceptual concern about the viability of ketamine use in such ‘real-world’ scenarios. Fitting with previous data they found rapid antidepressive effects within 240 minutes, with 13 (92.3%) meeting
response criteria Inhibitors,research,lifescience,medical and mean scores falling from a baseline MADRS score of 40.4 (standard error of the mean [SEM] = 1.8) to 11.5 (SEM = 2.2). Inhibitors,research,lifescience,medical There are high rates of comorbidity between depressive disorders and substance misuse [Davis et al. 2007]. A family history of alcohol dependency has been shown to result in altered responses to ketamine in healthy participants, and changes to the glutamatergic system and NMDA binding has been implicated in both tuclazepam disorders [Petrakis et al. 2004]. Phelps and colleagues used linear mixed models to evaluate differential response in 26 MDD participants with and without a (self-reported) family history of alcohol dependency to open-label ketamine administration [Phelps et al. 2009]. Those with positive family histories showed a statistically significant improvement over those who did not in MADRS, Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) scores within 230 minutes of ketamine infusion. Individual past alcohol dependency and past family history of depression were not correlated with outcome.