Ketamine's efficacy in depressive disorders has been established in several controlled trials. The aim of a study was to determine whether or not Ketamine administration significantly improves depressive symptomatology in depression and more specifically in major depressive disorder ( MDD ), bipolar depression, resistant depression ( non-ECT studies ), and as an anesthetic agent in electroconvulsive therapy ( ECT ) for resistant depression ( ECT studies ). Secondary outcomes were the duration of ketamine's effect, the efficacy on suicidal ideations, the existence of a dose effect, and the safety / tolerance of the treatment.
Researchers included nine non-ECT studies in the quantitative analysis ( 192 patients with major depressive disorder and 34 patients with bipolar depression ). Overall, depression scores were significantly decreased in the Ketamine groups compared to those in the control groups ( p less than 0.01 ). Ketamine's efficacy was confirmed in major depressive disorder ( resistant to previous pharmacological treatments or not ) ( p less than 0.01 ), in bipolar depression, and in drug-free patients as well as patients under medication.
Four ECT trials ( 118 patients ) were included in the quantitative analysis. One hundred and three patients were diagnosed with major depressive disorder and 15 with bipolar depression. Overall, depression scores were significantly improved in the 58 patients receiving Ketamine in ECT anesthesia induction compared to the 60 patients ( p = 0.04; I2 = 52.4% ).
The duration of ketamine's effects was assessed in only two non-ECT studies and seemed to persist for 2-3 days; this result needs to be confirmed.
Three of four studies found significant decrease of suicidal thoughts and one found no difference between groups, but suicidal ideations were only studied by the suicide item of the depressive scales.
It was not possible to determine a dose effect; 0.5 mg/kg was used in the majority of the studies.
Some cardiovascular events were described ( mostly transient blood pressure elevation that may require treatment ), and Ketamine's use should remain cautious in patients with a cardiovascular history.
The present meta-analysis has confirmed Ketamine's efficacy in depressive disorders in non-ECT studies, as well as in ECT studies.
The results of this first meta-analysis are encouraging, and further studies are warranted to detail efficacy in bipolar disorders and other specific depressed populations.
Middle- and long-term efficacy and safety have yet to be explored.
Extrapolation should be cautious: patients included had no history of psychotic episodes and no history of alcohol or substance use disorders, which is not representative of all the depressed patients that may benefit from this therapy. ( Xagena )
Fond G et al, Psychopharmacology 2014; Epub ahead of print