Insomnia and anxiety exhibit distinct short-term associations following ketamine in treatment-resistant depression

Abstract Insomnia and anxiety frequently co-occur with treatment-resistant depression (TRD). This study examined short-term changes in depression, anxiety, and insomnia symptoms post-ketamine in TRD and their inter-relationships. Seventy-one patients with TRD were assessed at baseline and 24 h after intravenous ketamine (0.5 mg/kg). Depression, anxiety, and insomnia were measured using the Montgomery–Åsberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), and insomnia items from the Hamilton Depression Rating Scale (HAM-D), respectively. Linear mixed-effects models tested pre–post changes, while Spearman, Pearson, and simple linear regression examined associations between symptom domains. As an exploratory analysis, linear discriminant analysis (LDA) and logistic regression were used to classify insomnia improvement. All symptom domains decreased significantly post-ketamine treatment, including depression (MADRS; β = –11.72, P < 0.001), anxiety (HAM-A; β = –7.87, P < 0.001), and insomnia ( β = –0.89, P < 0.001). At baseline, insomnia was moderately correlated with anxiety (Spearman ρ = 0.36), and anxiety was correlated with depression (Pearson r = 0.39); similar associations were observed post-ketamine (Spearman ρ = 0.36; Pearson r = 0.57). Changes in anxiety were strongly associated with changes in depression (Spearman ρ = 0.61), whereas changes in insomnia were not significantly associated with changes in either domain. Greater baseline insomnia severity was associated with larger absolute insomnia reductions. Exploratory polysomnography analyses suggested short-term increases in total sleep time, slow-wave sleep, and sleep efficiency, and reduced sleep latency. In conclusion, although all symptom domains decreased post-ketamine, short-term changes in HAM-D insomnia symptoms were not significantly associated with changes in depression or anxiety in TRD. Clinical Trial Identifier : www.clinicaltrials.gov (NCT00088699)