RESUMO
Background: Intravenous (IV) ketamine is a rapid acting antidepressant used primarily for treatment-resistant depression (TRD). It has been suggested that IV ketamine's rapid antidepressant effects may be partially mediated via improved sleep and changes to the circadian rhythm. Objectives: This study explores IV ketamine's association with changes in patient-reported sleep quality and circadian rhythm in an adult population with TRD. Methods: Adult patients (18-64 years) with TRD scheduled for IV ketamine treatment were recruited to complete patient rated outcomes measures on sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and circadian rhythm using the Morningness-Eveningness Questionnaire (MEQ). Over a 4-week course of eight ketamine infusions, reports were obtained at baseline (T0), prior to second treatment (T1), prior to fifth treatment (T2), and 1 week after eighth treatment (T3). Results: Forty participants with TRD (mean age = 42.8, 45% male) were enrolled. Twenty-nine (72.5%) had complete follow-up data. Paired t tests revealed statistically significant improvements at the end of treatment in sleep quality (PSQI) (p = 0.003) and depressive symptoms (Clinically Useful Depression Outcome Scale-Depression, p < 0.001) while circadian rhythm (MEQ) shifted earlier (p = 0.007). The PSQI subscale components of sleep duration (p = 0.008) and daytime dysfunction (p = 0.001) also improved. In an exploratory post hoc analysis, ketamine's impact on sleep quality was more prominent in patients with mixed features, while its chronobiotic effect was prominent in those without mixed features. Conclusion: IV ketamine may improve sleep quality and advance circadian rhythm in individuals with TRD. Effects may differ in individuals with mixed features of depression as compared to those without. Since this was a small uncontrolled study, future research is warranted.
Patient-reported changes in sleep during treatment with intravenous ketamine for depression Intravenous ketamine is a fast acting treatment for depression that does not respond to more conventional antidepressant medications. Almost all people with depression have problems with sleep as a symptom of their illness. This can include things like difficulties falling asleep, problems staying asleep, sleeping more or less than usual, and shifting the sleep schedule to stay up later than usual. It has been previously suggested that improving sleep in people with depression may be part of how ketamine exerts its antidepressant effect. This study surveyed patients with depression who received eight intravenous infusions of ketamine (two per week for 4 weeks) to ask them about their sleep quality and patterns before treatment, part way through their course of treatment and after the treatments were completed. Symptoms of depression were also measured. Data were collected on 29 people. People reported overall that sleep quality did improve with ketamine treatments, and that timing of sleep shifted earlier. Sleep duration increased and people had less problems with daytime functioning. There is a subtype of depression called depression with "mixed features," meaning that these people, in addition to being depressed, may have some activating symptoms like irritability, restlessness, and agitation. It is thought that this type of depression may be biologically different from depression without these symptoms. In this study, around half (15/29) had mixed features. Sleep quality improved only in the group without mixed features. On the other hand, the group with mixed features had their sleep schedule shift earlier, but the group without mixed features did not. This supports the idea that these two types of depression may be biologically different, and ketamine treatment may exert different effects on the sleep of each group. This was a small study, but suggests a need for future research.
RESUMO
Ketamine has gained rapid popularity as a treatment option for treatment resistant depression (TRD). Though seen only in limited contexts, ketamine is a potential drug of abuse, addiction and diversion. Clinical ketamine studies to date have not systematically evaluated factors relevant to addiction risk in patients with TRD, but in treating patients with ketamine, risks of potential harms related to addiction must be considered. As clinical access to intravenous ketamine programs is limited in much of Canada, these considerations become even more important for clinicians who elect to offer patients less supervised, non-parenteral forms of ketamine treatment. This study explores factors relevant to addiction risk in a real-world sample of 33 patients with TRD currently or previously treated with sublingual (SL) or intranasal (IN) ketamine in the community. First, patients were surveyed using a Drug Liking and Craving Questionnaire (DLCQ) to assess their level of drug liking and craving for ketamine, and to screen for symptoms of a ketamine use disorder. Second, the pharmacy records of these patients were reviewed for red flags for addiction such as dose escalation or early refills. Third, surveys were administered to the treating psychiatrists of patients who had discontinued ketamine to determine if abuse concerns contributed to reason for discontinuation. Though limited to a small sample, results indicate that ketamine is not a universally liked or craved substance in patients with TRD. Prescribers of non-parenteral ketamine should monitor patients and prescribe cautiously. Factors related to addiction (as in the DLCQ) should be explored for clinicians to consider individual risk/benefit for judicious use of ketamine in patients with TRD.