Background:
Ketamine is an emerging treatment for treatment-resistant depression (TRD) associated with rapid and robust improvements in depressive symptoms and suicidality. However, the efficacy and ...safety of ketamine in transitional age youth (TAY; age 18–25) populations remains understudied.
Methods:
In this retrospective analysis, TAY patients (n = 52) receiving ketamine for TRD were matched for sex, primary diagnosis, baseline depression severity, and treatment resistance with a general adult (GA) sample (age 30–60). Patients received four ketamine infusions over 2 weeks (0.5–0.75 mg/kg over 40 min). The primary outcome was the change in Quick Inventory of Depressive Symptomatology Self-Report 16-item (QIDS-SR16) over time. Secondary outcomes were changes in QIDS-SR16 suicidal ideation (SI) item, anxiety (Generalized Anxiety Disorder 7-item (GAD-7)), and adverse effects (ClinicalTrials.gov: NCT04209296).
Results:
A significant main effect of infusions on reduction of total QIDS-SR16 (p < 0.001), QIDS-SR16 SI (p < 0.001), and GAD-7 (p < 0.001) scores was observed in the TAY group with moderate effect sizes, indicative of clinically significant improvements in depression, anxiety, and suicidality. There were no significant differences between TAY and GA groups on these measures over time, suggesting comparable improvements in both groups. Safety and tolerability outcomes were comparable between groups with only mild, transient adverse effects observed.
Conclusion:
Ketamine was associated with comparable clinical benefits, safety, and tolerability in a TAY sample as compared to a matched GA TRD sample.
Background:
The therapeutic potential of subanesthetic doses of ketamine appears promising in unipolar depression; however, its effectiveness in treating bipolar depression (BD) remains uncertain.
...Objective:
This systematic review aimed to summarize findings on the use of ketamine for the treatment of BD by assessing its efficacy, safety, and tolerability.
Design:
Systematic review.
Methods:
We conducted a systematic review of studies that investigated the use of ketamine for adults with BD. We searched PubMed and Embase for relevant randomized-controlled trials, open-label trials, and retrospective chart analyses published from inception to 13 March 2023.
Results:
Eight studies were identified pooled n = 235; mean (SD) age: 45.55 (5.54). All participants who received intravenous (IV) ketamine were administered a dose of 0.5–0.75 mg/kg as an adjunctive treatment to a mood-stabilizing agent, whereas participants who received esketamine were administered a dosage ranging from 28 to 84 mg. Flexible dosing was used in real-world analyses. A total of 48% of participants receiving ketamine achieved a response (defined as ⩾50% reduction in baseline depression severity), whereas only 5% achieved a response with a placebo. Real-world studies demonstrated lower rates of response (30%) compared to the average across clinical trials (63%). Reductions in suicidal ideation were noted in some studies, although not all findings were statistically significant. Ketamine and esketamine were well tolerated in most participants; however, six participants (2% of the overall sample pool, 5 receiving ketamine) developed hypomanic/manic symptoms after infusions. Significant dissociative symptoms were observed at the 40-min mark in some trials.
Conclusion:
Preliminary evidence suggests IV ketamine as being safe and effective for the treatment of BD. Future studies should focus on investigating the effects of repeated acute and maintenance infusions using a randomized study design.
Clinical trials have demonstrated therapeutic potential of intravenous (IV) ketamine in unipolar depression; however, its effectiveness and safety in treating bipolar depression (BD) remains ...uncertain. This thesis aimed to assess the efficacy, effectiveness, safety and tolerability of IV ketamine for BD. A systematic review was conducted to synthesize the currently available evidence on ketamine for BD. Additionally, a retrospective analysis was conducted, evaluating outcome data of outpatients with BD that received an acute course of four ketamine infusions. The systematic review found that 48% of participants receiving ketamine achieved response, whereas only 5% achieved response with placebo. Real-world data showed statistically and clinically significant antidepressant effects of ketamine in the overall sample (n=66). Preliminary evidence suggests IV ketamine has a favourable safety and efficacy profile for the treatment of BD. Future studies should focus on investigating the effects of repeated acute and maintenance infusions using a randomized study design.
Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD).
A systematic review of ...clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo.
Five randomized-controlled trials reported on the efficacy of KAP treatment and discussed active mechanisms. Four of the studies treated adults with SUD and a single study treated adults with TRD. Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD found no benefit.
Lack of large, replicated clinical trials. No studies actively examining mechanisms of action.
Evidence suggests that temporary neural changes caused by ketamine such as n-methyl-d-aspartate receptor (NMDAR) inhibition and increase of synaptic neuroplasticity affect treatment outcomes of KAP. Based on reports of preliminary findings, we speculate that adjunct psychotherapy, changes in perspective, and spirituality may also play a role.
•Limited number of clinical trials examine ketamine-assisted psychotherapy.•Psychotherapy, shift in mindset, and spirituality may influence treatment outcome.•Future studies should investigate mechanisms in ketamine-assisted psychotherapy.
Objectives: Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the accessibility and ...scalability of oral ketamine make it preferred over intravenous ketamine. In this systematic review, we aim to evaluate the efficacy, tolerability, and safety of oral ketamine, esketamine and r-ketamine for unipolar and bipolar depression. Materials and methods: Electronic databases were searched from inception to September 2022 to identify relevant articles. Results: Twenty-two studies, including four randomized clinical trials (RCTs), one case series, six case reports, five open-label trials and six retrospective chart review studies involving 2336 patients with depression were included. All included studies reported significant improvement following ketamine administration. Ketamine was well tolerated without serious adverse events. However, RCTs had a high risk of bias due to analysis methods and adverse events monitoring. Ketamine dosage varied from 0.5 to 1.25 mg/kg. The frequency of administration was daily to monthly. Several important limitations were identified, most notably the small number of RCTs. Conclusions: Taken together, preliminary evidence suggests the potential for antidepressant effect of oral ketamine. However, further research with large sample size and long follow-up period is needed to better determine the antisuicidal effect and efficacy in treatment-resistant depression.
Background
Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar ...depression. Herein, we describe the real‐world effectiveness of repeated ketamine infusions for treatment‐resistant bipolar depression.
Methods
This study was conducted in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). In this observational study (NCT04209296), patients with treatment‐resistant bipolar I/II depression (n = 66) received four sub‐anesthetic doses of IV ketamine (0.5–0.75 mg/kg) over a two‐week period. Symptoms of depression, suicidality, anxiety, and functioning were assessed with validated self‐report measures.
Results
Statistically and clinically significant antidepressant effects were observed in the overall sample, as measured by the Quick Inventory for Depression Symptomatology‐Self Report‐16 (QIDS‐SR16) with further reductions in depressive symptoms observed after each subsequent infusion (n = 66; mean QIDS‐SR16 reduction of 6.08+/−1.39; p < 0.0001). Significant reductions of suicidal thoughts (QIDS‐SR16‐Suicide Item) and anxiety (Generalized Anxiety Disorder‐7) were also observed with functional improvements on the Sheehan Disability Scale (p < 0.0001 on all measures). Moreover, the response rate (QIDS‐SR16 total score decrease ≥50% from baseline) was 35% and remission rate (QIDS‐SR16 total score ≤5) was 20% after four infusions. Infusions were generally well tolerated with treatment‐emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis.
Conclusions
Real‐world effectiveness of IV ketamine for bipolar depression was observed. Repeated doses were associated with greater symptom reduction and adequate tolerability.
•Comorbidity of borderline personality disorder (BPD) with depression is common.•Comorbid BPD is often associated with poorer response to antidepressants.•Ketamine was as effective for the ...BPD-positive sample as it was for participants without BPD.•BPD was not associated with poorer response to ketamine.•Ketamine was associated with improvements in core symptoms of BPD.
Borderline personality disorder (BPD) has high rates of comorbidity with mood disorders, including treatment-resistant depression (TRD). Comorbidity of BPD with depression is associated with poorer response to antidepressants. Intravenous ketamine is a novel treatment for TRD that has not been specifically evaluated in patients with comorbid BPD. In this retrospective analysis of data collected from participants who received care at the Canadian Rapid Treatment Centre of Excellence (CRTCE; Braxia Health; ClinicalTrials.gov: NCT04209296), we evaluated the effectiveness of intravenous ketamine in a TRD population with comorbid BPD (N=100; n=50 BPD-positive compared with n=50 BPD-negative). Participants were administered four doses of intravenous ketamine (0.5-0.75mg/kg over 40 minutes) over two weeks. The primary outcome measures were changes in depressive symptom severity (as measured by Quick Inventory of Depressive Symptomatology–Self Report 16-item (QIDS-SR16)) and borderline symptom severity (as measured by Borderline Symptom List 23-item (BSL-23)). Both BPD-positive and BPD-negative groups improved significantly on the QIDS-SR16, QIDS-SR16 suicide ideation item, anxiety, and functionality scales with large effect sizes. There was no significant difference between groups. The BPD-positive group exhibited significant reduction of 0.64 on BSL-23 scores and a significant reduction of 5.95 on QIDS-SR16 scores. Patients with TRD and comorbid BPD receiving ketamine exhibited a significant reduction in symptoms of depression, borderline personality, suicidality, and anxiety.
