Is Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal Behavior

Chan, Lai Fong; Eu, Choon Leng; Soh, Shean Yih; Maniam, T.; Kadir, Zuri Shahidii; Chong, Benedict Tak Wai; Loo, Jiann Lin; Sharip, Shalisah; Wong, Vincent Choong Wai; Loo, Tsui Huei; Ng, Yin Ping; Kahn, David

doi:10.1097/pra.0000000000000316

Cited by 14 publications

(10 citation statements)

References 40 publications

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“…Our findings reflect those from case report studies of a similar number of individuals with TRD who were tried on maintenance ketamine therapy, 24,25 which also showed that most patients experienced initial but not ongoing improvement.…”

Section: Discussionsupporting

confidence: 86%

Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

et al. 2020

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Background Ketamine has recently received considerable attention regarding its antidepressant and anti-suicidal effects. Trials have generally focused on short-term effects of single intravenous infusions. Research on patient experiences is lacking. Aims To investigate the experiences over time of individuals receiving ketamine treatment in a routine clinic, including impacts on mood and suicidality. Method Twelve fee-paying patients with treatment-resistant depression (6 females, 6 males, age 21–70 years; 11 reporting suicidality and 6 reporting self-harm) who were assessed as eligible for ketamine treatment participated in up to three semi-structured interviews: before treatment started, a few weeks into treatment and ≥2 months later. Data were analysed thematically. Results Most participants hoped that ketamine would provide respite from their depression. Nearly all experienced improvement in mood following initial treatments, ranging from negligible to dramatic, and eight reported a reduction in suicidality. Improvements were transitory for most participants, although two experienced sustained consistent benefit and two had sustained but limited improvement. Some participants described hopelessness when treatment stopped working, paralleled by increased suicidal ideation for three participants. The transient nature and cost of treatment were problematic. Eleven participants experienced side-effects, which were significant for two participants. Suggestions for improving treatment included closer monitoring and adjunctive psychological therapy. Conclusions Ketamine treatment was generally experienced as effective in improving mood and reducing suicidal ideation in the short term, but the lack of longer-term benefit was challenging for participants, as was treatment cost. Informed consent procedures should refer to the possibilities of relapse and associated increased hopelessness and suicidality.

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Section: Discussionsupporting

confidence: 86%

Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

et al. 2020

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“…Another TRBD patient with psychotic depression and suicidality received a single ketamine infusion as an add-on to lamotrigine 200 mg, olanzapine 25 mg and bupropion 300 mg. The patient’s active suicidal ideation resolved 24 h after ketamine infusion [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

“…There is almost no evidence for an augmented antidepressant effect of ketamine–lamotrigine combination in patients with mood disorders so far. It was observed only in case series and a case report [ 53 , 54 ], but considering the burden of bipolar disorder and the lack of rapid-acting strategies for bipolar depression, there is an urgent need for studies investigating this potentially effective strategy. It is necessary to evaluate the safety of this combination.…”

Section: Discussionmentioning

confidence: 99%

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

Wilkowska

Wiglusz

Jakuszkowiak-Wojten

et al. 2022

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Background and Objectives: Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented. Materials and Methods: PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied. Results: Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms. Conclusions: The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine’s side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine–lamotrigine combination in bipolar patients.

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“…Her depressive symptoms partially remitted but she experienced residual cognitive deficits post-ECT which severely impacted her functioning. A previous case series documented her symptomatic remission and significant functional improvement of TRD on intravenous ketamine treatment from 2012-2018 with minimal and transient sideeffects (sedation, nausea and dizziness) that resolved within a week (11). Monthly outpatient maintenance intravenous ketamine was withheld in July 2020 due to concerns about contracting COVID-19 from monthly hospital visits.…”

Section: Case Reportmentioning

confidence: 99%

Case report: Effectiveness of brexpiprazole and esketamine/ketamine combination: A novel therapeutic strategy in five cases of treatment-resistant depression

et al. 2022

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A significant proportion of patients with treatment-resistant depression do not attain functional recovery despite administration of multiple steps of pharmacotherapeutic strategies. This highlights the elusiveness of meeting unmet needs in existing pharmacotherapies for treatment-resistant depression. There is accumulating evidence that antidepressant agents involving the glutamatergic system such as brexpiprazole and esketamine/ketamine have more rapid onset of action and potentially improved effectiveness as an augmentation therapy in treatment-resistant depression. This case series aimed to report five complex cases of unipolar and bipolar treatment-resistant depression where conventional treatment strategies were inadequate in managing high risk suicidal behavior and achieving functional recovery. We discussed further the possible synergistic mechanisms of the novel combination strategy of brexpiprazole and esketamine/ketamine, clinical and patient factors that influenced treatment response, challenges with this combination strategy and implications for future practice and research.

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Is Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal Behavior

Cited by 14 publications

References 40 publications

Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

Case report: Effectiveness of brexpiprazole and esketamine/ketamine combination: A novel therapeutic strategy in five cases of treatment-resistant depression

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