Characterizing the course of suicidal ideation response to ketamine

Abstract

Background: No pharmacological treatments exist for active suicidal ideation (SI), but the glutamatergic modulator ketamine elicits rapid changes in SI. We developed data-driven subgroups of SI trajectories after ketamine administration, then evaluated clinical, demographic, and neurobiological factors that might predict SI response to ketamine. Methods: Data were pooled from five clinical ketamine trials. Treatment-resistant inpatients (n = 128) with DSM-IV-TR-diagnosed major depressive disorder (MDD) or bipolar depression received one subanesthetic (0.5 mg/kg) ketamine infusion over 40 min. Composite SI variable scores were analyzed using growth mixture modeling to generate SI response classes, and class membership predictors were evaluated using multinomial logistic regressions. Putative predictors included demographic variables and various peripheral plasma markers. Results: The best-fitting growth mixture model comprised three classes: Non-Responders (29%), Responders (44%), and Remitters (27%). For Responders and Remitters, maximal improvements were achieved by Day 1. Improvements in SI occurred independently of improvements in a composite Depressed Mood variable for Responders, and partially independently for Remitters. Indicators of chronic SI and self-injury were associated with belonging to the Non-Responder group. Higher levels of baseline plasma interleukin-5 (IL-5) were linked to Remitters rather than Responders. Limitations: Subjects were not selected for active suicidal thoughts; findings only extend to Day 3; and plasma, rather than CSF, markers were used. Conclusion: The results underscore the heterogeneity of SI response to ketamine and its potential independence from changes in Depressed Mood. Individuals reporting symptoms suggesting a longstanding history of chronic SI were less likely to respond or remit post-ketamine.

Association between plasma levels of BDNF and the antisuicidal effects of repeated ketamine infusions in depression with suicidal ideation

“…10 Ballard et al found that 29% of depressed patients had no or minimal antisuicidal response to a low-dose ketamine (0.5 mg/kg) infusion, which is similar to our findings. 25 Interestingly, this study found no baseline sociodemographic or clinical characteristics that reliably distinguished antisuicidal responders and non-responders. The reasons for no differences in baseline sociodemographic and clinical characteristics between antisuicidal responders and nonresponders were unclear.…”

Ketamine – a prototype of rapidly acting antidepressant drugs

“…Badania ostatnich lat wykazały również redukcję myśli i tendencji samobójczych po podaniu ketaminy, a efekt ten pojawiał się już po kilku godzinach od zakończenia wlewu i utrzymywał się nawet do 10 dni [13][14][15]. Należy jednakże podkreślić, że ketamina była mało skuteczna/nieskuteczna u pacjentów z bardzo nasilonymi i powracającymi myślami samobójczymi [13].…”

“…Badania ostatnich lat wykazały również redukcję myśli i tendencji samobójczych po podaniu ketaminy, a efekt ten pojawiał się już po kilku godzinach od zakończenia wlewu i utrzymywał się nawet do 10 dni [13][14][15]. Należy jednakże podkreślić, że ketamina była mało skuteczna/nieskuteczna u pacjentów z bardzo nasilonymi i powracającymi myślami samobójczymi [13]. Kolejne badania kliniczne wskazują na szybkie przeciwdepresyjne działanie wlewów ketaminy nie tylko w przypadku dużej depresji opornej na klasyczną farmakoterapię [16][17][18] bądź terapię z zastosowaniem wstrząsów elektrycznych [19], ale również w chorobie afektywnej dwubiegunowej [12,17,[20][21][22], zespole obsesyjno-kompulsywnym [23] oraz chronicznej postaci zespołu stresu pourazowego [24].…”

Predicting therapeutic response to oral ketamine for chronic suicidal ideation: a Bayesian network for clinical decision support

“…Ketamine treatment has been shown to result in rapid reductions in both SI and depressive symptoms in several clinical trials [ 11 – 13 ]. However, while ketamine is considered a promising treatment for patients with treatment-resistant depression and SI, individual patients vary in their response to ketamine [ 14 , 15 ], and some individuals do not respond sufficiently, even with serial, titrated treatments. The reasons for the heterogeneity of response to ketamine are unclear but may reflect differences in individuals’ underlying demographic attributes, pathophysiology, genetic makeup, and clinical features [ 10 ].…”

“…In this study the sociodemographic variables of positive family history of alcohol abuse disorder in a first-degree relative, higher BMI and negative history of suicide attempts were associated with improvements in depression scores post- ketamine infusion. Ballard, Yarrington [ 15 ] developed data-driven groups of SI trajectories after ketamine administration, pooled from five clinical ketamine trials. This study evaluated clinical, demographic and neurobiological factors that might predict SI response to ketamine and found that a longstanding history of chronic SI and self- injury were associated with non-response to ketamine.…”