Shroom & Magic MushroomSuicidal Ideation (SI) Reduction in Treatment-Resistant Depression: Single and Repeated Ketamine Infusion (TRD)

January 5, 2023by Dr.Jake Donaldson0

Suicidal Ideation (SI) Reduction in Treatment-Resistant Depression: Single and Repeated Ketamine Infusion (TRD)

Subanesthetic intravenous ketamine infusions given repeatedly may prolong the fast reduction in suicidal ideation (SI) brought on by a single infusion. The goal of this secondary analysis was to compare the SI decrease caused by a single ketamine infusion to an active control, as well as the sustained suppression of SI caused by ongoing ketamine infusions.

In TRD, ketamine infusions given once weekly were able to keep SI levels from rising after single and repeated infusions. This study contributes to the expanding amount of evidence that ketamine may be a cutting-edge therapy option for SI in mood disorders.


Over two-thirds of suicides, which account for an estimated 1 million deaths annually, take place during a major depressive episode. Although medication is effective in treating major depressive disorder (MDD), up to one-third of patients experience treatment resistance and may continue to be at risk of suicide. Suicidal ideation (SI) is a prevalent symptom of MDD, and the emergence of SI is a significant milestone on the road from suicidal ideas to attempts. SI frequently necessitates swift action, yet relatively few treatments are successful in lowering SI, and none are quick-acting.

Patients with mood disorders have been demonstrated to experience a rapid, albeit brief, reduction in depressed symptoms in response to subanesthetic doses of intravenous (IV) ketamine. Additionally, a recent meta-analysis demonstrated that ketamine can effectively reduce SI when used immediately. Several recent experiments have assessed change in SI with ketamine as a key outcome measure, although preliminary evidence of the effects of ketamine on SI primarily came from secondary analyses of randomized controlled trials examining the antidepressant effects of single ketamine infusions.

  • Fewer studies have looked at the administration of ketamine outside of an acute therapy period, despite the quick relapse rates following a single ketamine infusion. Although a single infusion appears to reduce SI for at least 7 days, findings from open-label trials indicate that anti-suicidal benefits may be sustained with subsequent infusions.
  • There hasn’t been much research looking at the creation of a maintenance plan that would enable the therapeutic benefits of ketamine to be prolonged with less frequent infusions.

In a secondary analysis of data derived from a ketamine augmentation trial involving participants with treatment-resistant depression (TRD) and SI, they tested whether the anti-suicidal effects of ketamine could be augmented through a course of repeated infusions, and whether once-weekly ketamine administration was sufficient to maintain the attenuation of SI obtained with repeated infusions.

  • They have recently shown that this administration strategy extends the duration of depressive symptom remission following repeated infusions.


The results presented here support the quick and cumulative effects of single and recurrent ketamine infusions on suicidal ideation in people with TRD, even for those who had severe SI before treatment. The reduction in SI that was achieved after a single infusion and subsequent infusions was extended with once-weekly treatment in participants who had an antidepressant response to ketamine. Even in participants who did not fulfill the criteria for an antidepressant response, ketamine’s effects on SI appeared to be at least partially independent of those of antidepressants. All participants (92% of the sample) except three experienced a reduction in SI after receiving multiple ketamine infusions, including 14 people who had a notable SI at baseline.

These findings support mounting evidence that ketamine may be an effective treatment for those with acute SI, which is in line with earlier studies.

  • The three patients who didn’t have a SI decline had some of the greatest baseline SI. This result may be in line with recent results that showed people with more severe pre-treatment SI were less likely to experience a SI response to a single ketamine infusion, utilizing pooled data from five clinical trials.

On the other hand, ketamine infusions were beneficial in lowering SI generally even among those with pronounced SI, as revealed by our subgroup analysis.

  • Participants in the current trial experienced a reduction in SI following a single Phase 1 infusion that maintained despite a recurrence of depression symptoms. This reduction continued with subsequent Phase 2 infusions, which were repeated. Although it wasn’t specifically examined, this carry-over effect suggests that ketamine’s antidepressant effects may continue longer than its anti-suicidal effects.

SI considerably lowered after three Phase 2 infusions, according to clinician-administered MADRS-SI scores, however with self-reported QIDS-SI scores, the entire course of six infusions was necessary to produce a meaningful SI decrease. This could be attributed to the fact that the measures and methodologies employed differed. However, subjects had a reduction in SI after each Phase 2 injection, suggesting cumulative effects from both measures. As a result, patients may benefit more from subsequent infusions than they would from a single infusion. With repeated infusions, antidepressant response rates in the current group were doubled.

Present Findings

The current data points to a partial independence between ketamine’s effects on SI and depression. This is corroborated by the finding that changes in depressive symptoms could not account for 60% of the variation in overall SI change. When participants’ depressed symptom scores were taken into account, the participants’ decrease in SI with ketamine remained significant, and several people who didn’t satisfy the antidepressant response criteria with ketamine nonetheless saw a reduction in SI with repeated infusions.

These outcomes are in line with a meta-conclusions analysis’s that ketamine’s effects on SI are not entirely dependent on those on depression symptoms. This partial independence suggests that ketamine may be used to treat SI outside of the context of TRD.


In conclusion, this study demonstrated that both single and recurrent ketamine infusions decreased SI in people with TRD, with cumulative benefits seen with repeated infusions given three times weekly and maintenance of the effects with weekly infusions. These results contribute to the expanding body of data that suggests the promise of ketamine as a novel therapy approach for SI, which currently has few effective treatment choices. Ketamine use may be considered as a potential emergency option for people who are at high risk of suicide as an alternative to more disruptive and expensive hospitalization, according to preliminary evidence of the drug’s quick reduction in SI.


Unknowns are the duration of the anti-suicidal effects of repeated ketamine infusions and whether the ketamine-induced decrease in SI may be sustained with different pharmacological approaches. Further investigation is necessary to ascertain whether decreases in SI following ketamine therapy correspond to a lower risk for suicidal ideation and suicide attempts.




Dr.Jake Donaldson

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