Low‐dose ketamine infusion in treatment‐resistant double depression: Revisiting the adjunctive ketamine study of Taiwanese patients with treatment‐resistant depression

Abstract

Background: Whether a single low-dose ketamine infusion may have rapid antidepressant and antisuicidal effects in patients with treatment-resistant double depression remains unclear.Methods: This study enrolled 35 patients with treatment-resistant double depression, 12 of whom received 0.5 mg/kg ketamine, 11 received 0.2 mg/kg ketamine, and 12 received normal saline as a placebo. The patients were assessed using the 17item Hamilton Rating Scale for Depression (HDRS) prior to the initiation of infusions, at 40 and 240 min post-infusion, and sequentially on Days 2-7 and on Day 14 after ketamine or placebo infusions.Results: A single 0.5 mg/kg ketamine infusion had rapid antidepressant (p = 0.031, measured by the HDRS) and antisuicidal (p = 0.033, measured by the HDRS item 3 scores) effects in patients with treatment-resistant double depression. However, 0.2 mg/kg ketamine was insufficient to exert rapid antidepressant and antisuicidal effects in this patient population with severe and chronic illness.Discussion: In this patient population, the commonly used dose of 0.5 mg/kg was sufficient. Additional studies are required to investigate whether repeated infusions of low-dose ketamine may also maintain antidepressant and antisuicidal effects in patients with treatment-resistant double depression.

The Pharmacology and Clinical Applications of Psychedelic Medicines Within Midwifery Practice

“…Researchers found that the higher dosing (0.5 mg/kg) led to a significant reduction in depression and suicidal symptoms but not in anxiety distress symptoms. The lower dose (0.2 mg/kg) did not show a rapid reduction in depression symptoms and suicidal ideation 40 . A systematic review of 6 randomized, placebo‐controlled double‐blind clinical trials completed between 1990 and 2013 with participants diagnosed with unipolar and bipolar MDD diagnoses showed that ketamine can rapidly improve depressive symptoms both one day and 7 days after infusion 41 .…”

“…The lower dose (0.2 mg/kg) did not show a rapid reduction in depression symptoms and suicidal ideation. 40 A systematic review of 6 randomized, placebo-controlled double-blind clinical trials completed between 1990 and 2013 with participants diagnosed with unipolar and bipolar MDD diagnoses showed that ketamine can rapidly improve depressive symptoms both one day and 7 days after infusion. 41 Another systematic review of 28 primary studies demonstrated that a single infusion of ketamine reduced clinical depression symptoms within 24 hours and that the benefits were sustained for between 6.8 and 30 days for the 4 single-infusion studies that measured relapse times.…”

The conundrum of therapeutic intoxication

“…In the only positive trial of esketamine, people allocated to placebo improved by a huge 17.0 points on the Montgomery-Åsberg Depression Rating Scale over 4 weeks. 3 Having said this, we accept that people may occasionally gain insights through the use of psychoactive substances, though this is not necessarily restricted to psychedelics, and there are safer routes to personal development such as exercise, art, exposure to nature and psychotherapy.…”

“…Subjective ‘happiness’ during ketamine infusions, for example, appears to predict antidepressant response over time. 3 Crucially, this acute effect predicts responses at follow-up assessment points beyond the mere ‘hours’ mentioned by Horowitz and Moncrieff, and rather extends to 2 weeks post-administration. These and other data suggest that positively experienced drug intoxication in carefully screened, well-controlled and psychologically informed treatment contexts can occur safely 4 and mediate subsequent benefits that persist well beyond the day of administration.…”

“…This editorial on the use of intramuscular clozapine 1 has the potential to mislead readers. The authors question the efficacy of intramuscular clozapine on the grounds that it is not always given when prescribed 2,3 and go on to recommend the use of intramuscular haloperidol or olanzapine as alternatives to intramuscular clozapine. Most patients who respond to clozapine are willing to continue taking it once their insight has improved but may be initially reluctant while acutely unwell.…”