Oral Ketamine in Treatment-Resistant Depression

Abstract

PurposeThe aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.MethodsWe reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.FindingsOver the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.ConclusionsAlthough this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.

Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis

“…Interestingly, in a study of 14 TRD patients given low ketamine doses in the sublingual form (10 mg s.l. ), no efficacy for the treatment of TRBD was seen, and adverse drug reactions were observed [15]. Intra-muscular ketamine doses of 50 mg given every 3, 4 days showed response after 7 days, but on a follow-up in the eight week and later, there was no antidepressant effect in TRBD patients [3].…”

“…To evaluate central nervous system safety, most researchers use the same scales, such as the Clinician Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS) [11,12,14,15]; the Physician Withdrawal Checklist (PWC-20) is also used.…”

“…However, this observation was not replicated when an intranasal esketamine formulation was administered. Another special population needing examination during ketamine administration is represented by TRBD patients, as reported in some studies [3,12,15]. Guidelines of the International College of Neuro-Psychopharmacology (CINP) for Bipolar disorder in adults (CINP-BD-2017) indicate ketamine as an option to treat bipolar depression in TRBD subjects [33].…”

Potential differences in antidepressant effects of oral ketamine liquid suspension versus compounded capsules

“…2,3 Moreover, the effects reported in open-label trials, retrospective chart reviews, case series and case reports similarly show a fairly consistent pattern of limited effects with ketamine capsules with potent effects with the oral liquid suspension. 4,5 Numerous factors may explain the differences in outcomes of capsules versus liquid suspension, including pharmacokinetic differences, which may be particularly important for ketamine, as the rate of infusion plays an important role in both efficacy and adverse effects for intravenous ketamine, suggesting there may be an optimal 'effective infusion rate', which might differ with liquid (increased immediate bioavailability with some sublingual absorption as well) versus capsules. Alternatively, the observation of differential antidepressant effects with liquid suspension versus capsule might be entirely spurious and better explained by the other differences in samples, dosing and study design.…”

Ovarian hormones mediate the prophylactic efficacy of (R,S)-ketamine and (2R,6R)-hydroxynorketamine in female mice

“…However, these medications are slow to provide relief and fail to treat up to 30% of patients (9). These drawbacks have led to the use of (R,S)-ketamine, a commonly-used anesthetic, as a rapid-acting antidepressant for treatment-resistant MDD (TRD) (10,11). When given at sub-anesthetic doses, (R,S)-ketamine has a rapid antidepressant onset of 2 hours in humans and 30 minutes in mice, can last up to 2 weeks, and acts in a sex-specific manner (12)(13)(14)(15).…”