Real-world depression, anxiety and safety outcomes of intramuscular ketamine treatment: a retrospective descriptive cohort study

Abstract

Background Ketamine has emerged as a promising pharmacotherapy for depression and other mental illnesses, and the intramuscular (IM) administration of ketamine is now offered at many North American outpatient psychiatric clinics. However, a characterization of the outpatient population receiving IM ketamine treatment and an evaluation of the real-world depression, anxiety, and safety outcomes of long-term psychiatric IM ketamine treatment has not been reported. This study aimed to evaluate the clinical characteristics, treatment patterns, clinical outcomes, and adverse events of patients receiving IM ketamine treatment. Methods Patient data from the electronic health records of a private outpatient psychiatric clinic network in the United States were collected and analyzed retrospectively. Adults with any psychiatric diagnosis who received ketamine treatment only by IM administration from January 2018 to June 2021 were included. A total of 452 patients were included in the cohort. Results Patients receiving IM ketamine treatment had a mean of 2.8 (SD 1.4) psychiatric diagnoses. 420 (93%) patients had a diagnosis of major depressive disorder, 243 (54%) patients had a diagnosis of generalized anxiety disorder, and 126 (28%) patients had a diagnosis of post-traumatic stress disorder. Patients received a median of 4 (range 1–48) IM ketamine treatments. Median depression scores (PHQ-9) improved 38% from 16.0 (IQR 11.3–21.8) at baseline to 10.0 (IQR 6.0–15.0) at last treatment (p < .001). Median anxiety scores (GAD-7) improved 50% from 14.0 (IQR 8.0–17.0) at baseline to 7.0 (IQR 4.3–11.8) at last treatment (p < .001). With maintenance ketamine treatments, average improvements in depression (PHQ-9) and anxiety (GAD-7) scores of at least 4.7 and 4.9 points were maintained for over 7 months. An adverse event occurred during 59 of 2532 treatments (2.3%). Conclusions IM ketamine is being utilized to treat psychiatric outpatients with multiple mental illnesses not limited to depression. Average depression and anxiety levels significantly improve throughout IM ketamine treatment and do not regress to baseline during patients’ maintenance treatment phase. Prospective studies are recommended to confirm the long-term effectiveness and safety of IM ketamine.

Intravenous ketamine for benzodiazepine deprescription and withdrawal management in treatment-resistant depression: a preliminary report

“…In our real-world sample of severe unipolar and bipolar TRD patients, nearly 50% received long-term BZDR, with an elevated average daily dose of 15.6 mg (diazepam equivalent). Indeed, similarly elevated rates of benzodiazepine prescription have been found in other studies of ketamine [ 4 , 58 ], congruent with the two to threefold increased risk of sedative use disorder in TRD [ 59 ]. Preliminary evidence further suggests a potential correlation between BZDRs and more severe/chronic illness courses in depression (although the causality of this link has yet to be established) [ 60 ].…”

“…Approximately 30-50% of patients with depression are prescribed benzodiazepines and/or z-drugs (also known as Benzodiazepines and Related Drugs (BZDRs)) at some point during their illness [1]. Although international depression guidelines generally recommend only short-term BZDR use [2], chronic use eventually arises in 10-15% of patients with depressionparticularly those with treatment resistant depression (TRD) [3,4]. Long-term BZDR use has been linked to increased risks of falls and motor-vehicle accidents, cognitive impairment, suicide, and drug overdose mortality [5][6][7][8][9].…”

Multidisciplinary development of guidelines for ketamine treatment for treatment-resistant major depression disorder for use by adult specialist mental health services in New Zealand

“…We chose the dose of 1 mg/kg because of recent clinical trial and ‘real-world’ evidence that 0.5 mg/kg is an ineffective dose for some, and to optimise the likelihood of response. 20 , 21 Alternative routes include intravenous and subcutaneous administration. These have been shown to produce similar antidepressant effects in a small ascending dose study, although plasma ketamine levels are higher when given intravenously.…”

Pharmacotherapy and Ketamine Assisted Psychotherapy for Treatment-Resistant Depression

“…12,13 Observational studies have reported that ketamine administrated via intramuscular and oral routes is also effective for patients with depression and anxiety. [14][15][16] More recently, esketamine nasal spray, the S(+) enantiomer of ketamine, was approved by the FDA in 2019 for treatment of TRD in conjunction with an oral antidepressant. 17 The bioavailability of intravenous, intramuscular, intranasal, oral, and rectal ketamine is 100%, 93%, 8%-45%, 17%-29%, and 11%-25%, respectively.…”