Parenteral Route Research Articles

Hemodynamic assessment of transitioning from parenteral prostacyclin to selexipag in pediatric pulmonary hypertension.

Despite the increase in therapeutic options, parenteral prostacyclins remain the cornerstone in the medical management of pulmonary arterial hypertension (PAH). While the use of parenteral prostacyclins in pediatric patients is well documented, less is known about alternative drug delivery methods such as enteral administration. Given that parenteral routes of prostacyclin administration (IV or SC) are invariably accompanied by complicated logistics and lifestyle compromises, enteral prostacyclin administration represents an attractive treatment option. Selexipag (Uptravi®) was approved for adults PAH in 2015. There is limited data on the hemodynamic efficacy of transitioning from parenteral prostacyclins to selexipag, particularly in the pediatric population. We report 11 pediatric PAH patients who underwent this transition, in which 10 had complete cardiac catheterization data before and following the transition to selexipag. All patients/families reported an improvement in quality of life, and the transitions occurred without adverse effects. However, 3 of the 11 (27%) did not tolerate the transition; two for worsening hemodynamics, and one for acute right ventricular failure in the setting of an intercurrent illness. In addition, the transition to selexipag was associated with a modest increase in pulmonary vascular resistance index (6/10) and decrease in cardiac index (6/10) in some patients. Selexipag use in pediatric PAH represents a significant addition to our therapeutic arsenal, and its use provides a meaningful improvement in quality of life compared with other prostacyclin formulations. However, when goals of care include aggressive disease management, a decision between improved quality of life and possible adverse outcomes must be considered, and its substitution should include cautious, close, long-term follow-up.

A Promising Oral Drug Delivery System of Microsponges: A Brief Review

In the modern era of drug delivery, microsponges have their own tremendous properties of porous nature, due to this porous nature they have a capacity to entrap active drug and acts as a drug carrier because of this entrapment controlling the drug release and targeting the drug to a particular site is possible. Initially, this microsponge drug delivery has been used for topical route and later on oral route, recently, researches focused on the pulmonary and parenteral route of delivery. The present review aims at the development of microsponge technology in oral drug delivery, preparation, formulation considerations, characterization, recent advancements, and future prospects of microsponge drug delivery.

Self-regulated Anti-Overdose Crush and Extraction-Resistant Drug Delivery System to Combat Opioid Overdose Crisis.

Pharmaceutical opioid dosage forms are commonly misused via an oral route in non-manipulated form, i.e., overdose in intact form, or manipulated form, i.e., after crushing the dosage form, and also via the non-oral route in manipulated form, particularly the parenteral or nasal route. To assess the self-regulated anti-overdose property, crushing strength, extractability, and syringeability of the developed drug delivery system by in vitro laboratory studies. Tapentadol HCl drug particulates fabricated using different polymers were assessed for extractability studies in 25 ml of water at room temperature (RT) and at > 90°C. Crushing strength was assessed by grinding the drug particulates in a mortar and pestle and a coffee grinder for 1 min. For syringeability, an attempt was made to withdraw the drug mixture using a 1 ml insulin syringe for 1 min. To assess the self-regulated anti-overdose property, in vitro dissolution testing on a single-capsule per dissolution vessel (normal condition) and four-capsules per dissolution vessel (overdose condition) was performed. POLYOX, Natrosol, and Blanose-containing drug particles retarded drug extraction by > 80% at RT and > 90°C. After 1 min of grinding in a mortar and pestle and a coffee grinder, crushed POLYOX-containing drug particulates were retained at > 99% on the ASTM-170# screen. The attempt to withdraw the viscous mixture of drug formulation prepared with 5 ml of water for 1 min using a 1 ml insulin syringe was unsuccessful. In dissolution studies, more than 90% of the drug was released in normal conditions, and more than 90% of the drug was retarded in overdose conditions. In vitro laboratory studies demonstrate that the developed self-regulated anti-overdose crush-resistant drug delivery system may deter misuse via oral and non-oral routes.

From the Limit Test for Trace Elements Control to the Elemental Impurities Analysis by Inductively Coupled Plasma Optical Emission Spectrometry: Application on Six Samples of Metronidazole API

IntroductionThe objective of this work was to control the inorganic impurities by the trace elements and sulfuric ashs limit tests and to analyze the elemental impurties by Inductively Coupled Plasma Optical Emission Spectrometry (ICP OES) wich is a novel method based on security data in six samples of Metronidazole API, collected from six pharmaceutical industries installed in Algeria. Materials and MethodsFor the trace elements and sulfuric ashs limit tests, a muffle furnace and a sand bath were used for samples calcination and each sample was processed according to the limit tests of European Pharmacopoeia eighth edition (Eur Ph 8 th ed). For the elemental impurities analysis, an ICP OES device was used for analysis of trace elements in diverse samples and each sample was processed according to the new procedures of American Pharmacopoeia USP 40-NF 35. ResultsThe results of trace elements and sulfuric ashs limit tests showed that all samples were conform except M1 sample wich contained more than 20 ppm of trace elements. The ICP OES elemental impurities analysis showed that the content of class 1 elements (Cd, Pb, As and Hg) and class 3 elements (Cu, Sn and Cr) of all samples was in the required limits. The content of class 2 elements (Co, Ni and Ag) was in the required limits in all samples except M3 sample which had Nickel content (3.5 ppm) exceeded the authorized limit for the parenteral route (2 ppm). Knowing that Nickel interferes very weakly with Osmium, this may be explained by the fact that this sample was intended to be put into oral forms. ConclusionThe highlighting of Nickel impurity exceeding safety standards confirm that trace elements test is neither specific nor exact, so it's recommended to manufacturers and quality control laboratories to apply the new procedures based on safety data which are well described in the new chapters (232) and (233) of USP or the general chapter 2.4.20 of Eur Ph.

Exposure of aluminium to C6 glioma cells modulates molecular and functional neurotoxic markers.

The risk of aluminium exposure to humans is very high as it may get into the human body through excessive dietary contaminants, inhalation of fine particulate matter, or through parenteral routes as a vaccine adjuvant and so forth. The increased level of aluminium in brain tissue has been shown to be associated with several neurodegenerative and neurotoxic adverse effects, including AD. However, the exact mechanism of aluminium-induced neurotoxicity is still unclear. Therefore, our study aimed to investigate the mechanism of neurotoxic and neurodegenerative effects through in vitro exposure of aluminium in rat glioma C6 cell line. The findings of our study have indicated that aluminium chloride exposure may lead to alteration in acetylcholine levels, increased oxidative imbalanceand induction of molecular structural and functional markers of neuronal inflammation. This study also demonstrated that aluminium exposure may lead to the induction of caspase-3 along with apoptotic cell death and a significant increase in amyloid-beta and hyperphosphorylated tau levels in C6 cells. Thus, this study may provide a mechanistic understanding of the regulation of neuroinflammatory and neurodegenerative biomarkers due to aluminium exposure.

Immunogenicity of inactivated Escherichia coli O157:H7 with Stx2B microparticle in mice.

Objective(s):Vaccination using inactivated bacteria is one of the most effective ways to protect against EHEC infection. Escherichia coli O157:H7 infections are mainly influenced by Shiga toxins (Stx) and attaching/effacing factors. Among various factors, Stx2B is gaining much attention as a vaccine candidate. Formulating an inactivated bacteria with a suitable adjuvant increases vaccine efficacy and antibody production and can lead to a lasting immune response and protection against O157:H7. Materials and Methods:To assess vaccine efficacy, in this study, we have considered heat and formalin-inactivated bacteria along with chitosan-coated Stx2B/ Stx2B in a mouse model. Ionotropic gelation via tripolyphosphate anions was used to coat Stx2B on chitosan. Subcutaneous injection or oral gavage was used to immunize mice, which were then challenged with E. coli O157:H7. Results: Immunity and protection against E. coli O157:H7 were achieved by all forms of the vaccine. Inactivated E. coli O157:H7 formulated with chitosan-coated Stx2B effectively evoked humoral and mucosal immune responses. However, minimum shedding appeared with the mice groups orally immunized with formalin-inactivated bacteria sublimated with chitosan-coated Stx2B and heat-inactivated bacteria plus Stx2B in subcutaneous immunization.Conclusion:Administration of inactivated whole-cell and toxin was synergistic and increased the protection capacity with both parenteral and oral immunization routes.

Oral rabies vaccination of dogs-Experiences from a field trial in Namibia.

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. To increase the herd immunity, free-roaming and stray dogs need to be specifically addressed in the vaccination campaigns, with oral rabies vaccination (ORV) of dogs being a possible solution. Using a third-generation vaccine and a standardized egg-flavoured bait, bait uptake and vaccination was assessed under field conditions in Namibia. During this trial, both veterinary staff as well as dog owners expressed their appreciation to this approach of vaccination. Of 1,115 dogs offered a bait, 90% (n = 1,006, 95%CI:91-94) consumed the bait and 72.9% (n = 813, 95%CI:70.2-75.4) of dogs were assessed as being vaccinated by direct observation, while for 11.7% (n = 130, 95%CI:9.9-17.7) the status was recorded as "unkown" and 15.4% (n = 172, 95%CI: 13.4-17.7) were considered as being not vaccinated. Smaller dogs and dogs offered a bait with multiple other dogs had significantly higher vaccination rates, while other factors, e.g. sex, confinement status and time had no influence. The favorable results of this first large-scale field trial further support the strategic integration of ORV into dog rabies control programmes. Given the acceptance of the egg-flavored bait under various settings worldwide, ORV of dogs could become a game-changer in countries, where control strategies using parenteral vaccination alone failed to reach sufficient vaccination coverage in the dog population.

HIV-1 Diversity and Drug Resistance in Treatment-Naïve Children and Adolescents from Rio de Janeiro, Brazil.

The human immunodeficiency virus type 1 (HIV-1) can be transmitted via parenteral, sexual, or vertical exposure routes. The number of HIV-1 cases detected yearly in children and adolescents in Brazil did not decrease over the last decade, representing ~5% of total cases described in the country. In recent years, the HIV-1 diversity and the prevalence of transmitted drug resistance mutations (TDRM) are moving toward a marked increase. In this study, we retrospectively evaluated the diversity of HIV-1 subtypes and the TDRM prevalence in 135 treatment-naïve HIV-1 vertically infected children and adolescents born in between 1993 and 2012. These children were assessed in either 2001–2007 or 2008–2012 when they were 0 to 17 years old. The individuals assessed in 2001–2007 (n = 38) had median CD4+ T cell counts of 1218 cells/mm3 (IQR: 738–2.084) and median HIV-1 plasma viral load of 4.18 log10 copies/mL (IQR: 3.88–4.08). The individuals (n = 97) evaluated in 2008–2012 showed median CD4+ T cell counts of 898.5 cells/mm3 (IQR: 591.3–1.821) and median HIV-1 plasma viral load of 4.69 log10 copies/mL (IQR: 4.26–5.33). A steady decrease in the median CD4 T+ cell counts was observed with age progression, as expected. The majority HIV-1 pol sequences (87%) were classified as pure HIV-1 subtypes (77% subtype B, 9% subtype F1 and 1.5% subtype C), while 13% of sequences were classified as recombinants (CRF45_cpx, n = 4; CRF28/29_BF1, n = 2; CRF02_AG, n = 1; CRF40_BF1, n = 1, CRF99_BF1, n = 1, URF_BF1, n = 8). The overall prevalence of TDRM was 14% (19/135), conferring resistance to the nucleoside reverse transcriptase inhibitors (NRTI, 13/135–9.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI, 8/135–5.9%), and protease inhibitors (PI, 2/135–1.5%). The main TDRM observed for NNRTI was the K103N (n = 8), while the mutations T215I/Y/D/E (n = 7) and M184V (n = 4) were the main TDRM for NRTI. Only two TDRM were observed for PI in one individual each (M46I and V82A). Most TDRM were found in the HIV-1 subtype B (84%) sequences. This study reveals an HIV-1 epidemic with high diversity and moderate prevalence of TDRM in the pediatric population of Rio de Janeiro, indicating the existence of possible problems in the clinical management of prophylactic therapy to prevent mother-to-child transmission and future treatment options for the affected children.

Setting impurity limits for endogenous substances: Recommendations for a harmonized procedure and an example using fatty acids

Endogenous substances, such as fatty, amino, and nucleic acids, are often purposefully used in parenterally pharmaceuticals, but may be present as impurities. Currently, no consensus guidance exists on setting impurity limits for these substances. Specific procedures are needed, as the amount and types of toxicity data available for endogenous substances are typically far less than those for other chemical impurities. Additionally, the parenteral route of administration of these substances is inherently non-physiological, resulting in potentially different or increased severity of toxicity. Risk Assessment Process Maps (RAPMAPs) are proposed as a model to facilitate the development of health-based exposure limits (HBELs) for endogenous substances. This yielded a framework that was applied to derive HBELs for several fatty acids commonly used in parenteral pharmaceuticals. This approach was used to derive HBELs with further vetting based on anticipated perturbations in physiological serum levels, impacts of dose-rate, and consideration of intermittent dosing. Parenteral HBELs of 100–500 mg/day were generated for several fatty acids, and a proposed class-based limit of 50 mg/day to be used in the absence of chemical-specific data. This default limit is consistent with the low toxicity of this chemical class and ICH Q3C value for Class 3 solvents.

A Overview on Nanosponges

The solid porous particles have a nanocavity structure in which drugs are encapsulated known as nanosponges. There are five types of nanosponges. Nanosponges size varies from 1um and less than 1 um. Nanosponges are stable at high temperatures. It has high drug loading capacity. Nanosponges formulation overcomes stability, delayed-release activity, and solubility-related problems. Nanosponges can deliver the drug through oral, parenteral, and topical routes. The current review focuses on nanosponges in drug delivery systems including their synthesis, characterization, and diverse applications.

Transenteric delivery of antibodies via an orally ingestible robotic pill yields high bioavailability comparable to parenteral administration in awake canines

Biotherapeutics such as peptides and antibodies are highly efficacious clinically but, unlike conventional medications, cannot be administered orally as they get digested and inactivated. Thus, biotherapeutics require parenteral routes for delivery, such as intravenous, intramuscular or subcutaneous administration. However, these delivery methods have limitations such as poor patient compliance or may require clinical supervision compared to oral therapies. We explored whether a novel, orally administered transenteric delivery system (Robotic Pill) could provide equivalent bioavailability to parenterally administered drugs. Utilizing an awake canine model, we demonstrated that orally administered Robotic Pills containing either human IgG or an anti-cytokine monoclonal antibody directed against either TNFα or interleukin-17A yielded bioavailability equivalent to parenterally administered controls. The ability to achieve clinically relevant blood levels of biotherapeutics via any orally administered preparation represents an important advance in drug delivery.

Neglected Comorbidity of Chronic Heart Failure: Iron Deficiency.

Iron deficiency is a significant comorbidity of heart failure (HF), defined as the inability of the myocardium to provide sufficient blood flow. However, iron deficiency remains insufficiently detected. Iron-deficiency anemia, defined as a decrease in hemoglobin caused by iron deficiency, is a late consequence of iron deficiency, and the symptoms of iron deficiency, which are not specific, are often confused with those of HF or comorbidities. HF patients with iron deficiency are often rehospitalized and present reduced survival. The correction of iron deficiency in HF patients is associated with improved functional capacity, quality of life, and rehospitalization rates. Because of the inflammation associated with chronic HF, which complicates the picture of nutritional deficiency, only the parenteral route can bypass the tissue sequestration of iron and the inhibition of intestinal iron absorption. Given the negative impact of iron deficiency on HF progression, the frequency and financial implications of rehospitalizations due to decompensation episodes, and the efficacy of this supplementation, screening for this frequent comorbidity should be part of routine testing in all HF patients. Indeed, recent European guidelines recommend screening for iron deficiency (serum ferritin and transferrin saturation coefficient) in all patients with suspected HF, regular iron parameters assessment in all patients with HF, and intravenous iron supplementation in symptomatic patients with proven deficiency. We thus aim to summarize all currently available data regarding this common and easily improvable comorbidity.

Antimicrobial Utilization among Neonates and Children: A Multicenter Point Prevalence Study from Leading Children's Hospitals in Punjab, Pakistan.

Antimicrobial resistance (AMR) compromises global health due to the associated morbidity, mortality, and costs. The inappropriate use of antimicrobial agents is a prime driver of AMR. Consequently, it is imperative to gain a greater understanding of current utilization patterns especially in high-risk groups including neonates and children. A point prevalence survey (PPS) was conducted among three tertiary care children’s hospitals in the Punjab province using the World Health Organization (WHO) methodology. Antibiotic use was documented according to the WHO AWaRe classification. Out of a total of 1576 neonates and children, 1506 were prescribed antibiotics on the day of the survey (prevalence = 95.5%), with an average of 1.9 antibiotics per patient. The majority of antibiotics were prescribed in the medical ward (75%), followed by surgical ward (12.8%). Furthermore, 56% of antibiotics were prescribed prophylactically, with most of the antibiotics (92.3%) administered via the parenteral route. The top three indications for antibiotics were respiratory tract infections (34.8%), gastrointestinal infections (15.8%), and prophylaxis for medical problems (14.3%). The three most common antibiotics prescribed were ceftriaxone (25.8%), amikacin (9.2%), and vancomycin (7.9%). Overall, 76.6% of the prescribed antibiotics were from Watch category followed by 21.6% from the Access group. There was a very high prevalence of antibiotic use among hospitalized neonates and children in this study. Urgent measures are needed to engage all the stakeholders to formulate effective ASPs in Pakistan, especially surrounding Watch antibiotics.

Clinical and immunological characteristics of opportunistic infections in children with the natural course of HIV infection, taking into account the route of infection

The purpose of the study is to improve the diagnosis and prognosis of opportunistic infections in children infected with HIV by vertical and parenteral routes, taking into account the dynamics of clinical and immunological parameters.Research methods. Clinical and laboratory examinations were carried out in 192 children infected with HIV by the vertical route (91; group I), parenteral route in infancy (44; group II) and over the age of one year (57; group III).Research results. In group I, a rapid development of immunosuppression was observed: mild immunodeficiency was diagnosed at the age of Me 4 (IQI 2—10) months, advanced immunodeficiency — Me 11 ( IQI 6—24.5) months, severe immunodeficiency — Me 23 ( IQI 11— 56) months. Clinical manifestation of opportunistic infections occurred in the first three years of life with a relatively high content of CD4-lymphocytes. Localized bacterial infections (Me 27,5; IQI 21,9–34,1/100 MYO), candidiasis (Me 14,1; IQI 10,2—18,9 / 100 MYO) and generalized infections (Me 5,2; IQI 2,9—8,5 / 100 MYO) had the highest relative incidence rate. In group II, there was a slower progression of immunosuppression (within one to seven years), the addition of opportunistic infections with a lower content of CD4-lymphocytes, in terms of one to nine years, a high relative incidence of herpes simplex infection (Me 12,9; IQI 7,8—14,9 / 100 MYO), herpes zoster (Me 3; IQI 1,5—5,4 / 100 MYO) and pneumocystosis (Me 3,8; IQI 2,1—6,4 / 100 MYO). In group III, there was a slow progression of immunosuppression (within one to eight years), the development of opportunistic infections with a low content of CD4-lymphocytes, in terms of two to ten years, a rarer manifestation of most diseases.Conclusion. These patterns should be taken into account when planning diagnostic, therapeutic and preventive measures in children with HIV infection, taking into account the path and age at the time of infection.

Detailed overview on pharmaceutical dosage forms in treatment of acne

Acne vulgaris is a skin condition characterized by an obstruction or inflammation of the oil glands, present on skin's surface, which are collectively termed as pilosebaceous units. The skin on face, back, and upper chest have a greater number of sebaceous follicles. Topical, systemic, or combination therapy can be used to treat acne, while mild and moderate acne are generally treated with topical therapy. Topical acne therapy has direct access to the target site (skin) prior to reaching the blood stream, thereby reducing the systemic adverse effects of delivery of drug via parenteral or oral routes. Oral antibiotics, on the other hand, are a crucial treatment for acne which have not improved with topical treatment and for inflammatory lesions, such as pustules, nodules, and papules. Due to their capability to improve dermal therapeutics by boosting therapeutic efficacy and lowering adverse effects, nanodelivery technologies, developed to address skin delivery difficulties, have been extensively investigated. The goal of this study is to go through the many types of pharmacological dosage forms that are available for the treatment of acne.

Vaccines, adjuvants and key factors for mucosal immune response.

Vaccines are the most effective tool to control infectious diseases, which provoke significant morbidity and mortality rates. Most vaccines are administered through the parenteral route and can elicit a robust systemic humoral response, but they induce a weak T-cell-mediated immunity and are poor inducers of mucosal protection. Considering that most pathogens enter the body through mucosal surfaces, a vaccine that elicits protection in the first site of contact between the host and the pathogen is promising. However, despite the advantages of mucosal vaccines as good options to confer protection on the mucosal surface, only a few mucosal vaccines are currently approved. In this review, we discuss the impact of vaccine administration in different mucosal surfaces; how appropriate adjuvants enhance the induction of protective mucosal immunity and other factors that can influence the mucosal immune response to vaccines.

Factors Limiting the Translatability of Rodent Model-Based Intranasal Vaccine Research to Humans.

The intranasal route of vaccination presents an attractive alternative to parenteral routes and offers numerous advantages, such as the induction of both mucosal and systemic immunity, needle-free delivery, and increased patient compliance. Despite demonstrating promising results in preclinical studies, however, few intranasal vaccine candidates progress beyond early clinical trials. This discrepancy likely stems in part from the limited predictive value of rodent models, which are used frequently in intranasal vaccine research. In this review, we explored the factors that limit the translatability of rodent-based intranasal vaccine research to humans, focusing on the differences in anatomy, immunology, and disease pathology between rodents and humans. We also discussed approaches that minimize these differences and examined alternative animal models that would produce more clinically relevant research.

Protective Efficacy of H9N2 Avian Influenza Vaccines Inactivated by Ionizing Radiation Methods Administered by the Parenteral or Mucosal Routes.

H9N2 viruses have become, over the last 20 years, one of the most diffused poultry pathogens and have reached a level of endemicity in several countries. Attempts to control the spread and reduce the circulation of H9N2 have relied mainly on vaccination in endemic countries. However, the high level of adaptation to poultry, testified by low minimum infectious doses, replication to high titers, and high transmissibility, has severely hampered the results of vaccination campaigns. Commercially available vaccines have demonstrated high efficacy in protecting against clinical disease, but variable results have also been observed in reducing the level of replication and viral shedding in domestic poultry species. Antigenic drift and increased chances of zoonotic infections are the results of incomplete protection offered by the currently available vaccines, of which the vast majority are based on formalin-inactivated whole virus antigens. In our work, we evaluated experimental vaccines based on an H9N2 virus, inactivated by irradiation treatment, in reducing viral shedding upon different challenge doses and compared their efficacy with formalin-inactivated vaccines. Moreover, we evaluated mucosal delivery of inactivated antigens as an alternative route to subcutaneous and intramuscular vaccination. The results showed complete protection and prevention of replication in subcutaneously vaccinated Specific Pathogen Free White Leghorn chickens at low-to-intermediate challenge doses but a limited reduction of shedding at a high challenge dose. Mucosally vaccinated chickens showed a more variable response to experimental infection at all tested challenge doses and the main effect of vaccination attained the reduction of infected birds in the early phase of infection. Concerning mucosal vaccination, the irradiated vaccine was the only one affording complete protection from infection at the lowest challenge dose. Vaccine formulations based on H9N2 inactivated by irradiation demonstrated a potential for better performances than vaccines based on the formalin-inactivated antigen in terms of reduction of shedding and prevention of infection.

SARS-CoV-2 Vaccines: The Mucosal Immunity Imperative

SARS-CoV-2 Vaccines: The Mucosal Immunity Imperative

Repeated subcutaneous racemic ketamine in treatment-resistant depression: case series.

Interest in the use of parenteral ketamine has been increasing over the last 2 decades for the management of treatment-resistant depression (TRD). While intravenous (IV) ketamine has been the most common parenteral route of administration, subcutaneous (SC) and intramuscular options have been described. We developed a clinical treatment protocol for the use of repeated SC racemic ketamine (maximum six treatments, twice per week) in an inpatient psychiatric care setting with inclusion/exclusion criteria, dosing schedule, and description of treatment, assessment, and monitoring procedures. Results from the first 10 consecutive patients demonstrated the effectiveness of SC racemic ketamine in relieving symptoms of TRD as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR 16 ). Response (≥50% reduction in scores from baseline to endpoint) was achieved in 8/10 cases on the MADRS and 6/10 on the QIDS-SR 16 . Remission was achieved in 8/10 (based on MADRS ≤10) and 5/10 (based on QIDS-SR 16 ≤6). Patients tolerated the treatments well with only transient blood pressure changes and dissociative side effects. Repeated SC ketamine treatments could be a safe, feasible, and effective alternative to IV ketamine infusions for patients with TRD.