scholarly journals Somatic Comorbidities and Cardiovascular Safety in Ketamine Use for Treatment-Resistant Depression

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 274
Author(s):  
Joanna Szarmach ◽  
Wiesław Jerzy Cubała ◽  
Adam Włodarczyk ◽  
Maria Gałuszko-Węgielnik
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Heart Rate ◽  
Small Sample ◽  
Tolerability Profile ◽  
Acute Administration ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Somatic Comorbidities ◽  
Resistant Depression

Background and Objectives: There is evidence for ketamine efficacy in treatment-resistant depression (TRD). Several safety and tolerability concerns arise that some psychotropic agents may provide blood pressure or/and heart rate alterations. The aim of this study is to review blood pressure measurements in course of the treatment with ketamine on treatment refractory inpatients with somatic comorbidities in the course of MDD and BP. Materials and Methods: The study population of 49 patients comprised MDD and BP subjects treated with ketamine registered in the naturalistic observational protocol of treatment-resistant mood disorders (NCT04226963). Results: The conducted analysis showed that among people suffering from hypertension there is a higher increase in systolic blood pressure (RR) after infusion 2 (p = 0.004) than among people who do not suffer from hypertension. Patients with hypertension have a higher increase in diastolic RR compared to those not suffering from hypertension (p = 0,038). Among the subjects with diabetes mellitus, significant differences occurred for infusions 2 (p = 0.020), 7 (p = 0.020), and 8 (p = 0.035) for heart rate (HR), compared to subjects without diabetes mellitus. A higher increase in diastolic RR was noted in the group of subjects suffering from diabetes mellitus (p = 0.010) compared to those who did not. In the hyperlipidemic patients studied, a significantly greater decrease in HR after infusion 5 (p = 0.031) and systolic RR after infusion 4 (p = 0.036) was noted compared to nonpatients. People after a stroke had significantly higher increases in diastolic RR after infusions 4 (p = 0.021) and 6 (p = 0.001) than those who did not have a stroke. Patients suffering from epilepsy had a significantly greater decrease in systolic RR after the 8th infusion (p = 0.017) compared to those without epilepsy. Limitations: The study may be underpowered due to the small sample size. The observations apply to inhomogeneous TRD population in a single-site with no blinding and are limited to the acute administration. Conclusions: This study supports evidence for good safety and tolerability profile for short-term IV ketamine use in TRD treatment. However, risk mitigation measures are to be considered in patients with metabolic and cardiovascular comorbidities.

scholarly journals Ketamine treatment safety in treatment-resistant depression with somatic comorbidities: focus on dissociation and psychotic symptomatology.

2021 ◽  
Author(s):  
Adam Włodarczyk ◽  
Wiesław J. Cubała ◽  
Maria Węgielnik-Gałuszko ◽  
Mariusz S. Wiglusz
Keyword(s):  
Clinical Supervision ◽  
Small Sample ◽  
Psychotic Symptoms ◽  
Acute Administration ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Somatic Comorbidity ◽  
Somatic Comorbidities ◽  
Resistant Depression ◽  
Patients With Epilepsy

Abstract Background and objectives: There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety concerns arise regarding adverse drug reactions and specific subpopulations. The aim of this paper is to investigate the safety of intravenous ketamine treatment concerning dissociative and psychotic measures in TRD inpatients with Major Depressive Disorder (MDD) and Bipolar depression (BP) with somatic comorbidities.Methods: The study population of forty-nine inpatients comprises of MDD and BP subjects treated with ketamine registered in the naturalistic observational protocol of the tertiary reference unit for mood disorders (NCT04226963). This dataset represents an intermittent analysis of an observational study performed for interim modelling of observational learning. The study may be underpowered due to the small sample size. The observations apply to the inhomogeneous TRD population in a single-site with no blinding and are limited to the acute administration. Results: The epilepsy was significantly associated with changes in BPRS over time (p=0.008). Psychotic symptomatology with BPRS scores for comorbid somatic conditions excluding epilepsy turned out to be insignificant (p = 0.198) regardless of the diagnosis. However, for a subgroup of patients with epilepsy substantial fluctuation was seen across all administrations in the time course of the study. Conclusions: In ketamine use, careful consideration of comorbidities and concomitant medication is needed. In ketamine administration, close-clinical supervision is necessary at every visit. Psychotic symptoms must be taken into consideration in planning treatment with TRD patients with epilepsy. Somatic comorbidity may impact dissociative symptomatology. Trial Registration: Study registered: 04DEC2019, clinicaltrials.com no. NCT04226963 https://clinicaltrials.gov/ct2/show/NCT04226963

Effects of subcutaneous esketamine on blood pressure and heart rate in treatment-resistant depression

2020 ◽  
Vol 34 (10) ◽  
pp. 1155-1162
Author(s):  
Lorena Catarina Del Sant ◽  
Luciana Maria Sarin ◽  
Eduardo Jorge Muniz Magalhães ◽  
Ana Cecília Lucchese ◽  
Marco Aurélio Tuena ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Vital Signs ◽  
Response To Treatment ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Post Dose ◽  
Before And After ◽  
Resistant Depression ◽  
The Impact

Introduction and objectives: The impact of multiple subcutaneous (s.c.) esketamine injections on the blood pressure (BP) and heart rate (HR) of patients with unipolar and bipolar treatment-resistant depression (TRD) is poorly understood. This study aimed to assess the cardiovascular safety of multiple s.c. doses of esketamine in patients with TRD. Methods: Seventy TRD patients received 394 weekly s.c. esketamine injections in conjunction with oral antidepressant therapy for up to six weeks. Weekly esketamine doses were 0.5, 0.75 or 1.0 mg/kg according to each patient’s response to treatment. Participants were monitored before each treatment and every 15 minutes thereafter for 120 minutes. We assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measurements for the entire treatment course. Results: BP increased after the first s.c. esketamine injection, reaching maximum mean SBP/DBP levels of 4.87/5.54 mmHg within 30–45 minutes. At the end of monitoring, 120 minutes post dose, vital signs returned to pretreatment levels. We did not detect significant differences in BP between doses of 0.5, 0.75, and 1 mg/kg esketamine. Mean HR did not differ significantly between doses or before and after s.c. esketamine injection. Conclusions: The BP changes observed with repeated s.c. esketamine injections were mild and well tolerated for doses up to 1 mg/kg. The s.c. route is a simple and safe method of esketamine administration, even for patients with clinical comorbidities, including obesity, hypertension, diabetes, and dyslipidemia. However, 14/70 patients experienced treatment-emergent transient hypertension (SBP >180 mmHg and/or a DBP >110 mmHg). Therefore, we strongly recommend monitoring BP for 90 minutes after esketamine dosing. Since s.c. esketamine is cheap, requires less frequent dosing (once a week), and is a simpler procedure compared to intravenous infusions, it might have an impact on public health.

scholarly journals Ketamine treatment safety and tolerability in treatment-resistant depression with somatic comorbidities: focus on dissociation and psychotic symptomatology.

2020 ◽  
Author(s):  
Adam Włodarczyk ◽  
Wiesław J. Cubała ◽  
Maria Węgielnik-Gałuszko ◽  
Mariusz S. Wiglusz
Keyword(s):  
Clinical Supervision ◽  
Bipolar Depression ◽  
Small Sample Size ◽  
Small Sample ◽  
Psychotic Symptoms ◽  
Acute Administration ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Somatic Comorbidity ◽  
Resistant Depression

Abstract Background and objectives: There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety and tolerability concerns arise regarding adverse drug reactions and specific subpopulations. The aim of this paper is to investigate the relationship between dissociative and psychometric measures in course of intravenous ketamine treatment in TRD inpatients with Major Depressive Disorder and Bipolar depression.Methods: The study population of 49 inpatients comprises of MDD and BP subjects treated with ketamine registered in the naturalistic observational protocol of the tertiary reference unit for mood disorders (NCT04226963). The study may be underpowered due to the small sample size. The observations apply to inhomogeneous TRD population in a single-site with no blinding and are limited to the acute administration. Results: The epilepsy was significantly associated with changes in BPRS over time (p=0.008). Psychotic symptomatology with BPRS scores for comorbid somatic conditions excluding epilepsy turned out to be insignificant (p = 0.198) regardless the diagnosis. Conclusions: In ketamine use, careful consideration of comorbidities and concomitant medication is needed. In ketamine administration close-clinical supervision is necessary at every visit. Psychotic symptoms must be taken into consideration in planning treatment with TRD patients with epilepsy. Somatic comorbidity may impact dissociative symptomatology. Trial Registration: Study registered: 04DEC2019, clinicaltrials.com no. NCT04226963 https://clinicaltrials.gov/ct2/show/NCT04226963

Intranasal esketamine: A novel drug for treatment-resistant depression

2020 ◽  
Vol 77 (17) ◽  
pp. 1382-1388
Author(s):  
Farah Khorassani ◽  
Om Talreja
Keyword(s):  
Blood Pressure ◽  
English Language ◽  
Severe Depression ◽  
Antidepressant Therapy ◽  
Inadequate Response ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Included Review ◽  
Resistant Depression ◽  
Novel Drug

Abstract Purpose To review the efficacy, safety, and place in therapy of intranasal esketamine, a treatment modality for treatment-resistant depression. Summary An electronic literature search of PubMed, MEDLINE, and the ClinicalTrials.gov and Food and Drug Administration (FDA) websites covering the period April 2015 through June 2020 was performed using the following search terms: esketamine, intranasal esketamine, depression, and treatment-resistant depression. Other resources included review articles and the manufacturer’s product labeling. All relevant English-language articles and reports on clinical trials conducted in humans were included. Esketamine (Spravato, Janssen Pharmaceuticals) is an intranasal antidepressant approved by FDA for management of treatment-resistant depression (TRD) in patients with inadequate response to traditional antidepressant therapy. Esketamine is self-administered under the supervision of a healthcare provider and is used as an adjunct to oral antidepressant therapy. Patients are supervised for 2 hours after self-administering the medication to monitor for sedation, dizziness, dissociation reactions, and increased blood pressure. Esketamine has a favorable risk-to-benefit profile, with demonstrated efficacy in reducing depressive symptoms more rapidly than monotherapy with traditional oral antidepressants. Reported adverse effects include sedation, dizziness, dissociation reactions, and blood pressure elevations, but these effects are primarily confined to the 2-hour postdose monitoring window. Conclusion Patients with moderate to severe depression who are not sufficiently responsive to traditional strategies for managing TRD may benefit from adjunctive esketamine therapy.

scholarly journals Diminished responses to monoaminergic antidepressants but not ketamine in a mouse model for neuropsychiatric lupus

2018 ◽  
Vol 33 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Bettadapura N Srikumar ◽  
Pattipati S Naidu ◽  
Narasimharaju Kalidindi ◽  
Mahesh Paschapur ◽  
Bharath Adepu ◽  
...  
Keyword(s):  
Wheel Running ◽  
Forced Swim Test ◽  
Sucrose Preference ◽  
Acute Administration ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time ◽  
Resistant Depression

Background: A significant proportion of patients suffering from major depression fail to remit following treatment and develop treatment-resistant depression. Developing novel treatments requires animal models with good predictive validity. MRL/lpr mice, an established model of systemic lupus erythematosus, show depression–like behavior. Aims: We evaluated responses to classical antidepressants, and associated immunological and biochemical changes in MRL/lpr mice. Methods and results: MRL/lpr mice showed increased immobility in the forced swim test, decreased wheel running and sucrose preference when compared with the controls, MRL/MpJ mice. In MRL/lpr mice, acute fluoxetine (30 mg/kg, intraperitoneally (i.p.)), imipramine (10 mg/kg, i.p.) or duloxetine (10 mg/kg, i.p.) did not decrease the immobility time in the Forced Swim Test. Interestingly, acute administration of combinations of olanzapine (0.03 mg/kg, subcutaneously)+fluoxetine (30 mg/kg, i.p.) or bupropion (10 mg/kg, i.p.)+fluoxetine (30 mg/kg, i.p.) retained efficacy. A single dose of ketamine but not three weeks of imipramine (10 mg/kg, i.p.) or escitalopram (5 mg/kg, i.p.) treatment in MRL/lpr mice restored sucrose preference. Further, we evaluated inflammatory, immune-mediated and neuronal mechanisms. In MRL/lpr mice, there was an increase in autoantibodies’ titers, [3H]PK11195 binding and immune complex deposition. There was a significant infiltration of the brain by macrophages, neutrophils and T-lymphocytes. p11 mRNA expression was decreased in the prefrontal cortex. Further, there was an increase in the 5-HT2aR expression, plasma corticosterone and indoleamine 2,3-dioxygenase activity. Conclusion: In summary, the MRL/lpr mice could be a useful model for Treatment Resistant Depression associated with immune dysfunction with potential to expedite antidepressant drug discovery.

Rumination-focused cognitive behaviour therapy for non-responsive chronic depression: an uncontrolled group study

2019 ◽  
Vol 48 (3) ◽  
pp. 376-381
Author(s):  
Stine Bjerrum Moeller ◽  
Stephen F. Austin ◽  
Morten Hvenegaard ◽  
Morten Kistrup ◽  
Stine Gran ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Small Sample ◽  
Post Treatment ◽  
Chronic Depression ◽  
Hamilton Depression Scale ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Cognitive Behaviour ◽  
Resistant Depression

AbstractBackground:One-third of patients with depression do not respond satisfactorily to treatment, and approximately 20% of all patients treated for depression develop a chronic depression. One approach to more effective treatment of chronic and treatment-resistant depression is to target rumination – an underlying mechanism implicated in the development and maintenance of depression.Aim:The purpose of this uncontrolled group study was to investigate the feasibility of individual rumination-focused cognitive behavioural therapy (RfCBT) for patients with chronic and treatment-resistant depression.Method:A total of 10 patients with chronic and treatment-resistant depression were offered 12–16 individual sessions of RfCBT. The primary outcome was depressive symptoms as measured by Hamilton Depression Scale at pre-, post- and 3-month follow-up. Secondary symptoms measured included self-reported rumination and worry.Results:There was a significant reduction in depressive symptoms (p < 0.05), rumination (p < 0.01) and worry (p < 0.5) from pre- to post-treatment. Half of the participants (n = 5) showed significant reliable change on levels of depressive symptoms post-treatment. The reduction in depressive symptoms, rumination and worry were maintained at follow-up.Conclusions:RfCBT was associated with significant reductions in depressive symptoms in a small sample with chronic and treatment-resistant depression. Despite limitations of being a small uncontrolled study with limited follow-up, these results are promising in a difficult to treat population. RfCBT warrants further systematic evaluation.

scholarly journals Central nervous system-related safety and tolerability of add-on ketamine to antidepressant medication in treatment-resistant depression: focus on the unique safety profile of bipolar depression

2021 ◽  
Vol 11 ◽  
pp. 204512532110110
Author(s):  
Adam Włodarczyk ◽  
Wiesław J. Cubała ◽  
Maria Gałuszko-Węgielnik ◽  
Joanna Szarmach
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Small Sample Size ◽  
Small Sample ◽  
Mood Stabilizers ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

Background: There is evidence supporting the use of ketamine in treatment-resistant depression (TRD). However, there are some safety and tolerability concerns associated with ketamine. This study aimed to investigate ketamine’s safety and tolerability to the central nervous system and to assess the relationship between dissociative symptomology and psychometric outcomes during and after intravenous ketamine treatment concurrent with treatment by varying psychotropic medications in treatment-refractory inpatients with major depressive disorder (MDD) and bipolar disorder (BP). Methods: A total of 49 patients with MDD and BP were included in this study. The subjects were administered ketamine and were assessed for changes using an observational protocol. Results: No antidepressants were associated with psychomimetic symptomatology except for citalopram ( p = 0.019). Patients treated with citalopram showed a higher intensity of psychomimetic symptomatology. The use of classic mood-stabilizers was significantly associated with an increase in psychomimetic symptomatology according to the Brief Psychiatric Rating Scale (BPRS; lamotrigine p = 0.009, valproate p = 0.048, lithium p = 0.012). No sequelae were observed. Conclusions: Despite the limitations that this study may be underpowered due to the small sample size, the sample consisted of a heterogeneous TRD population in a single site, and there no blinding of who underwent only acute ketamine administration, our observations indicate ketamine use requires close safety and tolerability monitoring with regards to psychomimetic and dissociative symptoms in TRD-BP and careful management for MDD patients. ClinicalTrials.gov identifier: NCT04226963

scholarly journals Excess deaths in treatment-resistant depression

2021 ◽  
Vol 11 ◽  
pp. 204512532110065
Author(s):  
Philip Brenner ◽  
Johan Reutfors ◽  
Michel Nijs ◽  
Therese M-L Andersson
Keyword(s):  
Mortality Risk ◽  
Survival Models ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Somatic Comorbidities ◽  
Comorbidity Index ◽  
Resistant Depression ◽  
External Causes ◽  
Parametric Survival ◽  
Excess Deaths

Background: Patients with treatment-resistant depression (TRD) have an increased mortality risk compared with other patients with depression, but it is not known how this translates into absolute numbers of excess deaths. Methods: Swedish national registers were used to identify a cohort of 118,774 antidepressant initiators 18–69 years old with a depression diagnosis. Patients who initiated a third consecutive treatment trial were classified as having TRD. Flexible parametric survival models were used to estimate the mortality risk due to all causes and external causes (suicides and accidents), comparing TRD patients with patients with other depression while adjusting for clinical and sociodemographic covariates and including interactions with TRD, age, and Charlson comorbidity index (CCI) for a number of somatic comorbidities. Standardized survival was estimated, as were numbers of excess deaths among TRD patients within each age and comorbidity category. Results: Compared with the mortality risk of other depressed patients, patients with TRD experienced excess deaths in most age and comorbidity categories in the range of 7–16 deaths per 1000 patients during 5 years. Highest numbers for all-cause excess deaths were found among patients 18–29 years old with CCI 1, where 16 [95% confidence interval 5–28] of the expected 37 [25–48] deaths per 1000 patients were excess deaths. The majority of the excess deaths were due to external causes. Conclusion: Patients with TRD experience significant numbers of excess deaths compared with other patients with depression.

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