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 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

scholarly journals Use of 30-Hz Accelerated iTBS in Drug-Resistant Unipolar and Bipolar Depression in a Public Healthcare Setting: A Case Series

2022 ◽  
Vol 12 ◽  
Author(s):  
Filippo Cantù ◽  
Giandomenico Schiena ◽  
Domenico Sciortino ◽  
Lorena Di Consoli ◽  
Giuseppe Delvecchio ◽  
...  
Keyword(s):  
Rating Scale ◽  
Bipolar Depression ◽  
Case Series ◽  
Healthcare Setting ◽  
Public Healthcare ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Depressive Episodes ◽  
Hamilton Rating Scale

Background: Depressive episodes, especially when resistant to pharmacotherapy, are a hard challenge to face for clinicians and a leading cause of disability worldwide. Neuromodulation has emerged as a potential therapeutic option for treatment-resistant depression (TRD), in particular transcranial magnetic stimulation (TMS). In this article, we present a case series of six patients who received TMS with an accelerated intermittent theta-burst stimulation (iTBS) protocol in a public healthcare setting.Methods: We enrolled a total number of six participants, affected by a treatment-resistant depressive episode, in either Major Depressive Disorder (MDD) or Bipolar Disorder (BD). Patients underwent an accelerated iTBS protocol, targeted to the left dorsolateral prefrontal cortex (DLPFC), 3-week-long, with a total of 6 days of overall stimulation. On each stimulation day, the participants received 3 iTBS sessions, with a 15-min pause between them. Patients were assessed by the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Anxiety (HAM-A), and the Mania Rating Scale (MRS). At baseline (T0), at the end of the second week (T1), and at the end of the cycle of stimulation (T2).Results: The rANOVA (repeated Analysis of Variance) statistics showed no significant effect of time on the rating scale scores, with a slight decrease in MADRS scores and a very slight increase in HAM-A and HAM-D scores. No manic symptoms emerged during the entire protocol.Conclusions: Although accelerated iTBS might be considered a less time-consuming strategy for TMS administration, useful in a public healthcare setting, our results in a real-word six-patient population with TRD did not show a significant effect. Further studies on wider samples are needed to fully elucidate the potential of accelerated iTBS protocols in treatment-resistant depression.

scholarly journals The Efficacy of Pramipexole, a Dopamine Receptor Agonist, as an Adjunctive Treatment in Treatment-Resistant Depression: An Open-Label Trial

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hiroaki Hori ◽  
Hiroshi Kunugi
Keyword(s):  
Rating Scale ◽  
Bipolar Depression ◽  
Care Facility ◽  
Adjunctive Treatment ◽  
Dopamine Receptor Agonist ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Serious Adverse Events ◽  
Resistant Depression

Dopaminergic dysfunction is implicated in the pathophysiology of treatment-resistant depression. Although the efficacy of adjunctive pramipexole treatment has been demonstrated in treatment-resistant bipolar depression, such data are scarce for major depressive disorder (MDD). We recruited 17 patients with DSM-IV major depressive episode who have failed to respond to previous treatment with a selective serotonin reuptake inhibitor. Five patients were diagnosed as having bipolar II disorder and 12 as having unipolar MDD. Patients were monitored at an ambulatory care facility every two weeks until 12 weeks. Pramipexole was added to existing medication. Depression severity was assessed with the Hamilton Depression Rating Scale 21-item version (HDRS-21). The mean maximum dosage of pramipexole was 1.6 mg (SD 0.9). The HDRS-21 total score decreased from 19.4 (SD 3.8) at baseline to 7.2 (SD 5.4) at endpoint (P<0.000001). Twelve patients (71%) were responders based on the definition of 50% or more reduction in the HDRS-21 score. Ten patients (59%) remitted (HDRS-21 total score at endpoint<8). These results were almost unchanged when the sample was confined to patients with MDD. No serious adverse events were observed. Our findings indicate that pramipexole augmentation therapy may be effective and well tolerated in refractory depressed patients.

Augmentation of Pharmacotherapy by Sleep Deprivation with Sleep Phase Advance in Treatment-Resistant Depression

2018 ◽  
Vol 52 (04) ◽  
pp. 186-192 ◽  
Author(s):  
Ewa Kurczewska ◽  
Ewa Ferensztajn-Rochowiak ◽  
Anna Jasińska-Mikołajczyk ◽  
Maria Chłopocka-Woźniak ◽  
Janusz K. Rybakowski
Keyword(s):  
Sleep Deprivation ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Interleukin 10 ◽  
Phase Advance ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Sleep Phase ◽  
Preliminary Study ◽  
Resistant Depression

Abstract Introduction The aim was to assess the efficacy of total sleep deprivation (TSD) with sleep phase advance (SPA) in treatment-resistant depression (TRD) and associated biochemical factors. Methods We studied nine males and 12 females, aged 49±14 years, with treatment-resistant unipolar or bipolar depression, receiving antidepressant and mood-stabilizing drugs. The four-day schedule included single TSD and three consecutive nights with SPA. Biochemical markers were measured on the day before and on 1st, 7th and 14th day after the TSD. Results Ten subjects met criteria for response, defined as a reduction of ≥50% in the Hamilton Depression Rating Scale, on the 14th day. Concentrations of cortisol at baseline were lower in responders, and they decreased during therapy in both groups. In responders, there was an increase of interleukin-10 (IL-10) and IL-1β on the 14th day. Discussion Our preliminary study demonstrated the efficacy of pharmacotherapy augmentation by TSD and SPA in half of the patients with TRD. The main biochemical factors related to clinical response included status of cortisol and increase in IL-10 and IL-1β levels.

scholarly journals A Double-Blind Pilot Dosing Study of Low Field Magnetic Stimulation (LFMS) for Treatment-Resistant Depression (TRD)

2018 ◽  
Author(s):  
Marc J. Dubin ◽  
Irena Ilieva ◽  
Zhi-De Deng ◽  
Jeena Thomas ◽  
Ashly Cochran ◽  
...  
Keyword(s):  
Magnetic Stimulation ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Double Blind ◽  
The Third ◽  
Low Field ◽  
Resistant Depression

AbstractLow Field Magnetic Stimulation is a potentially rapid-acting treatment for depression with mood-enhancing effects in as little as one 20-minute session. The most convincing data for LFMS has come from treating bipolar depression. We examined whether LFMS also has rapid mood-enhancing effects in treatment-resistant major depressive disorder, and whether these effects are dose-dependent. We hypothesized that a single 20-min session of LFMS would reduce depressive symptom severity and that the magnitude of this change would be greater after three 20-min sessions than after a single 20-min session. In a double-blind randomized controlled trial, 30 participants (age 21–65) with treatment-resistant depression were randomized to three 20-minute active or sham LFMS treatments with 48 hours between treatments. Response was assessed immediately following LFMS treatment using the 6-item Hamilton Depression Rating Scale (HAMD-6), the Positive and Negative Affect Scale (PANAS) and the Visual Analog Scale. Following the third session of LFMS, the effect of LFMS on VAS and HAMD-6 was superior to sham (F(1, 24) = 7.45, p = 0.03, Holm-Bonferroni corrected; F(1,22) = 6.92, p = 0.03, Holm-Bonferroni corrected, respectively). There were no differences between sham and LFMS following the initial or second session with the effect not becoming significant until after the third session. Three 20-minute LFMS sessions were required for active LFMS to have a mood-enhancing effect for individuals with treatment-resistant depression. As this effect may be transient, future work should address dosing schedules of longer treatment course as well as biomarker-based targeting of LFMS to optimize patient selection and treatment outcomes.

scholarly journals Prevalence and Impact of Treatment-Resistant Depression in Latin America: a Prospective, Observational Study

2021 ◽  
Author(s):  
Bernardo Soares ◽  
Gabriela Kanevsky ◽  
Chei Tung Teng ◽  
Rodrigo Pérez-Esparza ◽  
Gerardo Garcia Bonetto ◽  
...  
Keyword(s):  
Latin America ◽  
Observational Study ◽  
Latin American ◽  
Prospective Observational Study ◽  
Rating Scale ◽  
Fisher Exact Test ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Work Impairment ◽  
Resistant Depression

AbstractApproximately one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD). The TRAL study will evaluate the prevalence and impact of TRD among patients with MDD in four Latin American countries. In this multicenter, prospective, observational study, patients with MDD were recruited from 33 reference sites in Mexico, Colombia, Brazil, and Argentina. Patients were assessed for TRD, defined as failure to respond to ≥ 2 antidepressant medications of adequate dose and duration. Demographics, previous/current treatments, depressive symptoms, functioning, healthcare resource utilization, and work impairment were also collected and evaluated using descriptive statistics, chi-square test, Fisher exact test, t-test for independent samples, or the Mann–Whitney nonparametric test, as appropriate. 1475 patients with MDD were included in the analysis (mean age, 45.6 years; 78% women); 89% were receiving relevant psychiatric treatment. 429 patients met criteria for TRD, and a numerically higher proportion of patients with TRD was present in public versus private sites of care (31% vs 27%). The mean Montgomery-Asberg Depression Rating Scale score was 25.0 among all MDD patients and was significantly higher for patients with TRD versus non-TRD (29.4 vs 23.3; P < 0.0001). Patients with TRD, versus those with non-TRD, were significantly more likely to be older, have a longer disease duration, have more comorbidities, be symptomatic, have a higher median number of psychiatric consultations, and report greater work impairment. Patients with TRD have a disproportionate burden of disease compared to those with non-TRD. Appropriate treatment for TRD is a substantial unmet need in Latin America. https://www.ClinicalTrials.gov identifier NCT03207282, 07/02/2017.

scholarly journals Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

2018 ◽  
Vol 49 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C. Andrade ◽  
Morgana M. Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractBackgroundRecent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.MethodsTo test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.ResultsWe observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p= 0.04), and at D7 (p< 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64%v.27%;p= 0.04). Remission rate showed a trend toward significance at D7 (36%v.7%,p= 0.054).ConclusionsTo our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered athttp://clinicaltrials.gov(NCT02914769).

Esketamine: A Novel Option for Treatment-Resistant Depression

2019 ◽  
Vol 54 (6) ◽  
pp. 567-576 ◽  
Author(s):  
Kevin M. Bozymski ◽  
Ericka L. Crouse ◽  
Erika N. Titus-Lay ◽  
Carol A. Ott ◽  
Jill L. Nofziger ◽  
...  
Keyword(s):  
English Language ◽  
Rating Scale ◽  
Data Extraction ◽  
Fixed Dose ◽  
Depression Symptoms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Pubmed Search ◽  
Resistant Depression ◽  
Suicidal Thoughts And Behaviors

Objective:To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine, and JNJ-54135419. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (−4.1; 95% CI = −7.69 to −0.49; P = 0.027 [exploratory]) and flexible-dosed arms (−4.0; 95% CI = −7.31 to −0.64; P = 0.02), though the fixed-dose 84-mg arm (−3.2; 95% CI = −6.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (−3.6; 95% CI = −7.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine’s adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine’s role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.

scholarly journals Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression

2019 ◽  
Vol 91 (2) ◽  
pp. 189-195 ◽  
Author(s):  
Junus M. van der Wal ◽  
Isidoor O. Bergfeld ◽  
Anja Lok ◽  
Mariska Mantione ◽  
Martijn Figee ◽  
...  
Keyword(s):  
Rating Scale ◽  
Response Rate ◽  
Internal Capsule ◽  
Maintenance Phase ◽  
Efficacy And Safety ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Deep Brain

ObjectiveDeep brain stimulation (DBS) reduces depressive symptoms in approximately 40%–60% of patients with treatment-resistant depression (TRD), but data on long-term efficacy and safety are scarce. Our objective was to assess the efficacy and safety of DBS targeted at the ventral anterior limb of the internal capsule (vALIC) in 25 patients with TRD during a 1-year, open-label, maintenance period, which followed a 1-year optimisation period.MethodsDepression severity was measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Montgomery-Asberg Depression Rating Scale (MADRS) and self-reported Inventory of Depressive Symptomatology (IDS-SR). Primary outcomes were response rate (≥50% HAM-D-17 score reduction) after the maintenance phase, approximately 2 years after DBS surgery, and changes in depression scores and occurrence of adverse events during the maintenance phase.ResultsOf 25 operated patients, 21 entered and 18 completed the maintenance phase. After the maintenance phase, eight patients were classified as responder (observed response rate: 44.4%; intention-to-treat: 32.0%). During the maintenance phase, HAM-D-17 and MADRS scores did not change, but the mean IDS-SR score decreased from 38.8 (95% CI 31.2 to 46.5) to 35.0 (95% CI 26.1 to 43.8) (p=0.008). Non-responders after optimisation did not improve during the maintenance phase. Four non-DBS-related serious adverse events occurred, including one suicide attempt.ConclusionsvALIC DBS for TRD showed continued efficacy 2 years after surgery, with symptoms remaining stable after optimisation as rated by clinicians and with patient ratings improving. This supports DBS as a viable treatment option for patients with TRD.Trial registration numberNTR2118.

scholarly journals Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data

2020 ◽  
Vol 23 (7) ◽  
pp. 426-433 ◽  
Author(s):  
Michel Nijs ◽  
Ewa Wajs ◽  
Leah Aluisio ◽  
Ibrahim Turkoz ◽  
Ella Daly ◽  
...  
Keyword(s):  
Nasal Spray ◽  
Rating Scale ◽  
Maintenance Phase ◽  
Induction Phase ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Treatment Frequency ◽  
Resistant Depression ◽  
The Impact

Abstract Background Esketamine nasal spray was recently approved for treatment-resistant depression. The current analysis evaluated the impact of symptom-based treatment frequency changes during esketamine treatment on clinical outcomes. Methods This is a post-hoc analysis of an open-label, long-term (up to 1 year) study of esketamine in patients with treatment-resistant depression (SUSTAIN 2). During a 4-week induction phase, 778 patients self-administered esketamine twice weekly plus a new oral antidepressant daily. In responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale total score from baseline), esketamine treatment frequency was thereafter decreased during an optimization/maintenance phase to weekly for 4 weeks and then adjusted to the lowest frequency (weekly or every other week) that maintained remission (Montgomery-Åsberg Depression Rating Scale ≤ 12) based on a study-defined algorithm. The relationship between treatment frequency and symptom response, based on clinically meaningful change in Clinical Global Impression–Severity score, was subsequently evaluated 4 weeks after treatment frequency adjustments in the optimization/maintenance phase. Results Among 580 responders treated with weekly esketamine for the first 4 weeks in the optimization/maintenance phase (per protocol), 26% continued to improve, 50% maintained clinical benefit, and 24% worsened. Thereafter, when treatment frequency could be reduced from weekly to every other week, 19% further improved, 49% maintained benefit, and 32% worsened. For patients no longer in remission after treatment frequency reduction, an increase (every other week to weekly) resulted in 47% improved, 43% remained unchanged, and 10% worsened. Conclusions These findings support individualization of esketamine nasal spray treatment frequency to optimize treatment response in real-world clinical practice. Trial Registration ClinicalTrials.gov identifier: NCT02497287

Sign in / Sign up

Export Citation Format

Share Document