Depression treatment response to ketamine: sex-specific role of interleukin-8, but not other inflammatory markers

AbstractInflammation plays a role in depression pathophysiology and treatment response, with effects varying by sex and therapeutic modality. Lower levels of interleukin(IL)-8 predict depression response to antidepressant medication and to electroconvulsive therapy (ECT), although ECT effects are specific to females. Whether IL-8 predicts depression response to ketamine and in a sex-specific manner is not known. Here, depressed patients (n = 46; female, n = 17) received open label infusion of ketamine (0.5 mg/kg over 40 min; NCT02165449). Plasma levels of IL-8 were evaluated at baseline and post-treatment. Baseline levels of IL-8 had a trending association with response to ketamine, depending upon sex (responder status × sex interaction: p = 0.096), in which lower baseline levels of IL-8 in females (p = 0.095) but not males (p = 0.96) trended with treatment response. Change in levels of IL-8 from baseline to post-treatment differed significantly by responder status (defined as ≥50% reduction in Hamilton Depression Rating Scale [HAM-D] Score), depending upon sex (responder status × sex × time interaction: F(1,42)=6.68, p = 0.01). In addition, change in IL-8 interacted with sex to predict change in HAM-D score (β = -0.63, p = 0.003); increasing IL-8 was associated with decreasing HAM-D score in females (p = 0.08) whereas the inverse was found in males (p = 0.02). Other inflammatory markers (IL-6, IL-10, tumor necrosis factor-α, C-reactive protein) were explored with no significant relationships identified. Given these preliminary findings, further evaluation of sex differences in the relationship between IL-8 and treatment response is warranted to elucidate mechanisms of response and aid in the development of personalized approaches to depression treatment.

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An exploratory study of adolescent response to fluoxetine using psychological and biological predictors

PeerJ ◽

10.7717/peerj.4240 ◽

2018 ◽

Vol 6 ◽

pp. e4240 ◽

Cited By ~ 1

Author(s):

Ada H. Zohar ◽

Tamar Eilat ◽

Maya Amitai ◽

Michal Taler ◽

Romi Bari ◽

...

Keyword(s):

Treatment Response ◽

Exploratory Study ◽

Psychiatric Morbidity ◽

Binary Logistic Regression ◽

Primary Diagnosis ◽

Type D Personality ◽

Post Treatment ◽

Open Label ◽

Type D ◽

And Biological Markers

BackgroundNot enough is known about predicting therapeutic response to serotonin-specific reuptake inhibitors, and specifically to fluoxetine. This exploratory study used psychological and biological markers for (retrospective) prediction of treatment-response to fluoxetine in depressed and/or anxious adolescents.MethodsForty-one consecutive adolescent outpatients with a primary diagnosis of severe affective and/or anxiety disorders were assessed and treated with an open-label 8-week trial of fluoxetine. Type D personality was assessed with the 14-item questionnaire, the DS14. In addition, TNFα, IL-6, and IL-1b were measured pre- and post-treatment.ResultsThere was an elevation of Type D personality in patients, compared to the adolescent population rate. Post-treatment, 44% of patients were classified as non-responders; the relative risk of non-response for Type D personality patients was 2.8. Binary logistic regression predicting response vs. non-response showed a contribution of initial TNFα levels as well as Type D personality to non-response.ConclusionsIn this exploratory study, the most significant contributor to non-response was Type D personality. However, the measurement of Type D was not prospective, and thus may be confounded with psychiatric morbidity. The measurement of personality in psychiatric settings may contribute to the understanding of treatment response and have clinical utility.

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A-148 Executive Dysfunction in Late-Life Depression: Changes and Relationship to Treatment Response in a Clinical Trial

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.166 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1202-1202

Author(s):

Matthew S Schurr ◽

George S Alexopoulos ◽

Patricia A Arean ◽

Patrick J Raue ◽

Brenna N Renn

Keyword(s):

Executive Functioning ◽

Treatment Response ◽

Iowa Gambling Task ◽

Rating Scale ◽

Late Life ◽

Executive Dysfunction ◽

Post Treatment ◽

World Health ◽

Late Life Depression ◽

Treatment Changes

Abstract Objective Executive dysfunction is the core neurocognitive deficit associated with late-life depression (LLD). This study identified changes in executive functioning during a structured behavioural treatment for depression in older adults and ascertained if pre-treatment executive dysfunction predicted treatment response. Method We analyzed data from a large multisite randomized controlled trial of structured behavioral psychotherapies (PST and Engage) for unipolar depression in adults ≥60 years. Participants were diagnosed with major depressive disorder and had Mini-Mental State Examination [MMSE] ≥24. Cognitive measures included the Stroop test, digit span, Iowa Gambling Task (IGT), and Wisconsin Card Sorting Test (WCST). Treatment response outcomes included pre- to post-treatment changes on the Hamilton Depression Rating Scale (HAM-D) and World Health Organization Disability Assessment Schedule II (WHODAS-II). One-way analysis of variance (ANOVA) assessed pre- and post-treatment changes in executive functioning measures across 9 weeks of treatment for 95 participants with complete data. Multiple linear regression models tested whether baseline measures of executive functioning predicted treatment response in (a) HAM-D depression and (b) WHODAS disability scores. Results A one-way ANOVA revealed improvements on IGT performance (Total Money) between baseline and week 9 post-treatment (F(1,186) = 7.00, p < 0.01). No combination of baseline measures of executive functioning significantly predicted change in HAM-D or WHODAS scores across treatment (ps > 0.05). Conclusion Baseline executive functioning did not predict treatment response (change in depressive symptoms or disability ratings). That is, individuals improved on treatment outcomes regardless of baseline executive dysfunction. In addition, results suggest that these approaches may actually improve real-life decision-making.

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QOLP-16. EFFICACY OF SCRAMBLER THERAPY (CALMARE®) FOR THE TREATMENT OF CHRONIC CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.741 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii178-ii178

Author(s):

Neal Prakash ◽

Rachel Tran ◽

Elizabeth Strain

Keyword(s):

Quality Of Life ◽

Peripheral Neuropathy ◽

Lower Extremity ◽

Rating Scale ◽

Numerical Rating Scale ◽

Post Treatment ◽

Therapeutic Modality ◽

Convenience Sample ◽

Scrambler Therapy

Abstract BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious consequence of cancer treatment that, for up to 30% of patients, persists beyond six months of completing chemotherapy. Scrambler therapy (ST) is a therapeutic modality with emerging evidence supporting its ability to diminish CIPN symptoms. METHODS Data was from a convenience sample of 24 CIPN patients (with symptoms between 1-240 months after platinum-based, taxane, or combination chemotherapy) completing 10 sessions of ST using the Calmare® device in the City of Hope Outpatient Physical Therapy Department. Patients were treated for ~45 minutes per session over 10 sessions. Patients received a standardized assessment pre- and post ST that included: EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20), mono-filament testing, pain intensity numerical rating scale, numbness scale, extensor hallicus longus strength, Timed Up and Go, Romberg, and single leg balance. RESULTS Regardless of length of symptoms, significant changes were seen in post-treatment assessment of quality of life as measured by the QLQ-CIPN-20 and numbness scale. Post-treatment QLQ-CIPN-20 total scores decreased by an average of 7.1 points (n= 24, p< .01). Numbness in the left lower extremity decreased by an average of 1 point of the 0-4 point scale (n=24, p=.0007) and 1.09 points on the right lower extremity (n=24, p < .0004). There was a trend towards improvements in pain, monofilament testing, single leg balance, and Romberg test, though they did not reach a level of significance. Surprisingly, only 3 of 24 patients reported pain related to their CIPN at the start of treatment. CONCLUSION For patients with CIPN, scrambler therapy improves numbness and improves quality of life measures. This suggests an important role for this treatment modality in cancer patients suffering from this debilitating condition.

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A Case of Catatonia in a 14-Year-Old Girl with Schizophrenia Treated with Electroconvulsive Therapy

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie ◽

10.1024/1422-4917/a000211 ◽

2013 ◽

Vol 41 (1) ◽

pp. 69-74 ◽

Cited By ~ 10

Author(s):

Frank Häßler ◽

Olaf Reis ◽

Steffen Weirich ◽

Jacqueline Höppner ◽

Birgit Pohl ◽

...

Keyword(s):

Case Report ◽

Treatment Response ◽

Electroconvulsive Therapy ◽

Rating Scale ◽

Combined Treatment ◽

Adolescent Patient

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

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Effectiveness of a digital therapeutic as adjunct to treatment with medication in pediatric ADHD

npj Digital Medicine ◽

10.1038/s41746-021-00429-0 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Scott H. Kollins ◽

Ann Childress ◽

Andrew C. Heusser ◽

Jacqueline Lutz

Keyword(s):

Video Game ◽

Primary Outcome ◽

Rating Scale ◽

Stimulant Medication ◽

Additional Treatment ◽

Adhd Medication ◽

Open Label ◽

Serious Adverse Events ◽

Treatment Benefit ◽

Hyperactivity Disorder

AbstractSTARS-Adjunct was a multicenter, open-label effectiveness study of AKL-T01, an app and video-game-based treatment for inattention, as an adjunct to pharmacotherapy in 8–14-year-old children with attention-deficit/hyperactivity disorder (ADHD) on stimulant medication (n = 130) or not on any ADHD medication (n = 76). Children used AKL-T01 for 4 weeks, followed by a 4-week pause and another 4-week treatment. The primary outcome was change in ADHD-related impairment (Impairment Rating Scale (IRS)) after 4 weeks. Secondary outcomes included changes in IRS, ADHD Rating Scale (ADHD-RS). and Clinical Global Impressions Scale—Improvement (CGI-I) on days 28, 56, and 84. IRS significantly improved in both cohorts (On Stimulants: −0.7, p < 0.001; No Stimulants: −0.5, p < 0.001) after 4 weeks. IRS, ADHD-RS, and CGI-I remained stable during the pause and improved with a second treatment period. The treatment was well-tolerated with no serious adverse events. STARS-Adjunct extends AKL-T01’s body of evidence to a medication-treated pediatric ADHD population, and suggests additional treatment benefit.

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361 Relative Effectiveness of Cognitive Behavioral Therapy and its Components in Improving Insomnia Symptoms in Older Adults

SLEEP ◽

10.1093/sleep/zsab072.360 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A144-A144

Author(s):

Kathleen O’Hora ◽

Beatriz Hernandez ◽

Laura Lazzeroni ◽

Jamie Zeitzer ◽

Leah Friedman ◽

...

Keyword(s):

Older Adults ◽

Cognitive Behavioral Therapy ◽

Behavioral Therapy ◽

Sleep Onset ◽

Post Treatment ◽

Cognitive Behavioral ◽

Sleep Onset Latency ◽

Significant Group ◽

Time Interaction ◽

Insomnia Symptoms

Abstract Introduction The prevalence of insomnia complaints in older adults is 30–48%, compared to 10–15% in the general population. Cognitive Behavioral Therapy for Insomnia (CBT-I) is a first-line, non-pharmacological sleep treatment for Insomnia. However, the relative impact of Behavioral (BT) and Cognitive (CT) components compared to that of CBT-I in older adults is unknown. Methods 128 older adults with insomnia were randomized to receive CBT-I, BT, or CT. Sleep diaries and the Insomnia Severity Index (ISI) were collected pre- and post-treatment and at a 6-month follow-up. We conducted split-plot linear mixed models with age and sex as covariates to assess within and between subject changes to test effects of group, time, and their interaction on ISI, sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), time in bed (TIB), sleep efficiency (SE), and percent of treatment responders (ISI decrease>7) and remitters (ISI<8). Effect size (d) was calculated by dividing the difference between means by the root-mean-squared error of the mixed effects model. Results All treatments lead to a significant improvement across outcome measures at post-treatment (p’s<0.001) and 6-months (p’s<0.01), with the exception of TIB, response, and remission. For TIB, there was a significant Group x Time interaction (p<0.001): while all treatments significantly reduced TIB post-treatment relative to baseline, CBT-I (p<0.001,d=-2.26) and BT (p<0.001,d=-1.59) performed significantly better than CT (p=0.003, d=-0.68). In contrast, at 6-months CBT-I (p<0.001,d=-1.16) performed significantly better at reducing TIB than CT (p=0.195,d=-0.24) or BT (p=0.023,d=-0.61) relative to baseline. There was also a non-significant trend for a Group x Time interaction for remission status (p=0.062). Whereas, the percentage of remitters within all groups post-treatment did not differ from chance (p>0.234), at 6 months, the percentage of remitters was significantly higher than chance in CBT-I (73.63%,p=0.026) and BT (78.08%,p=0.012), but not CT (47.85%,p=0.826). There were no other significant time or interaction effects (all p>0.05). Conclusion CBT-I and its components are effective in improving subjective insomnia symptoms in older adults. Evidence suggests CBT-I may be superior to either CT or BT alone in improving TIB in older adults. Support (if any) NIMHR01MH101468; MIRECC at VAPAHCS

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Differential response to scrambler therapy by neuropathic pain phenotypes

Scientific Reports ◽

10.1038/s41598-021-89667-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Young Gi Min ◽

Hyun Seok Baek ◽

Kyoung-Min Lee ◽

Yoon-Ho Hong

Keyword(s):

Neuropathic Pain ◽

Treatment Outcome ◽

Rating Scale ◽

Numerical Rating Scale ◽

Brief Pain Inventory ◽

Differential Response ◽

Open Label ◽

Numerical Rating ◽

Scrambler Therapy ◽

Post Hoc

AbstractScrambler therapy is a noninvasive electroanalgesia technique designed to remodulate the pain system. Despite growing evidence of its efficacy in patients with neuropathic pain, little is known about the clinical factors associated with treatment outcome. We conducted a prospective, open-label, single-arm trial to assess the efficacy and safety of scrambler therapy in patients with chronic neuropathic pain of various etiologies. A post-hoc analysis was performed to investigate whether cluster analysis of the Neuropathic Pain Symptom Inventory (NPSI) profiles could identify a subgroup of patients regarding neuropathic pain phenotype and treatment outcome. Scrambler therapy resulted in a significant decrease in the pain numerical rating scale (NRS) score over 2 weeks of treatment (least squares mean of percentage change from baseline, − 15%; 95% CI − 28% to − 2.4%; p < 0.001). The mean score of Brief Pain Inventory (BPI) interference subdimension was also significantly improved (p = 0.022), while the BPI pain composite score was not. Hierarchical clustering based on the NPSI profiles partitioned the patients into 3 clusters with distinct neuropathic pain phenotypes. Linear mixed-effects model analyses revealed differential response to scrambler therapy across clusters (p = 0.003, pain NRS; p = 0.072, BPI interference subdimension). Treatment response to scrambler therapy appears different depending on the neuropathic pain phenotypes, with more favorable outcomes in patients with preferentially paroxysmal pain rather than persistent pain. Further studies are warranted to confirm that capturing neuropathic pain phenotypes can optimize the use of scrambler therapy.

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LI-RADS treatment response algorithm after first-line DEB-TACE: reproducibility and prognostic value at initial post-treatment CT/MRI

Abdominal Radiology ◽

10.1007/s00261-021-03043-6 ◽

2021 ◽

Author(s):

Ali Pirasteh ◽

E. Aleks Sorra ◽

Hector Marquez ◽

Robert C. Sibley ◽

Julia R. Fielding ◽

...

Keyword(s):

Treatment Response ◽

Prognostic Value ◽

Post Treatment ◽

First Line

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Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington’s Disease: Results From the ARC-HD Open-label Study

CNS Spectrums ◽

10.1017/s1092852920002655 ◽

2021 ◽

Vol 26 (2) ◽

pp. 164-165

Author(s):

Samuel Frank ◽

Claudia M. Testa ◽

David Stamler ◽

Elise Kayson ◽

David Oakes ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Rating Scale ◽

Study Drug ◽

Motor Dysfunction ◽

Open Label ◽

Entire Treatment Period ◽

End Of Treatment ◽

Pharmaceutical Industries

AbstractBackgroundChorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.MethodsPatients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.ResultsOf 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.ConclusionsThe type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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StopWatch: Pilot study for an Apple Watch application for youth with ADHD

Digital Health ◽

10.1177/20552076211001215 ◽

2021 ◽

Vol 7 ◽

pp. 205520762110012

Author(s):

John E Leikauf ◽

Carlos Correa ◽

Andrew N Bueno ◽

Vicente Peris Sempere ◽

Leanne M Williams

Keyword(s):

Pilot Study ◽

Mixed Models ◽

Rating Scales ◽

Haptic Feedback ◽

Rating Scale ◽

Open Label ◽

Software Application ◽

Hyperactivity Disorder ◽

Further Development ◽

Youth With Adhd

Introduction To address the need for non-pharmacologic, scalable approaches for managing attention-deficit and hyperactivity disorder (ADHD) in young people, we report the results of a study of an application developed for a wearable device (Apple Watch) that was designed to track movement and provide visual and haptic feedback for ADHD. Methods Six-week, open label pilot study with structured rating scales ADHD and semi-structured qualitative interview. Apple Watch software application given to users that uses actigraphy and graphic interface as well as haptic feedback to provide feedback to users about level of movement during periods of intentional focus. Linear mixed models to estimate trajectories. Results Thirty-two participants entered the study. This application was associated with improvement in ADHD symptoms over the 6 weeks of the study. We observed an ADHD-Rating Scale change of β = −1.2 units/week (95% CI = −0.56 to −1.88, F = 13.4, P = .0004). Conclusions These positive clinical outcomes highlight the promise of such wearable applications for ADHD and the need to pursue their further development.

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