Effects of a Brief Mindful Hypnosis Intervention on Stress Reactivity: A Randomized Active Control Study.

A novel, audio-based brief mindful hypnosis (BMH) intervention for reducing stress-reactivity during the Trier Social Stress Test (TSST) was investigated. Fifty-five college-aged participants with elevated stress were randomized to BMH or a cognitive training (CT) active-control condition. Participants received a BMH or CT session and downloaded the audio-recorded intervention for daily home practice. Approximately 1 week later, participants received their second BMH or CT session and then completed the TSST. Results indicated BMH produced significant and medium effects in reducing stress reactivity and weekly stress and increasing mindfulness, with large increases in immediate relaxation compared to the CT active control. BMH demonstrated excellent adherence and was rated highly regarding satisfaction, ease of practice, perceived benefit, and likelihood of future use. This study provides the first empirical support that BMH is superior to an active-control intervention for reducing stress reactivity while significantly increasing mindfulness and relaxation.

Test-Retest Reliability of the Stanford Hypnotic Susceptibility Scale, Form C and the Elkins Hypnotizability Scale.

This project aimed to assess the consistency of hypnotizability over repeated assessments when measured by the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C), and the Elkins Hypnotizability Scale (EHS) and to contrast score distribution and pleasantness of these scales. University students were administered either the SHSS:C or the EHS twice with a one-week delay by separate experimenters. Test-retest reliability of the EHS and the SHSS:C was r s =.82 (.71-.92) and r s =.66, 95% (.47-.86), respectively (Spearman's correlation). Hypnotizability was comparable at test and retest in the EHS group, SHSS:C scores decreased by the retest. We found that the SHSS:C produced higher scores than the EHS, and the pleasantness of the 2 scales was comparable. Overall, our results supported the reliability of the EHS, while SHSS:C scores were more inconsistent between the 2 assessments. More research is warranted.

Are 24-hour motor activity patterns associated with continued rapid response to ketamine?

PURPOSE: This study examined the links between 24-hour activity patterns (specifically, amplitude and timing of wrist activity) and the persisting qualities of clinical antidepressant response to the glutamatergic modulator ketamine. METHODS: Twenty-four-hour activity patterns were compared across 5 days of 24-hour activity rhythms in patients with major depressive disorder who displayed either a brief antidepressant response (24-48 hours), a continued antidepressant response (>72 hours), or no antidepressant response to ketamine. These postinfusion-response profiles were then used retrospectively to examine cohort-specific fitted parameters at baseline, postinfusion day 1 (D1), and postinfusion D3. RESULTS: Relative to the nonresponders, the cohort experiencing a brief antidepressant response had blunted 24-hour amplitude that extended from baseline through D3 and postketamine phase advance of activity on D1 that reverted to baseline on D3. Relative to the nonresponders, the cohort experiencing a continued antidepressant response to ketamine had phase-advanced activity at both baseline and D1, as well as increased amplitude on D1 and D3. CONCLUSION: Taken together, the results suggest that the time course of antidepressant response to ketamine is influenced by underlying biological differences in motor activity timekeeping. These differences may provide clues that link durable mood response with the molecular machinery of the circadian system, thus leading to more effective interventions. In addition, biomarkers of preinfusion motor activity (eg, amplitude, timing) may be useful for recommending future individualized treatment interventions, to the extent that they help identify patients who may relapse quickly after treatment.

An assessment of the anti-fatigue effects of ketamine from a double-blind, placebo-controlled, crossover study in bipolar disorder.

BACKGROUND: Fatigue is a multidimensional condition that is difficult to treat with standard monoaminergic antidepressants. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist produces rapid and robust improvements in depressive symptoms in treatment-resistant depression. However, there is a dearth of literature examining the anti-fatigue effects of ketamine. We hypothesize that ketamine will rapidly improve fatigue symptoms in treatment-resistant depressed patients. METHODS: This is an exploratory analysis of data obtained from two double-blind, randomized, placebo-controlled, crossover trials. A total of 36 participants with treatment-resistant bipolar I or II disorder in a depressive episode (maintained on therapeutic levels of lithium or valproate) received a single infusion of ketamine hydrochloride intravenously (0.5 mg/kg over 40 min) or placebo. A post-hoc analysis compared fatigue scores on ketamine vs. placebo at 10 time points from baseline through 14 days post-treatment using the National Institute of Health-Brief Fatigue Inventory. RESULTS: A linear mixed model showed that ketamine significantly lowered fatigue scores compared to placebo from 40 min post-treatment to Day 14 with the exception of Day 7. The largest difference in anti-fatigue effects between placebo and ketamine was at day 2 (d=0.58, p<0.05). The effect remained significant after controlling for changes in non-fatigue depressive symptoms. LIMITATION: The retrospective nature and a small sample size are study limitations. CONCLUSIONS: Ketamine rapidly improved fatigue relative to placebo in a group of individuals with treatment-resistant bipolar depression. NMDAR is a glutamate receptor; hence, glutamate may represent a valuable target to study the clinical efficacy of new anti-fatigue approaches in multiple disorders.

Development of a clinician-administered National Institutes of Health-Brief Fatigue Inventory: A measure of fatigue in the context of depressive disorders.

OBJECTIVE: Fatigue is a complex, multidimensional condition. Although it is often associated with depression, it is not known whether it has a distinct network from depression or whether it can be clinically evaluated, separately. This study describes preliminary findings in the development of a brief, clinician-administered instrument to measure fatigue in the context of depressive disorders using items from existing clinician-administered depression and mania scales. METHODS: Based on items from prior fatigue measurements, items were selected from the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale, and Structured Interview Guide for HDRS with Atypical Depression. The final items composed the NIH-Brief Fatigue Inventory (NIH-BFI). Responses from 89 depressed adults collected pre- and post-antidepressant therapy (ADT) determined the reliability and consistency of the NIH-BFI using Cronbach's alpha and principal components analysis (PCA). Correlations of the NIH-BFI and fatigue items from other scales before and after ADT explored validity. RESULTS: The 7-item NIH-BFI had Cronbach alphas ranging from 0.81 to 0.88 and PCA indicating a single dimension. The NIH-BFI score was strongly correlated (r = 0.73, p < 0.001) with fatigue items from Beck Depression Index, with MADRS without fatigue items (r = 0.77, p < 0.001), and HDRS without fatigue items (pre: r = 0.69, p < 0.001). CONCLUSIONS: Preliminary findings show support for internal consistency reliability and validity of the NIH-BFI, a clinician-administered measure of fatigue. Further testing in other clinical populations is recommended to obtain additional information on reliability and validity. The NIH-BFI provides a method for clinician-rated fatigue that may be a separate from depression.

Effect of baseline anxious depression on initial and sustained antidepressant response to ketamine.

OBJECTIVE: Patients with anxious depression are typically more difficult to treat with monoaminergic antidepressants compared to those with nonanxious depression. Although novel research has shown that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapidly acting, relatively sustained effects in treating depression, we predicted that, consistent with the existent literature on traditional antidepressants, patients with anxious depression would have a poorer antidepressant response. METHOD: Twenty-six inpatients with treatment-resistant major depressive disorder (MDD) (DSM-IV criteria) received a single infusion of ketamine (0.5 mg/kg over 40 minutes) from January 2006-March 2013 and were followed for 28 days. A post hoc analysis compared treatment response and relapse using the Montgomery-Asberg Depression Rating Scale (MADRS) in patients with anxious versus nonanxious depression. Anxious depression was defined as MDD plus a Hamilton Depression Rating Scale anxiety/somatization factor score ≥ 7. RESULTS: Both anxious and nonanxious depressed patients responded positively to ketamine. A linear mixed model controlling for baseline with the MADRS revealed a significant group main effect (P = .03) and group-by-time interaction (P = .01). Post hoc tests indicated that patients with anxious depression had significantly fewer depression symptoms compared to those with nonanxious depression at days 1 through 5, 9 through 12, 15 through 17, and 25, with no significant group differences in dissociative (P = .62) or psychotic (P = .41) side effects. Regarding responders, patients with anxious depression relapsed significantly later than those with nonanxious depression (median ± SE = 19.0 ± 17.9 vs 1.0 ± 0.0 days to relapse, respectively; χ² = 9.30; P = .002). CONCLUSIONS: Unexpectedly, patients with anxious depression responded better to ketamine than those with nonanxious depression, with longer time to relapse and no side effect differences. This finding gives promise for the role of novel glutamatergic medications for the treatment of those with anxious depression, a traditionally difficult-to-treat subgroup of depressed patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00088699.

Increased fear-potentiated startle in major depressive disorder patients with lifetime history of suicide attempt.

BACKGROUND: Suicide is a common reason for psychiatric emergency and morbidity, with few effective treatments. Anxiety symptoms have emerged as potential modifiable risk factors in the time before a suicide attempt, but few studies have been conducted using laboratory measures of fear and anxiety. We operationally defined fear and anxiety as increased startle reactivity during anticipation of predictable (fear-potentiated startle) and unpredictable (anxiety-potentiated startle) shock. We hypothesized that a lifetime history of suicide attempt (as compared to history of no suicide attempt) would be associated with increased fear-potentiated startle. METHODS: A post-hoc analysis of fear- and anxiety-potentiated startle was conducted in 28 medication-free patients with Major Depressive Disorder (MDD) divided according to suicide attempt history. RESULTS: The magnitude of fear-potentiated startle was increased in depressed patients with lifetime suicide attempts compared to those without a lifetime history of suicide attempt (F(1,26)=5.629, p=.025). There was no difference in anxiety-potentiated startle by suicide attempt history. LIMITATIONS: This is a post-hoc analysis of previously analyzed patient data from a study of depressed inpatients. Further replication of the finding with a larger patient sample is indicated. CONCLUSIONS: Increased fear-potentiated startle in suicide attempters suggests the role of amygdala in depressed patients with a suicide attempt history. Findings highlight the importance of anxiety symptoms in the treatment of patients at increased suicide risk.