Kathryn M. Connor

Spirituality, Resilience, and Anger in Survivors of Violent Trauma: A Community Survey

This study evaluates the relationship between spirituality, resilience, anger and health status, and posttraumatic symptom severity in trauma survivors. A community sample (N = 1,200) completed an online survey that included measures of resilience, spirituality (general beliefs and reincarnation), anger, forgiveness, and hatred. In survivors of violent trauma (n = 648), these measures were evaluated with respect to their relationship to physical and mental health, trauma-related distress, and posttraumatic symptom severity. Using multivariate regression models, general spiritual beliefs and anger emerged in association with each outcome, whereas resilience was associated with health status and posttraumatic symptom severity only. Forgiveness, hatred, and beliefs in reincarnation were not associated with outcome. The importance of these findings to treating trauma survivors is discussed.

A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder

BACKGROUND The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD. METHODS Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated. RESULTS Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated. CONCLUSIONS Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials.

Randomized, controlled trial of telcagepant for the acute treatment of migraine

Background: The neuropeptide calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology. In this large phase 3 clinical trial, we sought to confirm the efficacy of telcagepant, the first orally bioavailable CGRP receptor antagonist. Methods: Adults with migraine with or without aura (International Headache Society criteria) treated a moderate or severe attack with oral telcagepant 50 mg (n = 177), 150 mg (n = 381), 300 mg (n = 371), or placebo (n = 365) in a randomized, double-blind trial. The 5 co-primary endpoints were pain freedom, pain relief, and absence of photophobia, absence of phonophobia, and absence of nausea, all at 2 hours postdose. The key secondary endpoint was 2–24 hour sustained pain freedom. The prespecified primary efficacy analyses evaluated the 150 mg and 300 mg groups; the 50-mg group was included on an exploratory basis to further characterize the dose response but was not prespecified for analysis. Tolerability was assessed by adverse experience reports. Results: Telcagepant 300 mg was more effective (p ≤ 0.001) than placebo on all primary endpoints and the key secondary endpoint, as was telcagepant 150 mg (p ≤ 0.05). Telcagepant 300 mg showed a slight numeric advantage over telcagepant 150 mg on most measures. Telcagepant 50 mg values were numerically intermediate between placebo and telcagepant 150 mg and 300 mg. The percentages of patients with adverse experiences were 32.2% for telcagepant 50 mg, 32.0% for telcagepant 150 mg, 36.2% for telcagepant 300 mg, and 32.2% for placebo. Conclusions: This study confirmed previous findings that telcagepant 300 mg was effective at relieving pain and other migraine symptoms at 2 hours and providing sustained pain freedom up to 24 hours. In this study, telcagepant 150 mg was also effective. Telcagepant was generally well tolerated.

An abbreviated version of the Connor-Davidson Resilience Scale (CD-RISC), the CD-RISC2: psychometric properties and applications in psychopharmacological trials.

Resilience may be an important component of the prevention of neuropsychiatric disease. Resilience has proved to be quantifiable by scales such as the Connor-Davidson Resilience Scale (CD-RISC). Here, we introduce a two-item version of this scale, the CD-RISC2. We hypothesize that this shortened version of the scale has internal consistency, test-retest reliability, convergent validity, and divergent validity as well as significant correlation with the full scale. Additionally, we hypothesize that the CD-RISC2 can be used to assess pharmacological modification of resilience. We test these hypotheses by utilizing data from treatment trials of post-traumatic stress disorder, major depression, and generalized anxiety disorder with setraline, mirtazapine, fluoxetine, paroxetine, venlafaxine XR, and kava as well as data from the general population, psychiatric outpatients, and family medicine clinic patients.

Trauma, resilience and saliostasis: effects of treatment in post-traumatic stress disorder.

There has been growing interest in the concept of resilience and the question as to whether psychotropic medications or psychosocial treatments might have resilience-enhancing effects. This pilot study investigates resilience in a sample of patients with post-traumatic stress disorder (PTSD) before and after treatment. Effects of treatment with tiagabine, fluoxetine, sertraline alone, and sertraline with cognitive behavioural therapy on resilience were assessed using the Connor-Davidson Resilience Scale (CD-RISC). Changes in resilience after treatment were measured and response to treatment was predicted from demographic, resilience and baseline disability measures. Changes in resilience following treatment were statistically significant. Items that showed the greatest change related to confidence, control, coping, knowing where to turn for help and adaptability. Items showing the least change related to religious and existential aspects of resiliency, effort, acting on a hunch, decision-making and goals. In linear and logistic regression models, gender, baseline CD-RISC score, baseline Sheehan Disability Scale score and an individual item from the CD-RISC scale, ‘Sense of Humor’, were significant predictors of response to treatment. Treatment of PTSD significantly improved resilience and reduced symptoms in this sample. Further controlled studies are indicated.

Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial

BACKGROUND Based on an earlier pilot study, as well as a theoretical consideration of its mechanism of action, we undertook a placebo-controlled, double-blind trial of mirtazapine in posttraumatic stress disorder. METHODS Twenty-nine patients were randomized to receive drug up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26. Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview (SPRINT) Global Improvement item and total score. Secondary measures comprised the Davidson Trauma Scale, Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale. Adverse events were also measured. RESULTS On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure, rates of response were 64.7% and 20.0% for mirtazapine and placebo. Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global, Structured Interview for Posttraumatic Stress Disorder, and Hospital Anxiety Depression Scale anxiety subscale scores. The drug was well tolerated. CONCLUSIONS Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms.

Olanzapine in the treatment of post-traumatic stress disorder: a pilot study

Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2: 1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapines not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients.

Posttraumatic distress and coping strategies among rescue workers after an earthquake.

Abstract Disaster workers are at high risk for developing psychiatric morbidity. This study examined the prevalence rates of psychiatric and posttraumatic distress and the relationship between psychiatric and posttraumatic morbidity and coping strategies among rescue workers following an earthquake in Taiwan on September 21, 1999. Eighty‐four male firefighters who had been exposed to earthquake rescue work were assessed 5 months after the event. The Chinese Health Questionnaire (CHQ), the Impact of Event Scale (IES), and the Ways of Coping Questionnaire (WCQ) were used to assess psychiatric morbidity, posttraumatic morbidity, and coping strategies. The observed prevalence rates were 16.7% and 21.4% for general psychiatric morbidity and posttraumatic morbidity, respectively. Results from multivariate logistic regression indicated that job experience and confrontive coping were significant predictors of psychiatric morbidity, while job experience, distancing, escape‐avoidance, and positive reappraisal were significant predictors of posttraumatic morbidity. Rescue workers with longer job experience were at the highest risk for developing psychiatric and posttraumatic distress.

Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention

Objective: To evaluate whether the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant might be effective for migraine prevention. Methods: In this randomized, double-blind, placebo-controlled, multicenter trial (ClinicalTrials.gov NCT00797667), patients experiencing 3–14 migraine days during a 4-week baseline were randomized to telcagepant 140 mg, telcagepant 280 mg, or placebo twice daily for 12 weeks. Efficacy was assessed by mean monthly headache days and migraine/probable migraine days (headache plus ≥1 associated symptom). Results: The trial was terminated following a recommendation from the Safety Monitoring Board due to hepatotoxicity concerns. At termination, the planned 660 patients had been randomized, 656 had been treated with ≥1 dose of study medication, and 14 had completed the trial. The mean treatment duration was 48–50 days. Thirteen patients, all in the telcagepant groups, had an alanine aminotransferase (ALT) elevation ≥3× the upper limit of normal and 7 of these also had an aspartate aminotransferase elevation ≥3× the upper limit of normal. Two patients had very high symptomatic transaminase elevations that occurred within 2–6 weeks of treatment initiation and resolved after treatment discontinuation. The originally planned efficacy analysis over 12 weeks was not performed due to limited data at later time points, but there was evidence that telcagepant resulted in a larger reduction from baseline than placebo for mean monthly headache days (month 1: 140 mg = −2.9, 280 mg = −3.1, placebo = −1.7; p < 0.05) and migraine/probable migraine days (month 1: 140 mg = −2.7, 280 mg = −3.0, placebo = −1.6; p < 0.05). Conclusions: These data suggest a potential role for CGRP receptor antagonism in migraine prophylaxis. However, the observed aminotransferase elevations do not support the use of telcagepant for daily administration. Classification of evidence: This study provides Class II evidence that in patients with migraine, telcagepant taken daily reduces headache days by 1.4 days per month compared to placebo and causes 2.5% of patients to have elevations of serum ALT levels.

Efficacy of olanzapine in social anxiety disorder: a pilot study

Based on evidence suggesting anxiolytic properties of the atypical antipsychotic olanzapine, this study was conducted to evaluate whether olanzapine may be efficacious in treating social anxiety disorder (SAD). This study was an 8-week, double-blind, placebo-controlled evaluation of olanzapine as monotherapy in which 12 patients with the DSM-IV diagnosis of SAD were randomized to either olanzapine (n= 7) or placebo (n= 5). An initial dose of 5 mg/day was titrated to a maximum of 20 mg/day. Baseline to endpoint scores from the Brief Social Phobia Scale (BSPS), Social Phobia Inventory (SPIN), Liebowitz Social Anxiety Scale and Sheehan Disability Scale, as well as Clinical Global Impression-Improvement ratings, were compared for olanzapine versus placebo. Seven subjects completed all 8 weeks of the study, four in the olanzapine group and three in the placebo group. In the intent-to-treat analysis, olanzapine yielded greater improvement than placebo on the primary measures: BSPS (p= 0.02) and SPIN (p= 0.01). Both treatments were well tolerated, although the olanzapine group had more drowsiness and dry mouth. Olanzapine and placebo were both associated with negligible weight gain. Olanzapine was superior to placebo on the primary outcome measures in this preliminary study of SAD. Additional studies of olanzapine as a treatment for SAD are warranted.