Treatment-resistant Posttraumatic Stress Disorder Research Articles

The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study

Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model

Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by a life-threatening event causing intense fear. Recently, functional neuroimaging studies have suggested that amygdala hyperactivity is responsible for the symptoms of PTSD. Deep brain stimulation (DBS) can functionally reduce the activity of a cerebral target by delivering an electrical signal through an electrode. We tested whether DBS of the amygdala could be used to treat PTSD symptoms. Rats traumatized by inescapable shocks, in the presence of an unfamiliar object, develop the tendency to bury the object when re-exposed to it several days later. This behavior mimics the symptoms of PTSD. 10 Sprague–Dawley rats underwent the placement of an electrode in the right basolateral nucleus of the amygdala (BLn). The rats were then subjected to a session of inescapable shocks while being exposed to a conspicuous object (a ball). Five rats received DBS treatment while the other 5 rats did not. After 7 days of treatment, the rats were re-exposed to the ball and the time spent burying it under the bedding was recorded. Rats treated with BLn DBS spent on average 13 times less time burying the ball than the sham control rats. The treated rats also spent 18 times more time exploring the ball than the sham control rats. In conclusion, the behavior of treated rats in this PTSD model was nearly normalized. We argue that these results have direct implications for patients suffering from treatment-resistant PTSD by offering a new therapeutic strategy.

Cortisol metabolic predictors of response to psychotherapy for symptoms of PTSD in survivors of the World Trade Center attacks on September 11, 2001

A proportion of subjects with symptoms of posttraumatic stress disorder (PTSD) are unresponsive to specialized psychotherapy, but a biological basis for this has not been described. To observe whether differences in cortisol or its metabolites predict or correlate with response to therapy for PTSD symptoms, cortisol and its metabolites were measured from urine samples at pre-treatment, at the conclusion of psychotherapy, and at 3-month follow-up. 28 survivors of the World Trade Center attacks on September 11, 2001 seeking psychological treatment for PTSD symptoms received four sessions of either exposure therapy or supportive counseling, followed by up to 10 sessions of prolonged exposure in a specialized PTSD treatment program at a private hospital serving the New York City metropolitan area. 24-h mean integrated cortisol excretion was assessed by radioimmunoassay (RIA); urinary free cortisol and metabolites cortisone, 5alpha-tetrahydrocortisol (5alpha-THF), 5beta-tetrahydrocortisol, and tetrahydrocortisone were assessed by gas chromatography-mass spectrometry (GC-MS); and indices of enzyme activity for 5alpha- and 5beta-reductase and for the 11beta-hydroxysteroid dehydrogenases were derived from the metabolite and glucocorticoid measures. 5alpha-Reductase activity was significantly lower at pre-treatment among non-responders, whereas there were no significant pre-treatment differences between responders and non-responders in any other hormone or metabolite level. In repeated measures analyses across the three time points, 5alpha-reductase activity, as well as 5alpha-THF and total glucocorticoids, significantly differed between responders and non-responders. For urinary cortisol measured by RIA, there was a significant groupxtime interaction indicating that, although not different at pre-treatment, urinary cortisol levels declined over time in the non-responder group, such that by follow-up, lowered cortisol significantly distinguished non-responders from responders. Indices of 5alpha-reductase activity, including 5alpha-THF and total glucocorticoids, were significantly negatively correlated with avoidance symptom severity at pre-treatment. At follow-up, indices of 5alpha-reductase activity were significantly negatively correlated with severity of all three PTSD symptom clusters and with total PTSD severity scores. Lower 5alpha-reductase activity is associated with avoidance severity and predicts non-responsiveness to psychological treatment for PTSD symptomatology. Relatively diminished 5alpha-reductase activity may mark a state of primary vulnerability, perhaps via attenuated peripheral catabolism of cortisol resulting in the suppression of hypothalamic-pituitary-adrenal axis responsiveness. Lower cortisol levels appear later in the progression to chronic, treatment-resistant PTSD.

Post Traumatic Stress Disorder—The Neurofeedback Remedy

Abstract The application of neurofeedback to post traumatic stress disorder (PTSD) in returning veterans is described herein and is illustrated with two case histories. Initially, frequency-based electroencephalogram training was employed to promote functional recovery, in the manner of the traditional sensorimotor rhythm/beta approach. An optimization procedure was employed in which the reinforcement frequency is tailored to the client on the basis of symptom response, with particular regard for the regulation of arousal. Low frequencies, down to .01 Hz, have been found especially useful in the remediation of post-traumatic stress disorder. This training was complemented with traditional alpha-theta work as pioneered at the Menninger Foundation and by Peniston. The objective here is experiential, because prior traumas typically are revisited in a nonforced, nontraumatic manner. The benign witnessing of traumas consolidates the experience of safety for which the prior training laid the groundwork. Collectively, this approach has been found to be much better tolerated than traditional exposure therapies. In addition, it is helpful in the shedding of substance dependencies that are common in treatment-resistant PTSD

Brief Cognition-Focused Group Therapy for Depressive Symptoms in Chronic Posttraumatic Stress Disorder: A Pilot Study

ABSTRACT A growing literature supports the inclusion of cognitive therapy components in the treatment of posttraumatic stress disorder (PTSD) and, in many cases, concomitant depression. However, further research is needed to examine whether cognitive therapies may serve as an effective approach to emotional regulation in cases of chronic treatment-resistant PTSD (e.g., combat veterans who have been in treatment for 20 or more years). This article outlines a brief outpatient cognitive emotion-management group with a present focus. The intervention, based on cognitive appraisal theory, is designed to reduce negative cognitive appraisals and depressive symptoms among individuals with treatment-resistant PTSD. Participants were 21 men and women (4 male cohorts and 1 female cohort) in a VA treatment program for trauma-related distress who met screening criteria for high depressive symptoms and evidenced maladaptive cognitive appraisals of stress. For 14 participants with complete data, the treatment yielded pa...

Chronic PTSD Treated With Metacognitive Therapy: An Open Trial

This paper reports on an open trial of metacognitive therapy (MCT) for chronic PTSD. MCT does not require imaginal reliving, prolonged exposure, or challenging of thoughts about trauma. It is based on an information-processing model of factors that impede normal and in-built recovery processes. It is targeted at modifying maladaptive styles of worry/rumination and attention so that emotional processing can proceed spontaneously. Eleven out of 13 patients with a mean duration of PTSD of 19.5 months completed treatment. Therapists followed the treatment manual by Wells and Sembi (2004b). Self-report measures of PTSD symptoms, anxiety and depression, and assessor ratings of PTSD were administered at pre- and posttreatment, and at 3- and 6-month follow-up. Treatment appeared to result in large and significant improvements on all measures of PTSD and general measures of anxiety and depression. Statistically significant treatment gains were maintained at 3- and 6-month follow-up. Jacobson's criteria for recovery showed that 90% of patients were recovered at posttreatment. At 6-month follow-up approximately 89% were recovered or reliably improved. Results suggest that MCT could be highly effective and extend evidence of its applicability to more treatment-resistant chronic PTSD cases. Comparisons against other active interventions are now clearly indicated.

Creatine monohydrate supplementation may improve symptoms of treatment-resistant post-traumatic stress disorder

Creatine monohydrate supplementation may improve symptoms of treatment-resistant post-traumatic stress disorder

Open Study of Creatine Monohydrate in Treatment-Resistant Posttraumatic Stress Disorder

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.Sir: Creatine-containing compounds play an important role in brain energy homeostasis and may have a beneficial effect on brain functioning.1-3 Accumulated evidence suggests the possible involvement of altered cerebral energy metabolism in the pathophysiology of posttraumatic stress disorder (PTSD).4 Oral creatine supplementation may increase brain creatine level and modify brain high-energy phosphate metabolism in hypoactive brain areas in subjects with treatment-resistant PTSD.†‹

Quetiapine treatment in an open trial in combat-related post-traumatic stress disorder with psychotic features

Patients with combat-related post-traumatic stress disorder (PTSD) with psychotic features frequently fail to respond to antidepressants. Previous research has shown that these patients improve significantly after monotherapy with two atypical antipsychotics, olanzapine and risperidone. This study investigated the clinical outcome of another atypical antipsychotic, quetiapine, in war veterans with combat-related PTSD with psychotic features. Male war veterans (n=53) with DSM-IV-diagnosed PTSD with psychotic symptoms completed 8 wk of in-patient treatment with quetiapine (25-400 mg/d). The reductions in the total and subscale scores on the Clinician-Administered PTSD Scale (CAPS), and the increase in the Clinical Global Impression - Improvement Scale (CGI-I) were the primary outcome measures, and reductions in the Positive and Negative Syndrome Scale (PANSS) were the secondary outcome measures. The CGI - Severity of Illness scale (CGI-S) was used to assess the global clinical improvement. Drug-Induced Extrapyramidal Symptoms scale recorded adverse effects. Two, 6 and 8 wk treatment with quetiapine significantly reduced total and the subscales scores on the CAPS, PANSS, and CGI-S scales, in patients with psychotic PTSD. The results indicate that 8 wk of monotherapy with quetiapine reduced the majority of the psychotic and PTSD symptoms in the patients. Our present and previous data suggest that treatment-resistant psychotic PTSD patients may improve after taking atypical antipsychotics.

Emerging roles for atypical antipsychotics in chronic post-traumatic stress disorder

Post-traumatic stress disorder is an anxiety disorder that may occur after the individual is exposed to severe psychologic trauma such as combat, sexual assault, or childhood physical or sexual abuse. Chronic post-traumatic stress disorder may result in considerable psychologic pain and suffering for the individual in addition to significant functional impairment. In addition to the heterogeneity of symptoms that occur in post-traumatic stress disorder, there may also be extensive comorbidity with other anxiety disorders, mood disorders, psychotic disorders, and other psychiatric disorders. This complicates the treatment picture. Currently, accepted treatments for post-traumatic stress disorder include psychotherapy, in particular cognitive behavioral-based approaches and antidepressant medication. However, many patients are refractory to these initial treatments or have only a partial response. In light of this, may clinicians combine additional classes of psychotropic agents and different psychotherapeutic approaches to enhance treatment response. This article reviews the literature on the use of atypical antipsychotics in the treatment of post-traumatic stress disorder. Most of the research to date has involved combat veterans partially responsive or refractory to treatment, namely with antidepressants. Studies have shown improvement across post-traumatic stress disorder symptom clusters, as well as improvement in comorbid psychotic symptoms or disorders. More research is needed to confirm these recent findings and further delineate the role of atypical antipsychotics in the treatment of post-traumatic stress disorder. Currently, possible indications for their use include treatment-resistant post-traumatic stress disorder and post-traumatic stress disorder with comorbid psychotic features.

A randomized controlled trial of cognitive-behavior therapy for Cambodian refugees with treatment-resistant PTSD and panic attacks: A cross-over design

We examined the therapeutic efficacy of a culturally adapted cognitive-behavior therapy for Cambodian refugees with treatment-resistant posttraumatic stress disorder (PTSD) and comordid panic attacks. We used a cross-over design, with 20 patients in the initial treatment (IT) condition and 20 in delayed treatment (DT). Repeated measures MANOVA, Group & times; Time ANOVAs, and planned contrasts indicated significantly greater improvement in the IT condition, with large effect sizes (Cohen's d) for all outcome measures: Anxiety Sensitivity Index (d = 3.78), Clinician-Administered PTSD Scale (d = 2.17), and Symptom Checklist 90-R subscales (d = 2.77). Likewise, the severity of (culturally related) neck-focused and orthostasis-cued panic attacks, including flashbacks associated with these subtypes, improved across treatment.

P.2.102 The use of atypical antipsychotics inthe treatment-resistant combat-related posttraumatic stress disorder with psychotic features

P.2.102 The use of atypical antipsychotics inthe treatment-resistant combat-related posttraumatic stress disorder with psychotic features

Symptom patterns associated with posttraumatic stress disorder among Vietnam veterans exposed to war trauma.

The authors tested whether the relationship between traumatic stress and posttraumatic stress disorder is captured more accurately by aggregating symptoms, as in DSM-III, or differentiating them into the subtypes of denial and reexperiencing. Their findings indicate that distinguishing between the responses of denial and reexperiencing is an alternative and potentially more useful approach for understanding posttraumatic stress disorder and its origins in war trauma than the comprehensive model proposed in DSM-III. The analysis suggests that biases in the current model of posttraumatic stress disorder may lead to underestimation of its prevalence. The authors conclude that reconsideration of what constitutes the disorder is warranted.