Reviewing the Potential of Psychedelics for the Treatment of PTSD

There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search for and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, 2 psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses 4 types of compounds: 3,4-methylenedioxymethamphetamine, ketamine, classical psychedelics (e.g., psilocybin and lysergic acid diethylamide), and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research

Long-term treatment effects of imagery rehearsal therapy for nightmares in a population with diverse mental disorders

Nightmares are a common problem with debilitating consequences. Meta-analyses have revealed that imagery rehearsal therapy (IRT), in which the storyline of the recurring nightmare is changed, is the treatment of choice for nightmares. In a randomized clinical trial, we recently demonstrated that IRT was also effective in a population of patients with diverse mental disorders. In this trial, IRT showed moderate additional benefits over treatment as usual on nightmare distress, general psychopathology, and posttraumatic stress symptoms. In the current paper we report on the six- and nine month follow-up measurements of the IRT group of this trial. In the six- and nine-month follow-up the moderate improvements observed at post-treatment were sustained for all measures. This means that IRT has long-lasting effects, also in a sample with severe co-morbid psychopathology. IRT could be considered at an early stage in addition to the usual mental health treatment

Disturbed Sleep in PTSD: Thinking Beyond Nightmares

Sleep disturbances frequently co-occur with posttraumatic stress disorder (PTSD). Insomnia and nightmares are viewed as core symptoms of PTSD. Yet, relations between disturbed sleep and PTSD are far more complex: PTSD is linked to a broad range of sleep disorders and disturbed sleep markedly affects PTSD-outcome. This article provides a concise overview of the literature on prevalent comorbid sleep disorders, their reciprocal relation with PTSD and possible underlying neurophysiological mechanisms. Furthermore, diagnostic procedures, standard interventions—particularly first choice non-pharmacological therapies—and practical problems that often arise in the assessment and treatment of sleep disturbances in PTSD are described. Finally, we will present some perspectives on future multidisciplinary clinical and experimental research to develop new, more effective sleep therapies to improve both sleep and PTSD

Inflammation markers and cognitive performance in breast cancer survivors 20 years after completion of chemotherapy: a cohort study

Abstract Background Inflammation is an important candidate mechanism underlying cancer and cancer treatment-related cognitive impairment. We investigated levels of blood cell–based inflammatory markers in breast cancer survivors on average 20 years after chemotherapy and explored the relation between these markers and global cognitive performance. Methods One hundred sixty-six breast cancer survivors who received post-surgical radiotherapy and six cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy on average 20 years before enrollment were compared with 1344 cancer-free women from a population-based sample (50–80 years old). Breast cancer survivors were excluded if they used adjuvant hormonal therapy or if they developed relapse, metastasis, or second primary malignancies. Systemic inflammation status was assessed by the granulocyte-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Cognitive performance was assessed using an extensive neuropsychological test battery from which the general cognitive factor was derived to evaluate global cognitive performance. We examined the association between cancer, the general cognitive factor, and inflammatory markers using linear regression models. Results Breast cancer survivors had a lower general cognitive factor than non-exposed participants from the comparator group (mean difference = −0.21; 95% confidence interval (CI) −0.35 to −0.06). Inflammatory markers were higher in cancer survivors compared with non-exposed participants (mean difference for log(GLR) = 0.31; 95% CI 0.24 to 0.37, log(PLR) = 0.14; 95% CI 0.09 to 0.19, log(SII) = 0.31; 95% CI 0.24 to 0.39). The association between higher levels of inflammatory markers and lower general cognitive factor was statistically significant in cancer survivors but not among non-exposed participants. We found a group-by-inflammatory marker interaction; cancer survivors showed additional lower general cognitive factor per standard deviation increase in inflammatory markers (P for interaction for GLR = 0.038, PLR = 0.003, and SII = 0.033). Conclusions This is the first study to show that (1) cancer survivors have increased levels of inflammation on average 20 years after treatment and (2) these inflammatory levels are associated with lower cognitive performance. Although this association needs verification by a prospective study to determine causality, our findings can stimulate research on the role of inflammation in long-term cognitive problems and possibilities to diminish such problems

Imagery Rehearsal Therapy in Addition to Treatment as Usual for Patients With Diverse Psychiatric Diagnoses Suffering From Nightmares: A Randomized Controlled Trial

OBJECTIVE: Nightmares are associated with psychopathology and daily distress. They are highly prevalent in a psychiatric population (30%). Currently, imagery rehearsal therapy (IRT) is the treatment of choice for nightmares. With IRT, the script of the nightmare is changed into a new dream, which is imagined during the day. However, the effects of IRT in a psychiatric population remain unknown. The aim of this study was to determine the effectiveness of IRT in a heterogeneous psychiatric population. METHOD: Between January 2006 and July 2010, 90 patients with psychiatric disorders (DSM-IV-TR) were randomized to IRT or treatment-as-usual conditions. IRT consisted of 6 individual sessions added to the treatment as usual. Nightmare frequency was assessed using daily nightmare logs and the Nightmare Frequency Questionnaire. Nightmare distress was assessed using the Nightmare Distress Questionnaire and the Nightmare Effects Survey. General psychiatric symptoms were assessed using the Symptom Checklist-90 and a PTSD symptom questionnaire. Assessments were administered at the start of the trial, after the IRT and at follow-up 3 months later. RESULTS: IRT showed a moderate effect (Cohen d = 0.5-0.7, P < .05) on nightmare frequency, nightmare distress, and psychopathology measures compared with treatment as usual. These effects were largely sustained at the 3-month follow-up (Cohen d = 0.4-0.6, P < .10). CONCLUSIONS: IRT is an effective treatment for nightmares among patients with comorbid psychiatric disorders and can be employed in addition to the on-going treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00291031