Focus (American Psychiatric Publishing)最新文献

As psychedelic compounds gain traction in psychiatry, there is a need to consider the active mechanism to explain the effect observed in randomized clinical trials. Traditionally, biological psychiatry has asked how compounds affect the causal pathways of illness to reduce symptoms and therefore focus on analysis of the pharmacologic properties. In psychedelic-assisted psychotherapy (PAP), there is debate about whether ingestion of the psychedelic alone is thought to be responsible for the clinical outcome. A question arises how the medication and psychotherapeutic intervention together might lead to neurobiological changes that underlie recovery from illness such as post-traumatic stress disorder (PTSD). This paper offers a framework for investigating the neurobiological basis of PAP by extrapolating from models used to explain how a pharmacologic intervention might create an optimal brain state during which environmental input has enduring effects. Specifically, there are developmental "critical" periods (CP) with exquisite sensitivity to environmental input; the biological characteristics are largely unknown. We discuss a hypothesis that psychedelics may remove the brakes on adult neuroplasticity, inducing a state similar to that of neurodevelopment. In the visual system, progress has been made both in identifying the biological conditions which distinguishes the CP and in manipulating the active ingredients with the idea that we might pharmacologically reopen a critical period in adulthood. We highlight ocular dominance plasticity (ODP) in the visual system as a model for characterizing CP in limbic systems relevant to psychiatry. A CP framework may help to integrate the neuroscientific inquiry with the influence of the environment both in development and in PAP. Appeared originally in Front Neurosci 2021; 15:710004.

This study investigated whether impairment persists after posttraumatic stress disorder (PTSD) has resolved. Traumatically injured patients (N = 1,035) were assessed during hospital admission and at 3 (85%) and 12 months (73%). Quality of life prior to traumatic injury was measured with the World Health Organization Quality of Life-BREF during hospitalization and at each subsequent assessment. PTSD was assessed using the Clinician-Administered PTSD Scale at 3 and 12 months. After controlling for preinjury functioning, current pain, and comorbid depression, patients whose PTSD symptoms had resolved by 12 months were more likely to have poorer quality of life in psychological (OR = 3.51), physical (OR = 10.17), social (OR = 4.54), and environmental (OR = 8.83) domains than those who never developed PTSD. These data provide initial evidence that PTSD can result in lingering effects on functional capacity even after remission of symptoms. Reprinted from Clin Psychol Sci 2016; 4:493-498, with permission from Sage. Copyright © 2016.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.

Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for Psychedelic Studies (MAPS) obtained Breakthrough Therapy Designation (BTD) from the FDA for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD on the basis of pooled analyses showing a large effect size for this treatment. This review covers data supporting BTD. In this treatment, MDMA is administered with psychotherapy in up to three monthly 8-h sessions. Participants are prepared for these sessions beforehand, and process material arising from the sessions in follow-up integrative psychotherapy sessions. Comparing data used for the approval of paroxetine and sertraline and pooled data from Phase 2 studies, MAPS demonstrated that MDMA-assisted psychotherapy constitutes a substantial improvement over available pharmacotherapies in terms of safety and efficacy. Studies of MDMA-assisted psychotherapy had lower dropout rates compared to sertraline and paroxetine trials. As MDMA is only administered under direct observation during a limited number of sessions, there is little chance of diversion, accidental or intentional overdose, or withdrawal symptoms upon discontinuation. BTD status has expedited the development of MAPS phase 3 trials occurring worldwide, leading up to a planned submission seeking FDA approval in 2021. Appeared originally in Front Psychiatry 2019; 10:650.

We summarize outcomes for several pharmacologic and neurostimulatory approaches that have been considered potential treatments to reduce suicide risk, namely, by reducing suicide deaths, attempts, and ideation in various clinical populations. Available treatments include clozapine, lithium, antidepressants, antipsychotics, electroconvulsive therapy, and transcranial magnetic stimulation. The novel repurposing of ketamine as a potential suicide risk-mitigating agent in the acute setting is also discussed. Research pathways to better understand and treat suicidal ideation and behavior from a neurobiological perspective are proposed in light of this foundation of information and the limitations and challenges inherent in suicide research. Such pathways include trials of fast-acting medications, registry approaches to identify appropriate patients for trials, identification of biomarkers, neuropsychological vulnerabilities, and endophenotypes through the study of known suicide risk-mitigating agents in hope of determining mechanisms of pathophysiology and the action of protective biological interventions. Reprinted from Am J Prev Med 2014; 47:S195-S203, with permission from Elsevier. Copyright © 2014.

Importance: According to National Patient Safety Goal 15.01.01, all individuals being treated or evaluated for behavioral health conditions as their primary reason for care in hospitals and behavioral health care organizations accredited by The Joint Commission should be screened for suicide risk using a validated tool. Existing suicide risk screens have minimal or no high-quality evidence of association with future suicide-related outcomes.

Objective: To test the association between results of the Ask Suicide-Screening Questions (ASQ) instrument in a pediatric emergency department (ED), implemented through selective and universal screening approaches, and subsequent suicide-related outcomes.

Design setting and participants: In this retrospective cohort study at an urban pediatric ED in the United States, the ASQ was administered to youths aged 8 to 18 years with behavioral and psychiatric presenting problems from March 18, 2013, to December 31, 2016 (selective condition), and then to youths aged 10 to 18 years with medical presenting problems (in addition to those aged 8-18 years with behavioral and psychiatric presenting problems) from January 1, 2017, to December 31, 2018 (universal condition).

Exposure: Positive ASQ screen at baseline ED visit.

Main outcomes and measures: The main outcomes were subsequent ED visits with suicide-related presenting problems (ie, ideation or attempts) based on electronic health records and death by suicide identified through state medical examiner records. Association with suicide-related outcomes was calculated over the entire study period using survival analyses and at 3-month follow-up for both conditions using relative risk.

Results: The complete sample was 15003 youths (7044 47.0%] male; 10209 [68.0%] black; mean [SD] age, 14.5 [3.1] years at baseline). The follow-up for the selective condition was a mean (SD) of 1133.7 (433.3) days; for the universal condition, it was 366.2 (209.2) days. In the selective condition, there were 275 suicide-related ED visits and 3 deaths by suicide. In the universal condition, there were 118 suicide-related ED visits and no deaths during the follow-up period. Adjusting for demographic characteristics and baseline presenting problem, positive ASQ screens were associated with greater risk of suicide-related outcomes among both the universal sample (hazard ratio, 6.8 [95% CI, 4.2-11.1]) and the selective sample (hazard ratio, 4.8 [95% CI, 3.5-6.5]).

Conclusions and relevance: Positive results of both selective and universal screening for suicide risk in pediatric EDs appear to be associated with subsequent suicidal behavior. Screening may be a particularly effective way to detect suicide risk among those who did not present with ideation or attempt. Future studies should examine the impact of screening in combination with o

Background: Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk.

Methods: A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations.

Results: In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation.

Conclusion: Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.Reprinted from Depress Anxiety 2022; 39:100-112, with permission from John Wiley and Sons. Copyright © 2022.