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1.
Subst Abuse Treat Prev Policy ; 19(1): 25, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702783

RESUMO

BACKGROUND: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain. METHODS: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression. RESULTS: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%). CONCLUSION: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment. TRIAL REGISTRATION: NCT04082637.


Assuntos
Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Feminino , Masculino , Estudos Transversais , Adulto , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Fatores Sexuais , Pessoa de Meia-Idade , Trauma Psicológico/epidemiologia
2.
Behav Brain Res ; 467: 115005, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38641178

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) refers to a chronic impairing psychiatric disorder occurring after exposure to the severe traumatic event. Studies have demonstrated that medicinal cannabis oil plays an important role in neuroprotection, but the mechanism by which it exerts anti-PTSD effects remains unclear. METHODS: The chronic complex stress (CCS) simulating the conditions of long voyage stress for 4 weeks was used to establish the PTSD mice model. After that, behavioral tests were used to evaluate PTSD-like behaviors in mice. Mouse brain tissue index was detected and hematoxylin-eosin staining was used to assess pathological changes in the hippocampus. The indicators of cell apoptosis and the BDNF/TRPC6 signaling activation in the mice hippocampus were detected by western blotting or real-time quantitative reverse transcription PCR experiments. RESULTS: We established the PTSD mice model induced by CCS, which exhibited significant PTSD-like phenotypes, including increased anxiety-like and depression-like behaviors. Medicinal cannabis oil treatment significantly ameliorated PTSD-like behaviors and improved brain histomorphological abnormalities in CCS mice. Mechanistically, medicinal cannabis oil reduced CCS-induced cell apoptosis and enhanced the activation of BDNF/TRPC6 signaling pathway. CONCLUSIONS: We constructed a PTSD model with CCS and medicinal cannabis oil that significantly improved anxiety-like and depressive-like behaviors in CCS mice, which may play an anti-PTSD role by stimulating the BDNF/TRPC6 signaling pathway.


Assuntos
Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Depressão , Modelos Animais de Doenças , Hipocampo , Transdução de Sinais , Transtornos de Estresse Pós-Traumáticos , Canal de Cátion TRPC6 , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Camundongos , Transdução de Sinais/efeitos dos fármacos , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Masculino , Depressão/tratamento farmacológico , Depressão/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/metabolismo , Canal de Cátion TRPC6/metabolismo , Comportamento Animal/efeitos dos fármacos , Maconha Medicinal/farmacologia , Camundongos Endogâmicos C57BL , Apoptose/efeitos dos fármacos , Óleos de Plantas/farmacologia , Óleos de Plantas/administração & dosagem , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo
3.
Genes (Basel) ; 15(4)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38674453

RESUMO

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and the mechanisms of CBD against this disease, we conducted single-nucleus RNA sequencing (snRNA-seq) in the hippocampus of PTSD-modeled mice and CBD-treated cohorts. We constructed a mouse model by adding electric foot shocks following exposure to single prolonged stress (SPS+S) and tested the freezing time, anxiety-like behavior, and cognitive behavior. CBD was administrated before every behavioral test. The PTSD-modeled mice displayed behaviors resembling those of PTSD in all behavioral tests, and CBD treatment alleviated all of these PTSD-like behaviors (n = 8/group). Three mice with representative behavioral phenotypes were selected from each group for snRNA-seq 15 days after the SPS+S. We primarily focused on the excitatory neurons (ExNs) and inhibitory neurons (InNs), which accounted for 68.4% of the total cell annotations. A total of 88 differentially upregulated genes and 305 differentially downregulated genes were found in the PTSD mice, which were found to exhibit significant alterations in pathways and biological processes associated with fear response, synaptic communication, protein synthesis, oxidative phosphorylation, and oxidative stress response. A total of 63 overlapping genes in InNs were identified as key genes for CBD in the treatment of PTSD. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the anti-PTSD effect of CBD was related to the regulation of protein synthesis, oxidative phosphorylation, oxidative stress response, and fear response. Furthermore, gene set enrichment analysis (GSEA) revealed that CBD also enhanced retrograde endocannabinoid signaling in ExNs, which was found to be suppressed in the PTSD group. Our research may provide a potential explanation for the pathogenesis of PTSD and facilitate the discovery of novel therapeutic targets for drug development. Moreover, it may shed light on the therapeutic mechanisms of CBD.


Assuntos
Canabidiol , Modelos Animais de Doenças , Hipocampo , Transtornos de Estresse Pós-Traumáticos , Transcriptoma , Animais , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Camundongos , Canabidiol/farmacologia , Masculino , Perfilação da Expressão Gênica , Camundongos Endogâmicos C57BL
4.
J Ethnopharmacol ; 330: 118270, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38685368

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cheonwangbosimdan (CWBSD), a herbal medicine traditionally used for anxiety, insomnia, depression, and heart palpitations, has been reported to have anti-anxiety, antidepressant, cognitive improvement, and neuroprotective effects. AIM OF THE STUDY: The purpose of this study was to determine if CWBSD could affect post-traumatic stress disorder (PTSD)-like behaviors because it has prioritized clinical use over mechanism study. MATERIALS AND METHODS: A single prolonged stress (SPS) mouse model, a well-established animal model of PTSD, was used to investigate whether standardized CWBSD could mitigate PTSD-like behaviors through robust behavioral tests, including the elevated plus-maze test and marble burying test for measuring anxiety-like behaviors, the splash test, forced swimming test, and tail suspension test for evaluating depression-like behaviors, and the Y-maze test and novel object recognition test for assessing cognitive function. Additionally, a fear extinction test was employed to determine whether CWBSD might reverse fear memory extinction deficits. Amygdala tissue was isolated from SPS-treated mouse brain and subjected to Western blotting or quantitative PCR to explore mechanisms by which CWBSD could mitigate PTSD-like behaviors. RESULTS: CWBSD ameliorated emotional impairments and cognitive dysfunction in an SPS-induced PTSD-like mouse model. It also mitigated deficits in abnormal fear memory extinction. Protein expression levels of N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) and phosphorylation levels of Ca2+/calmodulin-dependent protein kinase II in the amygdala were increased in SPS model mice and normalized by CWBSD. Additionally, co-administration of CWBSD and GluN2B-containing NMDA receptor antagonist, ifenprodil, at each sub-effective dose promoted fear memory extinction. CONCLUSIONS: CWBSD can alleviate SPS-induced PTSD-like behaviors by normalizing GluN2B-containing NMDA receptor activity in the amygdala. Therefore, CWBSD could be a promising candidate for PTSD treatment with fewer adverse effects and better efficacy than existing therapies.


Assuntos
Comportamento Animal , Modelos Animais de Doenças , Receptores de N-Metil-D-Aspartato , Transtornos de Estresse Pós-Traumáticos , Animais , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/metabolismo , Masculino , Camundongos , Comportamento Animal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Medo/efeitos dos fármacos , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/psicologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38467326

RESUMO

Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Current treatments for PTSD, typically serotonin reuptake inhibitors, have limited effectiveness for patients and often cause serious adverse effects. Therefore, a novel class of treatment with better pharmacological profile is necessary. D-Pinitol has been reported to be effective for depression and anxiety disorders, but there are no reports associated with PTSD. In the present study, we investigated the effects of D-pinitol in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol. We examined the therapeutic effects of D-pinitol on emotional and cognitive impairments in the SPS mouse model. We also investigated the effects of D-pinitol on fear memory formation. Mineralocorticoid receptor transactivation assay, Western blot, and quantitative PCR were employed to investigate how D-pinitol exerts its pharmacological activities. D-Pinitol ameliorated PTSD-like behaviors in a SPS mouse model. D-Pinitol also normalized the increased mRNA expression levels and protein levels of the mineralocorticoid receptor in the amygdala. A mineralocorticoid receptor agonist reversed the effects of D-pinitol on fear extinction and recall, and the antagonistic property of D-pinitol against the mineralocorticoid receptor was confirmed in vitro. Our findings suggest that D-pinitol could serve as a potential therapeutic agent for PTSD due to its antagonistic effect on the mineralocorticoid receptor.


Assuntos
Inositol/análogos & derivados , Transtornos de Estresse Pós-Traumáticos , Camundongos , Humanos , Animais , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Medo/fisiologia , Extinção Psicológica , Receptores de Mineralocorticoides/metabolismo , Receptores de Mineralocorticoides/uso terapêutico , Modelos Animais de Doenças , Estresse Psicológico/psicologia
7.
Am J Ther ; 31(2): e141-e154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38518271

RESUMO

BACKGROUND: After becoming notorious for its use as a party drug in the 1980s, 3,4-methylenedioxy-methampetamine (MDMA), also known by its street names "molly" and "ecstasy," has emerged as a powerful treatment for post-traumatic stress disorder (PTSD). AREAS OF UNCERTAINTY: There are extensive data about the risk profile of MDMA. However, the literature is significantly biased. Animal models demonstrating neurotoxic or adverse effects used doses well beyond the range that would be expected in humans (up to 40 mg/kg in rats compared with roughly 1-2 mg/kg in humans). Furthermore, human samples often comprise recreational users who took other substances in addition to MDMA, in uncontrolled settings. THERAPEUTIC ADVANCES: Phase III clinical trials led by the Multidisciplinary Association for Psychedelic Studies (MAPS) have shown that MDMA-assisted psychotherapy has an effect size of d = 0.7-0.91, up to 2-3 times higher than the effect sizes of existing antidepressant treatments. 67%-71% of patients who undergo MDMA-assisted psychotherapy no longer meet the diagnostic criteria for PTSD within 18 weeks. We also describe other promising applications of MDMA-assisted psychotherapy for treating alcohol use disorder, social anxiety, and other psychiatric conditions. LIMITATIONS: Thus far, almost all clinical trials on MDMA have been sponsored by a single organization, MAPS. More work is needed to determine whether MDMA-assisted therapy is more effective than existing nonpharmacological treatments such as cognitive behavioral therapy. CONCLUSIONS: Phase III trials suggest that MDMA is superior to antidepressant medications for treating PTSD. Now that MAPS has officially requested the Food and Drug Administration to approve MDMA as a treatment for PTSD, legal MDMA-assisted therapy may become available as soon as 2024.


Assuntos
Alucinógenos , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Transtornos de Estresse Pós-Traumáticos , Animais , Humanos , Ratos , Antidepressivos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Alucinógenos/uso terapêutico , Metanfetamina/uso terapêutico , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Atenção Primária à Saúde , Psicoterapia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia
8.
Eur Psychiatry ; 67(1): e24, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450651

RESUMO

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.


Assuntos
Terapia Cognitivo-Comportamental , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Psiquiatras , Europa (Continente) , Antidepressivos/uso terapêutico
9.
Indian J Pharmacol ; 56(1): 20-27, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454585

RESUMO

AIMS AND OBJECTIVES: Posttraumatic stress disorder (PTSD) is a complex neuropsychiatric pathophysiology with an unmet need for safe, effective, and sustainable therapeutic modalities. Thus, the present study evaluated the effects of Withaniasomnifera (WS, Ashwagandha) on an experimental model of PTSD in rats. MATERIALS AND METHODS: Wistar rats (200-250 g) were used and time-dependent sensitization (TDS) was used as the experimental model of PTSD. Standardized WS root extract (100 and 300 mg/kg, p.o. for 15 days) was administered with TDS and their effects were observed on neurobehavioral (anxiety) and brain cytokines, corticosterone, and oxidative stress markers. RESULTS: Exposure to TDS resulted in anxiogenic behavior in the elevated plus maze (EPM) test, i.e., reductions in open arm entries and open arm time, as compared to the control group. Pretreatment with WS extract (100 and 300 mg/kg × 14 days) attenuated the TDS-induced anxiogenic activity in a dose-related manner, and these WS effects were comparable to those seen after the comparator drug fluoxetine (10 mg/kg). Assay of brain homogenates showed that TDS also resulted in elevations in brain interleukin-6 and reduction in corticosterone levels in both the hippocampus and prefrontal cortex (PFC), which were reversed after WS pretreatments. Further, WS pretreatment also reversed the TDS-induced changes in brain oxidative stress markers, namely elevated malondialdehyde and reduced glutathione levels in both the hippocampus and PFC. CONCLUSION: These results suggest that WS could have potential as a therapeutic agent for treating PTSD by attenuating anxiogenesis, neuroimmune axis activation, and oxidative stress.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Withania , Ratos , Animais , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Ratos Wistar , Corticosterona , Antioxidantes/farmacologia
10.
Nord J Psychiatry ; 78(4): 353-361, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38451197

RESUMO

BACKGROUND: Research on long-term pharmacotherapy for trauma-affected refugees is scarce. The purpose of this follow-up study of a randomised trial was to investigate the effects of sertraline compared to venlafaxine in combination with psychotherapy, 6 and 18 months after end of trial. METHOD: The primary outcome was PTSD symptoms, measured by the Harvard Trauma Questionnaire (HTQ). The secondary outcomes included: Hopkins Symptom Checklist-25 (HSCL-25), somatisation items of the Symptoms Checklist-90 (SCL), pain on a visual analogue scale, well-being on the WHO-5, Sheehan Disability Scale, Hamilton Depression and Anxiety scales and Global Assessment of Functioning. Moreover, the shorter version of the Recent Life Events (IRLE) was adopted to obtain information regarding the patients' treatment and life events between the follow-up periods. RESULTS: Out of 195 patients eligible for intention-to-treat analyses during trial, 116 participated in the 6-month follow-up and 97 participated in the 18-month follow-up. The results of our intention-to-treat analyses revealed no significant long-term differences between the groups on the primary outcome assessing PTSD symptoms (HTQ). For the secondary outcomes significant differences were found at the 18-month follow-up in favour of venlafaxine assessing symptoms of anxiety, depression and somatisation (HSCL-25 and SCL), although only in intention-to-treat and not per-protocol analyses. CONCLUSIONS: No conclusions could be drawn due to conflicting results between our intention-to-treat and per-protocol analyses.


Assuntos
Psicoterapia , Refugiados , Sertralina , Transtornos de Estresse Pós-Traumáticos , Cloridrato de Venlafaxina , Humanos , Cloridrato de Venlafaxina/uso terapêutico , Cloridrato de Venlafaxina/administração & dosagem , Feminino , Adulto , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Masculino , Seguimentos , Psicoterapia/métodos , Refugiados/psicologia , Sertralina/uso terapêutico , Terapia Combinada , Pessoa de Meia-Idade , Trauma Psicológico/terapia , Trauma Psicológico/tratamento farmacológico , Resultado do Tratamento , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico
11.
Child Adolesc Psychiatr Clin N Am ; 33(2): 193-205, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38395505

RESUMO

Trauma exposure significantly impacts sleep in children. Nightmares are common. Evidence-based therapies are superior to medications but may not always be available in acute settings. No FDA-approved medications exist for the treatment of trauma-related sleep disturbances in youth. The evidence-base for the use of medications is largely based on case reports, retrospective chart reviews, clinical opinion, and adult studies. This evidence is reviewed for a number of medications, including prazosin, trazodone, alpha-2 agonists, quetiapine, and others.


Assuntos
Transtornos do Sono-Vigília , Transtornos de Estresse Pós-Traumáticos , Migrantes , Adulto , Criança , Humanos , Adolescente , Estudos Retrospectivos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Sono , Prazosina/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etiologia
12.
Drugs ; 84(2): 149-164, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38413493

RESUMO

Post-traumatic stress disorder (PTSD) is a debilitating disorder inflicting high degrees of symptomatic and socioeconomic burdens. The development of PTSD results from a cascade of events with contributions from multiple processes and the underlying pathophysiology is complex, involving neurotransmitters, neurocircuitry, and neuroanatomical pathways. Presently, only two medications are US FDA-approved for the treatment of PTSD, both selective serotonin reuptake inhibitors (SSRIs). However, the complex underlying pathophysiology suggests a number of alternative pathways and mechanisms that may be targets for potential drug development. Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders.


Assuntos
Ketamina , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Psicoterapia/métodos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Ketamina/uso terapêutico
13.
Psychiatry Res ; 334: 115764, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38350291

RESUMO

Sleep disturbances in posttraumatic stress disorder (PTSD) are a potential target for improving PTSD severity with pharmacotherapy. TNX-102 SL is a bedtime sublingual formulation of cyclobenzaprine with potent binding and antagonist activity at 5-HT2A, α1-adrenergic, H1 histaminergic, and M1 muscarinic receptors, which play roles in the pharmacological management of sleep disturbances. This Phase 3 trial evaluated the efficacy and safety of TNX-102 SL in patients with military-related PTSD. Early and sustained improvements in sleep were associated with TNX-102 SL treatment by PROMIS Sleep Disturbance scale and Clinician Administered PTSD Scale (CAPS-5) "sleep disturbance" item, establishing a sleep quality benefit. Primary analysis comparing change from baseline in CAPS-5 total severity between TNX-102 SL and placebo at week 12 was not significant; however, week 4 was associated with an improvement. Secondary analyses showed TNX-102 SL treatment was associated with benefits on the Clinician Global Impression of Improvement at week 4 and the Patient Global Impression of Change at week 12. Time since trauma exposure was a discriminator of CAPS-5 treatment response in the subgroup ≤ 9 years since the index event. This study provides preliminary evidence that TNX-102 SL is well-tolerated and may promote recovery from PTSD by addressing sleep-related symptoms.


Assuntos
Amitriptilina/análogos & derivados , Militares , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Sono , Resultado do Tratamento , Método Duplo-Cego
14.
Mil Psychol ; 36(2): 184-191, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38377244

RESUMO

This study evaluated prospective associations of ibogaine and 5-MeO-DMT treatment for risky alcohol use and post-traumatic stress disorder (PTSD) symptoms among United States (US) Special Operations Forces Veterans (SOFV). Data were collected during standard clinical operations at pre-treatment and 1-month (1 m), 3-months (3 m), and 6-months (6 m) post-treatment in an ibogaine and 5-MeO-DMT treatment program in Mexico. Of the 86 SOFV that completed treatment, 45 met criteria for risky alcohol use at pre-treatment (mean age = 44; male = 100%; White = 91%). There was a significant reduction in alcohol use from pre-treatment (M = 7.2, SD = 2.3) to 1 m (M = 3.6; SD = 3.5) post-treatment, which remained reduced through 6 m (M = 4.0; SD = 2.9; p < .001, partial eta squared = .617). At 1 m, 24% were abstinent, 33% were non-risky drinking, and 42% were risky drinkers. At 6 m, 16% were abstinent, 31% were non-risky drinking, and 53% were risky drinkers. There were no differences between responders (abstinent/non-risky drinkers) and non-responders (risky drinkers) in demographics/clinical characteristics. However, there were significant and very large differences between responders and non-responders in PTSD symptom (p < .01, d = -3.26) and cognitive functioning change (p < .01, d = -0.99). Given these findings, future clinical trials should determine whether psychedelic-assisted therapy holds promise for individuals with complex trauma and alcohol misuse who have not been successfully treated with traditional interventions.


Assuntos
Alcoolismo , Alucinógenos , Ibogaína , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Masculino , Estados Unidos/epidemiologia , Adulto , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Veteranos/psicologia , Etanol
15.
J Clin Psychiatry ; 85(1)2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353645

RESUMO

Objective: Given the high rate of comorbid posttraumatic stress disorder (PTSD) and cannabis use, it is critical that further research be conducted to address the associated benefits and risks of cannabis use in this population. This systematic review evaluated evidence on the effects of cannabis and cannabinoids on PTSD symptoms and PTSD clusters.Data Sources: A systematic search of PubMed, PsycINFO, and EMBASE databases was performed using terms related to cannabis, cannabinoids, and PTSD. Peer-reviewed studies available online in English and published from January 1990 through February 2023 were considered.Study Selection: Included studies were experimental or observational in design, were conducted in cannabis-using patients with PTSD, used validated measures of PTSD, and were published in English.Data Extraction: Extracted information included study aims, study design, sample size and sex, comparator group, cannabis-related characteristics, psychometric instruments, and relevant clinical findings regarding overall PTSD symptoms and cluster symptoms.Results: Fourteen studies were included, 3 in a comorbid PTSD and cannabis use disorder (CUD) sample and 11 in a non-CUD sample. Of the 10 studies examining overall PTSD symptoms in a non-CUD sample, 5 suggested benefits associated with cannabis use and 5 suggested no effect or worsening of symptoms. Four studies reported benefits of cannabis for cluster B- and E-related symptoms in a non-CUD sample. All 3 studies in cannabis-using patients with a comorbid PTSD and CUD diagnosis reported risks for worsening of overall symptoms.Conclusions: This review did not find major benefits of cannabinoids in improving overall PTSD symptoms. Some benefits with regard to cluster B and E symptoms were observed. Some risks with regard to worsening suicidal ideation and violent behavior were also reported. Individuals with a comorbid CUD diagnosis may be at greater risk for negative cannabis-related PTSD outcomes. More experimental studies are needed to determine the causal effects of cannabis and cannabinoids in PTSD.


Assuntos
Canabinoides , Cannabis , Alucinógenos , Transtornos de Estresse Pós-Traumáticos , Humanos , Canabinoides/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Síndrome
16.
Front Neuroendocrinol ; 73: 101119, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38184208

RESUMO

Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited pharmacological treatments for PTSD/AUD. Neurosteroids have been implicated in the underlying neurobiological mechanisms of both PTSD and AUD and may be a target for treatment development. This review details the past ten years of research on pregnenolone, progesterone, allopregnanolone, pregnanolone, estradiol, testosterone and dehydroepiandrosterone/dehydroepiandrosterone-sulfate (DHEA/DHEA-S) in the context of PTSD and AUD, including examination of trauma/alcohol-related variables, such as stress-reactivity. Emerging evidence that exogenous pregnenolone, progesterone, and allopregnanolone may be promising, novel interventions is also discussed. Specific emphasis is placed on examining the application of sex as a biological variable in this body of literature, given that women are more susceptible to both PTSD diagnoses and stress-related alcohol consumption.


Assuntos
Alcoolismo , Neuroesteroides , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Neuroesteroides/metabolismo , Alcoolismo/metabolismo , Alcoolismo/tratamento farmacológico , Animais , Feminino , Masculino
17.
Rheumatol Int ; 44(4): 715-723, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38285107

RESUMO

Suboptimal fibromyalgia management with over-the-counter analgesics leads to deteriorated outcomes for pain and mental health symptoms especially in low-income countries hosting refugees. To examine the association between the over-the-counter analgesics and the severity of fibromyalgia, depression, anxiety and PTSD symptoms in a cohort of Syrian refugees. This is a cross-sectional study. Fibromyalgia was assessed using the patient self-report survey for the assessment of fibromyalgia. Depression was measured using the Patient Health Questionnaire-9, insomnia severity was measured using the insomnia severity index (ISI-A), and PTSD was assessed using the Davidson trauma scale (DTS)-DSM-IV. Data were analyzed from 291. Among them, 221 (75.9%) reported using acetaminophen, 79 (27.1%) reported using non-steroidal anti-inflammatory drugs (NSAIDs), and 56 (19.2%) reported receiving a prescription for centrally acting medications (CAMs). Fibromyalgia screening was significantly associated with using NSAIDs (OR 3.03, 95% CI 1.58-5.80, p = 0.001). Severe depression was significantly associated with using NSAIDs (OR 2.07, 95% CI 2.18-3.81, p = 0.02) and CAMs (OR 2.74, 95% CI 1.30-5.76, p = 0.008). Severe insomnia was significantly associated with the use of CAMs (OR 3.90, 95% CI 2.04-5.61, p < 0.001). PTSD symptoms were associated with the use of CAMs (ß = 8.99, p = 0.001) and NSAIDs (ß = 10.39, p < 0.001). Improper analgesics are associated with poor fibromyalgia and mental health outcomes, prompt awareness efforts are required to address this challenge for the refugees and health care providers.


Assuntos
Fibromialgia , Refugiados , Distúrbios do Início e da Manutenção do Sono , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Saúde Mental , Estudos Transversais , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Fibromialgia/diagnóstico , Fibromialgia/tratamento farmacológico , Síria , Depressão/tratamento farmacológico , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides , Internet
18.
Behav Neurosci ; 138(2): 73-84, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38236234

RESUMO

Psilocybe cubensis is a species of psilocybin mushroom (magic mushroom) of moderate potency whose principal active compounds are psilocybin and psilocin. Recent studies have shown the significant procognitive and mood-enhancer effects of Psilocybe cubensis. However, evidence is so limited, especially in preclinical studies. We aimed to investigate the effect of Psilocybe cubensis extract on posttraumatic stress disorder (PTSD)-like behavior, pain perception, locomotor activity, and anxiety in a rat model of PTSD. Male rats were exposed to three consecutive shocks (0.8 mA, 3 s interval) paired with three sounds broadcasted 3 s before delivering shocks (75 dB, 3 s). After 1, 3, or 21 days, freezing rate was measured in the fear-conditioning apparatus. Open filed test and hot plate were used to assess locomotor activity and anxiety, and pain subthreshold, respectively. Psilocybe cubensis was injected intraperitoneal at the dose of 25 mg/kg (single administration) before (pretrain) or after (posttrain) shocks, or before the test (pretest). Results showed psilocybin potently alleviated PTSD symptom is short- but not long-term after the induction of PTSD. Psilocybe cubensis decreased locomotor activity only in a short period after administration. Psilocybe cubensis also increased pain subthreshold and decreased anxiety. In conclusion, Psilocybe cubensis effects on PTSD-like behavior and locomotor activity seem to be remained in short-term, while Psilocybe cubensis effects on pain subthreshold and anxiety remained long-term. This is the first study evaluating the effect of Psilocybe cubensis on PTSD-like behavior in rats in three different time protocols (1, 3, and 21 days after fear conditioning). (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Modelos Animais de Doenças , Medo , Transtornos de Estresse Pós-Traumáticos , Animais , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Masculino , Medo/efeitos dos fármacos , Ratos , Psilocibina/farmacologia , Rememoração Mental/efeitos dos fármacos , Rememoração Mental/fisiologia , Ansiedade/tratamento farmacológico , Ratos Wistar
19.
Curr Med Res Opin ; 40(3): 505-516, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38258436

RESUMO

OBJECTIVE: To assess the journey of individuals from experiencing a traumatic event through onset of symptoms, diagnosis, and treatment of posttraumatic stress disorder (PTSD). METHODS: Patient- and psychiatrist-level data was collected (02/2022-05/2022) from psychiatrists who treated ≥1 civilian adult diagnosed with PTSD. Eligible charts covered civilian adults diagnosed with PTSD (2016-2020), receiving ≥1 PTSD-related treatment (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], atypical antipsychotics [AAs]), and having ≥1 medical visit in the last 12 months. Collected information included clinical and treatment characteristics surrounding the PTSD diagnosis. RESULTS: A total of 273 psychiatrists contributed data on 687 patients with PTSD (average age 36.1; 60.4% female). On average, the traumatic event and symptom onset occurred 8.7 years and 6.5 years prior to PTSD diagnosis, respectively. In the 6 months before diagnosis, 88.9% of patients had received a PTSD-related treatment. At time of diagnosis, 87.8% of patients had intrusion symptoms and 78.9% had alterations in cognition/mood; 41.2% had depressive disorder and 38.7% had anxiety. Diagnosis prompted treatment changes for 79.3% of patients, receiving treatment within 1.9 months on average, often with a first-line SSRI as either monotherapy (52.8%) or combination (24.9%). At the end of the 24-month study period, 34.4% of patients achieved psychiatrist-recorded remission. A total of 23.0% of psychiatrists expressed dissatisfaction with approved PTSD treatments, with 88.3% at least somewhat likely to prescribe AAs despite lack of FDA approval. CONCLUSION: PTSD presents heterogeneously, with an extensive journey from trauma to diagnosis with low remission rates and limited treatment options.


Assuntos
Antipsicóticos , Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Feminino , Masculino , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Ansiedade , Antipsicóticos/uso terapêutico
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