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2.
PLoS One ; 15(10): e0239997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052965

RESUMO

BACKGROUND: Chronic posttraumatic stress disorder (PTSD) is a disabling condition that generates considerable morbidity, mortality, and both medical and indirect social costs. Treatment options are limited. A novel therapy using 3,4-methylenedioxymethamphetamine (MDMA) has shown efficacy in six phase 2 trials. Its cost-effectiveness is unknown. METHODS AND FINDINGS: To assess the cost-effectiveness of MDMA-assisted psychotherapy (MAP) from the health care payer's perspective, we constructed a decision-analytic Markov model to portray the costs and health benefits of treating patients with chronic, severe, or extreme, treatment-resistant PTSD with MAP. In six double-blind phase 2 trials, MAP consisted of a mean of 2.5 90-minute trauma-focused psychotherapy sessions before two 8-hour sessions with MDMA (mean dose of 125 mg), followed by a mean of 3.5 integration sessions for each active session. The control group received an inactive placebo or 25-40 mg. of MDMA, and otherwise followed the same regimen. Our model calculates net medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Efficacy was based on the pooled results of six randomized controlled phase 2 trials with 105 subjects; and a four-year follow-up of 19 subjects. Other inputs were based on published literature and on assumptions when data were unavailable. We modeled results over a 30-year analytic horizon and conducted extensive sensitivity analyses. Our model calculates expected medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Future costs and QALYs were discounted at 3% per year. For 1,000 individuals, MAP generates discounted net savings of $103.2 million over 30 years while accruing 5,553 discounted QALYs, compared to continued standard of care. MAP breaks even on cost at 3.1 years while delivering 918 QALYs. Making the conservative assumption that benefits cease after one year, MAP would accrue net costs of $7.6 million while generating 288 QALYS, or $26,427 per QALY gained. CONCLUSION: MAP provided to patients with severe or extreme, chronic PTSD appears to be cost-saving while delivering substantial clinical benefit. Third-party payers are likely to save money within three years by covering this form of therapy.


Assuntos
Análise Custo-Benefício , Alucinógenos/uso terapêutico , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , Psicoterapia/economia , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Doença Crônica , Ensaios Clínicos Fase II como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Psicoterapia/métodos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/mortalidade , Transtornos de Estresse Pós-Traumáticos/patologia , Taxa de Sobrevida
3.
PLoS One ; 15(10): e0239211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027307

RESUMO

BACKGROUND: The prevalence of psychological complaints is known to be very high in populations of asylum seekers. Despite this, data on the health care system's ability to adequately meet these high-risk populations' mental health needs are scarce. This article investigates how well the German outpatient health care system is able to detect and adequately treat them. METHODS: To this end, we combined data from a cross-sectional survey with billing data from the local social welfare office from the year 2015. Using descriptive statistics, the data of the cross-sectional study are used to quantify the psychological health care needs of asylum seekers while the secondary data analysis indicates the actual access to and extent of psychological treatment. RESULTS: In the cross-sectional study, 54% of patients were screened positive for symptoms of depression, 41% for symptoms of anxiety disorder and 18% for symptoms of Posttraumatic Stress Disorder. In total, 59% were screened positive for at least one of these three disorders. However, when contrasting these screening-based prevalences with the prevalences based on data from the health care system, a mismatch becomes apparent: According to the social welfare office's billing data, only 2.6% of asylum seekers received the diagnosis of depression, 1.4% were diagnosed with anxiety disorder and 2.9% with Posttraumatic Stress Disorder (PTSD). In combination, 4.9% were diagnosed with at least one of these three disorders. Overall, less than one tenth of asylum seekers with symptoms of depression, anxiety or PTSD received the corresponding diagnosis by the health care system. Among those who were diagnosed, about 45% received no treatment at all, while 38% were treated with drugs alone. Only 1% of all patients received psychotherapy. CONCLUSIONS: Psychological complaints are very common among asylum seekers, yet only a small proportion of this population receives the corresponding diagnoses and treatment. While various factors can contribute to these shortcomings, there is an urgent need to systematically address this deficit and introduce measures to improve mental health care for this high-risk population.


Assuntos
Saúde Mental , Refugiados/psicologia , Adolescente , Adulto , Antidepressivos/uso terapêutico , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/tratamento farmacológico , Estudos Transversais , Depressão/diagnóstico , Depressão/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia , Seguridade Social , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Inquéritos e Questionários , Adulto Jovem
4.
PLoS Med ; 17(8): e1003262, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813696

RESUMO

BACKGROUND: Complex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse, and domestic violence are increasingly prevalent. People exposed to complex traumatic events are at risk of not only posttraumatic stress disorder (PTSD) but also other mental health comorbidities. Whereas evidence-based psychological and pharmacological treatments are effective for single-event PTSD, it is not known if people who have experienced complex traumatic events can benefit and tolerate these commonly available treatments. Furthermore, it is not known which components of psychological interventions are most effective for managing PTSD in this population. We performed a systematic review and component network meta-analysis to assess the effectiveness of psychological and pharmacological interventions for managing mental health problems in people exposed to complex traumatic events. METHODS AND FINDINGS: We searched CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Published International Literature on Traumatic Stress, PsycINFO, and Science Citation Index for randomised controlled trials (RCTs) and non-RCTs of psychological and pharmacological treatments for PTSD symptoms in people exposed to complex traumatic events, published up to 25 October 2019. We adopted a nondiagnostic approach and included studies of adults who have experienced complex trauma. Complex-trauma subgroups included veterans; childhood sexual abuse; war-affected; refugees; and domestic violence. The primary outcome was reduction in PTSD symptoms. Secondary outcomes were depressive and anxiety symptoms, quality of life, sleep quality, and positive and negative affect. We included 116 studies, of which 50 were conducted in hospital settings, 24 were delivered in community settings, seven were delivered in military clinics for veterans or active military personnel, five were conducted in refugee camps, four used remote delivery via web-based or telephone platforms, four were conducted in specialist trauma clinics, two were delivered in home settings, and two were delivered in primary care clinics; clinical setting was not reported in 17 studies. Ninety-four RCTs, for a total of 6,158 participants, were included in meta-analyses across the primary and secondary outcomes; 18 RCTs for a total of 933 participants were included in the component network meta-analysis. The mean age of participants in the included RCTs was 42.6 ± 9.3 years, and 42% were male. Nine non-RCTs were included. The mean age of participants in the non-RCTs was 40.6 ± 9.4 years, and 47% were male. The average length of follow-up across all included studies at posttreatment for the primary outcome was 11.5 weeks. The pairwise meta-analysis showed that psychological interventions reduce PTSD symptoms more than inactive control (k = 46; n = 3,389; standardised mean difference [SMD] = -0.82, 95% confidence interval [CI] -1.02 to -0.63) and active control (k-9; n = 662; SMD = -0.35, 95% CI -0.56 to -0.14) at posttreatment and also compared with inactive control at 6-month follow-up (k = 10; n = 738; SMD = -0.45, 95% CI -0.82 to -0.08). Psychological interventions reduced depressive symptoms (k = 31; n = 2,075; SMD = -0.87, 95% CI -1.11 to -0.63; I2 = 82.7%, p = 0.000) and anxiety (k = 15; n = 1,395; SMD = -1.03, 95% CI -1.44 to -0.61; p = 0.000) at posttreatment compared with inactive control. Sleep quality was significantly improved at posttreatment by psychological interventions compared with inactive control (k = 3; n = 111; SMD = -1.00, 95% CI -1.49 to -0.51; p = 0.245). There were no significant differences between psychological interventions and inactive control group at posttreatment for quality of life (k = 6; n = 401; SMD = 0.33, 95% CI -0.01 to 0.66; p = 0.021). Antipsychotic medicine (k = 5; n = 364; SMD = -0.45; -0.85 to -0.05; p = 0.085) and prazosin (k = 3; n = 110; SMD = -0.52; -1.03 to -0.02; p = 0.182) were effective in reducing PTSD symptoms. Phase-based psychological interventions that included skills-based strategies along with trauma-focused strategies were the most promising interventions for emotional dysregulation and interpersonal problems. Compared with pharmacological interventions, we observed that psychological interventions were associated with greater reductions in PTSD and depression symptoms and improved sleep quality. Sensitivity analysis showed that psychological interventions were acceptable with lower dropout, even in studies rated at low risk of attrition bias. Trauma-focused psychological interventions were superior to non-trauma-focused interventions across trauma subgroups for PTSD symptoms, but effects among veterans and war-affected populations were significantly reduced. The network meta-analysis showed that multicomponent interventions that included cognitive restructuring and imaginal exposure were the most effective for reducing PTSD symptoms (k = 17; n = 1,077; mean difference = -37.95, 95% CI -60.84 to -15.16). Our use of a non-diagnostic inclusion strategy may have overlooked certain complex-trauma populations with severe and enduring mental health comorbidities. Additionally, the relative contribution of skills-based intervention components was not feasibly evaluated in the network meta-analysis. CONCLUSIONS: In this systematic review and meta-analysis, we observed that trauma-focused psychological interventions are effective for managing mental health problems and comorbidities in people exposed to complex trauma. Multicomponent interventions, which can include phase-based approaches, were the most effective treatment package for managing PTSD in complex trauma. Establishing optimal ways to deliver multicomponent psychological interventions for people exposed to complex traumatic events is a research and clinical priority.


Assuntos
Saúde Mental , Psicoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Antipsicóticos/uso terapêutico , Terapia Cognitivo-Comportamental/métodos , Comorbidade , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Transtornos de Estresse Pós-Traumáticos/epidemiologia
5.
J Clin Psychiatry ; 81(4)2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32659874

RESUMO

OBJECTIVE: A recent randomized controlled trial of repetitive transcranial magnetic stimulation (TMS) for major depressive disorder (MDD) in veterans raised the question of whether comorbid posttraumatic stress disorder (PTSD) negatively impacted the outcome of TMS in veterans. To address this, a quality database was analyzed to compare outcomes of MDD treated with TMS in veterans with and without comorbid PTSD. METHODS: The clinical outcomes of all consecutive veterans with MDD treated with TMS at the James A. Haley Veterans' Hospital as outpatients from October 2013 through September 2018 were included. Patients were initially evaluated by an experienced psychiatrist, and the diagnosis of MDD was made by clinical evaluation per DSM-IV-TR/DSM-5 criteria. At the start of treatment, after every 5 treatments, and at the end of treatment, patients were assessed with self-report and clinician-rated scales of depression. All data were abstracted from an existing quality database. RESULTS: Among the 118 patients treated with TMS for depression, 55 (47%) had comorbid PTSD and 63 (53%) had no comorbid PTSD. Response and remission rates by score on the Montgomery-Asberg Depression Rating Scale were similar between patients with PTSD (52.5% and 40.9%, respectively) and without PTSD (53.8% and 35.6%, respectively). No seizures or persistent adverse effects were observed or reported in either group. CONCLUSIONS: Comorbid PTSD did not impact the outcome of TMS for depression in this sample of veterans. Future studies should include formal ratings of PTSD to determine if the severity of PTSD affects the outcome.


Assuntos
Transtorno Depressivo Maior/terapia , Transtornos de Estresse Pós-Traumáticos/terapia , Estimulação Magnética Transcraniana , Veteranos/psicologia , Adulto , Idoso , Terapia Combinada/métodos , Bases de Dados Factuais , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicotrópicos/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Estimulação Magnética Transcraniana/efeitos adversos , Resultado do Tratamento , Adulto Jovem
6.
J Clin Psychiatry ; 81(4)2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32603560

RESUMO

OBJECTIVE: To determine whether concurrent posttraumatic stress disorder (PTSD) should affect whether to augment or switch medications when major depressive disorder (MDD) has not responded to a prior antidepressant trial. METHODS: Patients at 35 Veterans Health Administration medical centers from December 2012 to May 2015 with nonpsychotic MDD (N = 1,522) and a suboptimal response to adequate antidepressant treatment were randomly assigned to 3 "next step" treatments: switching to bupropion, augmenting the current antidepressant with bupropion, and augmenting with the antipsychotic aripiprazole. Blinded ratings with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) determined remission and response by 12 weeks and relapse after remission. Survival analyses compared treatment effects in patients with concurrent PTSD diagnosed with the Mini-International Neuropsychiatric Interview (n = 717, 47.1%) and those without PTSD (n = 805, 52.9%). RESULTS: Patients diagnosed with PTSD showed more severe depressive symptoms at baseline and were less likely to achieve either remission or response by 12 weeks. Augmentation with aripiprazole was associated with greater likelihood of achieving response (68.4%) than switching to bupropion (57.7%) in patients with PTSD (relative risk [RR] = 1.26; 95% CI, 1.01-1.59) as well as in patients without PTSD (RR = 1.29; 95% CI, 1.05-1.97) (78.9% response with aripiprazole augmentation vs 66.9% with switching to bupropion). Treatment comparisons with the group receiving augmentation with bupropion were not significant. There was no significant interaction between treatment group and PTSD on remission (P = .70), response (P = .98), or relapse (P = .15). CONCLUSIONS: Although PTSD was associated with poorer overall outcomes, the presence of concurrent PTSD among Veterans in this trial did not affect the comparative effectiveness of medications on response, remission, or relapse after initial remission. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01421342.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Adolescente , Adulto , Antidepressivos/uso terapêutico , Aripiprazol/uso terapêutico , Bupropiona/uso terapêutico , Transtorno Depressivo Maior/complicações , Resistência a Medicamentos/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Transtornos de Estresse Pós-Traumáticos/complicações , Adulto Jovem
8.
Adv Pharmacol ; 89: 261-286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616209

RESUMO

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.


Assuntos
Ketamina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Modelos Animais de Doenças , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/farmacologia , Padrões de Prática Médica , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos de Estresse Pós-Traumáticos/terapia
9.
Life Sci ; 256: 118014, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32593712

RESUMO

The age and strength of fear memory are two potential parameters that can be influenced by the impairing effects of pharmacological agents on reconsolidation of fear memory. In reconsolidation, stored information is rendered labile again after being reactivated. Pharmacological manipulations at this stage result in an inability to retrieve the fear memories, suggesting that they are erased or persistently inhibited. This fear memory impairment phenomenon can be valuable to treat post-traumatic stress disorders (PTSD). Previously ß-adrenergic antagonist propranolol has been repeatedly reported to impair fear memory in the treatment of PTSD. Atropine has also shown to disrupt memory formation. The present study was therefore designed to compare the effects of atropine and propranolol on reconsolidation of older fear memory in rat model of PTSD using Pavlovian fear conditioning apparatus. For this purpose 18 rats were taken and divided into control, atropine and propranolol groups and subjected to Pavlovian fear conditioning trials in order to develop animal model of PTSD. To evaluate the reconsolidation impairment of fear memory by atropine and propranolol, short term and long term memory was tested after reactivation of fear memory in rats. The present findings demonstrate that atropine significantly decreases fear expression. These results suggest that atropine significantly reduces the strength of fear memories and may be effective in the treatment of psychiatric disorders especially in PTSD.


Assuntos
Atropina/farmacologia , Medo/efeitos dos fármacos , Propranolol/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Memória/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Ratos , Ratos Wistar , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/metabolismo , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
10.
PLoS One ; 15(4): e0232245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353011

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe and disabling condition that may lead to functional impairment and reduced productivity. Psychological interventions have been shown to be effective in its management. The objective of this study was to assess the cost-effectiveness of a range of interventions for adults with PTSD. METHODS: A decision-analytic model was constructed to compare costs and quality-adjusted life-years (QALYs) of 10 interventions and no treatment for adults with PTSD, from the perspective of the National Health Service and personal social services in England. Effectiveness data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion. RESULTS: Eye movement desensitisation and reprocessing (EMDR) appeared to be the most cost-effective intervention for adults with PTSD (with a probability of 0.34 amongst the 11 evaluated options at a cost-effectiveness threshold of £20,000/QALY), followed by combined somatic/cognitive therapies, self-help with support, psychoeducation, selective serotonin reuptake inhibitors (SSRIs), trauma-focused cognitive behavioural therapy (TF-CBT), self-help without support, non-TF-CBT and combined TF-CBT/SSRIs. Counselling appeared to be less cost-effective than no treatment. TF-CBT had the largest evidence base. CONCLUSIONS: A number of interventions appear to be cost-effective for the management of PTSD in adults. EMDR appears to be the most cost-effective amongst them. TF-CBT has the largest evidence base. There remains a need for well-conducted studies that examine the long-term clinical and cost-effectiveness of a range of treatments for adults with PTSD.


Assuntos
Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Terapia Cognitivo-Comportamental/métodos , Análise Custo-Benefício , Inglaterra , Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Feminino , Humanos , Masculino , Psicoterapia/métodos , Anos de Vida Ajustados por Qualidade de Vida , Inibidores de Captação de Serotonina/uso terapêutico , Medicina Estatal
11.
J Med Food ; 23(5): 476-484, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32267780

RESUMO

Post-traumatic stress disorder (PTSD) is a stress-associated mental disorder characterized by an imbalance of neurotransmitters in response to traumatic events or fear. Genistein (GEN), a natural isoflavone, has been shown to exhibit neuroprotective effects. Here, we used the Morris water maze (MWM) and object recognition task (ORT) tests to examine the effects of GEN on cognitive impairment in rats after exposure to single prolonged stress (SPS), and its interaction with the serotonergic system. After exposure to SPS, male rats received GEN (2, 4, and 10 mg/kg, i.p.) for 14 days. Daily GEN administration significantly improved cognitive function in the ORT and MWM tests. GEN treatment also inhibited SPS-induced decreases in serotonin (5-HT) levels in the medial prefrontal cortex and hippocampus. These increased 5-HT concentrations in response to GEN treatment could be partially attributed to the ratio of 5-hydroxyindoleacetic acid/5-HT in the hippocampus. Our findings suggest that GEN significantly attenuates SPS-induced memory deficits in rats and may represent an effective therapeutic option for the treatment of PTSD.


Assuntos
Disfunção Cognitiva/prevenção & controle , Genisteína/uso terapêutico , Transtornos da Memória/prevenção & controle , Serotonina/sangue , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Cognição/efeitos dos fármacos , Corticosterona/sangue , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estresse Psicológico
13.
BMC Complement Med Ther ; 20(1): 70, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143600

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) is an extreme mood disorder that occurs after experiencing extreme stress, and patients with this disorder are known to accompany with symptoms of depression, anxiety, and memory impairments. Silibinin (SIL) is a natural polyphenolic flavonoid and is the main active ingredient of silymarin, which is primarily extracted from the milk thistle. Although some studies have assessed the properties of this flavonoid, the potential of SIL as a treatment for PTSD patients and its mechanisms of action have yet to be fully elucidated. METHODS: After exposure to a model of single prolonged stress (SPS), the open field test (OFT) and forced swimming test (FST), were used to investigate the effects of SIL on anxiety- and depression-like symptoms in male rats. The rats received of SIL (25, 50, and 100 mg/kg) for 14 days following exposure to SPS. RESULTS: Administration of SIL significantly improved anxiety-like behaviors in the OFT, depression-like behaviors in the FST, and freezing behavior in fear conditioning test. SIL also increased levels of serotonin in the hippocampus (Hipp) and amygdala, and enhanced expression of tryptophan hydroxylase-1 mRNA in the Hipp. The administration of SIL also inhibited SPS-induced decreases dopamine levels and increases norepinephrine levels in the Hipp. CONCLUSIONS: Taken together, the present findings suggest that SIL can be a useful therapeutic ingredient for the treatment of trauma stress-associated symptoms, including PTSD-induced anxiety and depression caused by PTSD.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Silimarina/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Transtornos de Ansiedade/prevenção & controle , Transtorno Depressivo/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo
14.
Psychopharmacology (Berl) ; 237(6): 1813-1826, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32162103

RESUMO

RATIONALE: Excessive fear and anxiety, coupled with corticolimbic dysfunction, are core features of stress- and trauma-related psychopathology, such as posttraumatic stress disorder (PTSD). Interestingly, low doses of ∆9-tetrahydrocannabinol (THC) can produce anxiolytic effects, reduce threat-related amygdala activation, and enhance functional coupling between the amygdala and medial prefrontal cortex and adjacent rostral cingulate cortex (mPFC/rACC) during threat processing in healthy adults. Together, these findings suggest the cannabinoid system as a potential pharmacological target in the treatment of excess fear and anxiety. However, the effects of THC on corticolimbic functioning in response to threat have not be investigated in adults with trauma-related psychopathology. OBJECTIVE: To address this gap, the present study tests the effects of an acute low dose of THC on corticolimbic responses to threat in three groups of adults: (1) non-trauma-exposed healthy controls (HC; n = 25), (2) trauma-exposed adults without PTSD (TEC; n = 27), and (3) trauma-exposed adults with PTSD (n = 19). METHODS: Using a randomized, double-blind, placebo-controlled, between-subjects design, 71 participants were randomly assigned to receive either THC or placebo (PBO) and subsequently completed a well-established threat processing paradigm during functional magnetic resonance imaging. RESULTS: In adults with PTSD, THC lowered threat-related amygdala reactivity, increased mPFC activation during threat, and increased mPFC-amygdala functional coupling. CONCLUSIONS: These preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.


Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Dronabinol/farmacologia , Medo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Método Duplo-Cego , Dronabinol/uso terapêutico , Medo/psicologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/psicologia
16.
Am J Health Syst Pharm ; 77(4): 288-294, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031208

RESUMO

PURPOSE: To describe the implementation and initial outcomes of a pilot interdisciplinary telehealth clinic, Allied Transitional Telehealth Encounters post-iNpatient Discharge (ATTEND), providing clinical pharmacy specialist follow-up for veterans transitioning from inpatient to outpatient mental healthcare in a Department of Veterans Affairs (DVA) hospital. SUMMARY: The ATTEND clinic's primary intervention was providing medication management appointments through clinical video telehealth (CVT) to patient discharge locations through a DVA-provided tablet. An interdisciplinary team supported care through on-unit inpatient training, secure messaging, and self-help applications. Clinical outcomes were measured through readmission rates, wait times, self-report measures, and follow-up interview at the completion of ATTEND services. Twenty patients completed on-unit training, and 16 unique patients were seen for at least 1 outpatient appointment. Inpatient readmission rates were lower for ATTEND patients than with standard care (5% versus 19%, respectively). Wait times until first postdischarge mental health appointment were reduced by a mean of 18.6 (S.D., 8.8) days. The pharmacist made medication interventions, including dosing changes, education on incorrect administration, and medication discontinuation. Self-reported psychological symptoms decreased during ATTEND participation. Post-ATTEND interviews indicated high levels of acceptance and interest in continued tablet-based care. Primary challenges included unique technological limitations and effective care coordination. CONCLUSION: The ATTEND telehealth clinic provided postinpatient mental health follow-up that was more prompt and convenient than conventional on-site appointments. Psychiatric self-report improved during ATTEND-facilitated transition to outpatient care, and the recidivism rate for ATTEND patients was lower than the general inpatient rate during the same time period.


Assuntos
Assistência Ambulatorial , Serviço de Farmácia Hospitalar/normas , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Telemedicina/normas , Veteranos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Melhoria de Qualidade , Estados Unidos , United States Department of Veterans Affairs , Adulto Jovem
17.
Depress Anxiety ; 37(1): 63-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31916660

RESUMO

BACKGROUND: Complicated grief (CG) is a bereavement-specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes. METHODS: To evaluate the impact of comorbid CG on PTSD treatment outcomes we analyzed data from a randomized trial comparing prolonged exposure, sertraline, and their combination in veterans with a primary diagnosis of combat-related PTSD (n = 194). Assessment of PTSD, trauma-related guilt, functional impairment, and suicidal ideation and behavior occurred at baseline and weeks 6, 12, and 24 during the 24-week trial. RESULTS: CG was associated with lower PTSD treatment response (odds ratio (OR) = 0.29, 95% confidence interval (CI) [0.12, 0.69], p = 0.005) and remission (OR = 0.28, 95% CI [0.11, 0.71], p = 0.007). Those with CG had greater severity of PTSD (p = 0.005) and trauma-related guilt (<0.001) at baseline and endpoint. In addition, those with CG were more likely to experience suicidal ideation during the study (CG: 35%, 14/40 vs. no CG 15%, 20/130; OR = 3.01, 95% CI [1.29, 7.02], p = 0.011). CONCLUSIONS: Comorbid CG is associated with elevated PTSD severity and independently associated with poorer endpoint treatment outcomes in veterans with combat-related PTSD, suggesting that screening and additional intervention for CG may be needed.


Assuntos
Luto , Pesar , Culpa , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Suicídio/psicologia , Veteranos/psicologia , Adulto , Distúrbios de Guerra/diagnóstico , Distúrbios de Guerra/tratamento farmacológico , Distúrbios de Guerra/psicologia , Comorbidade , Feminino , Humanos , Masculino , Programas de Rastreamento , Sertralina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Ideação Suicida
18.
J Clin Neurophysiol ; 37(1): 28-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895187

RESUMO

Posttraumatic Stress Disorder (PTSD) is a leading psychiatric disorder that mainly affects military and veteran populations but can occur in anyone affected by trauma. PTSD treatment remains difficult for physicians because most patients with PTSD do not respond to current pharmacological treatment. Psychotherapy is effective, but time consuming and expensive. Substance use disorder is often concurrent with PTSD, which leads to a significant challenge for PTSD treatment. Cannabis has recently received widespread attention for the potential to help many patient populations. Cannabis has been reported as a coping tool for patients with PTSD and preliminary legalization data indicate Cannabis use may reduce the use of more harmful drugs, such as opioids. Rigorous clinical studies of Cannabis could establish whether Cannabis-based medicines can be integrated into treatment regimens for both PTSD and substance use disorder patients.


Assuntos
Canabinoides/uso terapêutico , Maconha Medicinal/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino
19.
Arch Womens Ment Health ; 23(3): 317-329, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31385103

RESUMO

Birth experiences can be traumatic and may give rise to PTSD following childbirth (PTSD-FC). Peripartum neurobiological alterations in the oxytocinergic system are highly relevant for postpartum maternal behavioral and affective adaptions like bonding and lactation but are also implicated in the response to traumatic events. Animal models demonstrated that peripartum stress impairs beneficial maternal postpartum behavior. Early postpartum activation of the oxytocinergic system may, however, reverse these effects and thereby prevent adverse long-term consequences for both mother and infant. In this narrative review, we discuss the impact of trauma and PTSD-FC on normal endogenous oxytocinergic system fluctuations in the peripartum period. We also specifically focus on the potential of exogenous oxytocin (OT) to prevent and treat PTSD-FC. No trials of exogenous OT after traumatic childbirth and PTSD-FC were available. Evidence from non-obstetric PTSD samples and from postpartum healthy or depressed samples implies restorative functional neuroanatomic and psychological effects of exogenous OT such as improved PTSD symptoms and better mother-to-infant bonding, decreased limbic activation, and restored responsiveness in dopaminergic reward regions. Adverse effects of intranasal OT on mood and the increased fear processing and reduced top-down control over amygdala activation in women with acute trauma exposure or postpartum depression, however, warrant cautionary use of intranasal OT. Observational and experimental studies into the role of the endogenous and exogenous oxytocinergic system in PTSD-FC are needed and should explore individual and situational circumstances, including level of acute distress, intrapartum exogenous OT exposure, or history of childhood trauma.


Assuntos
Depressão Pós-Parto/tratamento farmacológico , Ocitocina/metabolismo , Parto/psicologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Parto Obstétrico/psicologia , Feminino , Humanos , Comportamento Materno , Camundongos , Ocitócicos/metabolismo , Ocitócicos/uso terapêutico , Ocitocina/uso terapêutico , Período Periparto/psicologia , Período Pós-Parto/psicologia , Gravidez , Ratos
20.
J Diet Suppl ; 17(3): 300-308, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30773961

RESUMO

Posttraumatic stress disorder (PTSD) is a serious mental health condition that affects some individuals who have witnessed or experienced a life-threatening or traumatic event. An enhanced or exaggerated acoustic startle response (ASR), reflecting heightened sensitivity to unexpected, loud sound, is a hallmark symptom of PTSD. Antidepressant medications, such as sertraline, are first-line pharmacotherapeutic agents in the treatment of PTSD, but concerns about potential side effects or taking synthetic drugs prompt discovery of naturalistic therapeutic agents. This study examined the relative effectiveness of a compound containing St. John's Wort (SJW), an herb widely prescribed for depression in Europe and sold as a dietary supplement in the United States, compared to sertraline (Zoloft) in a mouse model of PTSD. Thirty-six mice were tested for baseline ASR, then they were exposed to rats in a predator exposure paradigm known to induce PTSD-like symptoms. Mice were randomly divided into three groups for treatment (control, sertraline, SJW), and ASR was retested one week later. One-way ANOVAs found no significant group differences in ASR amplitude at baseline but a significant effect of Treatment Group after predator exposure, F(2, 33) = 5.645, p = .008, n2 = .225, when SJW-treated mice had ASR amplitudes that were significantly lower than sertraline-treated mice (by 27%) and controls (by 26%). Fecal boli counts showed a similar pattern, with lowest counts in SJW-treated mice. These results suggest SJW could be considered for studies of PTSD treatment in humans as well.


Assuntos
Hypericum , Extratos Vegetais/farmacologia , Reflexo de Sobressalto/efeitos dos fármacos , Inibidores de Captação de Serotonina/farmacologia , Sertralina/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Fitoterapia
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