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PURPOSE: Ketamine, a noncompetitive, high-affinity antagonist of the N-methyl-d-aspartate-type glutamate receptor, has a rapid effect in patients with treatment-resistant disorder, but many patients who respond to intravenous ketamine relapse within several days. The objective of this study was to examine the long-term outcome of patients' mood 5 years after ketamine treatment. METHODS: Sixteen electroconvulsive therapy referrals received at least 1 intravenous ketamine treatment in addition to their stable antidepressant medications. Depression was evaluated using the Inventory of Depressive Symptomatology-Clinician-Rated, Hamilton Rating Scales for Depression, and Montgomery-Åsberg Depression Rating Scale. Anxiety was measured using the Hamilton Rating Scale. RESULTS: Of 16 patients treated, 6 achieved complete remission, 3 partially responded, and 7 did not respond. At baseline, all patients were treated with antidepressants, 14 patients were also treated with neuroleptics, of whom 5 patients were treated with quetiapine. The time to relapse in the 5 patients taking quetiapine was significantly longer than in patients who were taking other neuroleptics (965.83 ± 824.68 vs 80.5 ± 114.3, Z = 7.001, P = 0.0001). At the 5-year follow-up, 3 of the patients taking quetiapine maintained their remission. Overall levels of depression and anxiety at all times were improved in comparison to baseline. CONCLUSIONS: Our follow-up results suggest that the combination of quetiapine and ketamine can prolong time to relapse after ketamine treatment in patients with treatment-resistant disorder.
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Antidepresivos/farmacología , Antipsicóticos/farmacología , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Ketamina/farmacología , Fumarato de Quetiapina/farmacología , Adulto , Antidepresivos/administración & dosificación , Antipsicóticos/administración & dosificación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Ketamina/administración & dosificación , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Fumarato de Quetiapina/administración & dosificación , Inducción de Remisión , Prevención SecundariaRESUMEN
OBJECTIVES: Despite their impact on daily functioning, we have limited understanding of the executive functioning of older adults with bipolar disorder (OABD). Even less is known about the possible differences in the executive functioning of OABD and older adults with unipolar depression (OADEP). METHODS: After excluding acutely ill patients, the executive functioning of OABD was compared to that of OADEP and healthy controls (n = 22, n = 20, n = 22; respectively). Cognitive insight, a sub-domain of executive functioning, was operationalized as the discrepancy between the participants' self-reported cognitive functioning and appraisals that were made by their care partners. To complement the cognitive profiling, the groups were compared in information processing speed, verbal memory, and visual-spatial memory. RESULTS: OABD were impaired in several cognitive domains compared to healthy controls, most prominently in executive functioning and memory. OABD had poorer executive functioning and visual-spatial memory than OADEP. The findings also tentatively point toward intact cognitive insight among OABD, while OADEP seem to have a heightened level of awareness of their cognitive impairment. CONCLUSIONS: OABD have a unique profile of cognitive impairment compared to OADEP. It is characterized by a more severe cognitive impairment, accompanied by relatively intact cognitive insight. The findings may help clarify the cognitive profile of OABD and assist in the development of cognitive rehabilitation programs tailored to their needs. They should, however, be considered preliminary and await further research.
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Trastorno Bipolar , Anciano , Cognición , Función Ejecutiva , Humanos , Memoria , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: Major depressive disorder (MDD) is common in anorexia nervosa (AN), associated with worse outcome and greater suicide risk. Electroconvulsive therapy (ECT) is highly effective in the treatment of MDD refractory to antidepressive treatment. We describe a case series of female adolescents with AN receiving ECT for MDD resistant to treatment and/or with severe suicide risk. METHOD: We retrospectively analyzed the files of all 30 adolescent females hospitalized in our department because of AN between 1998 and 2017 and treated with ECT. Severity of eating disorder (ED) and depressive symptoms was retrospectively assessed using the Clinical Global Impression-Severity Scale. RESULTS: Patients were severely depressed and suicidal on admission. All were resistant to antidepressants. A significant deterioration in depression, with severe suicidality, occurred from admission to pre-ECT, with concomitant improvement in ED symptoms and increase in body mass index (BMI). Significant improvement in depressive and ED symptoms and increase in BMI occurred following ECT, continuing to discharge. Adverse effects were mostly minimal. Fifty-three percentage of the patients were rehospitalized within the first year after ECT, mostly because of deterioration of depression and attempted suicide. Several years after discharge, 46.6% of the patients had no evidence of depression, suicidality, and ED-symptomatology, and another 23% had only evidence of ED symptomatology. DISCUSSION: ECT is safe and well tolerated in AN with severe comorbid treatment resistant MDD and/or with increased suicide risk. Many AN patients undergoing ECT may be remitted at long-term follow-up.
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Anorexia Nerviosa/terapia , Depresión/terapia , Terapia Electroconvulsiva/métodos , Adolescente , Comorbilidad , Femenino , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Evidence both from animal and human studies suggests a role for dopaminergic pathways in the treatment of depression. Ropinirole, a selective agonist of dopamine D2/D3, is in use for the treatment of parkinsonism. Preliminary evidence suggests that such agonists might be useful as antidepressants. We tested whether an add-on ropinirole is an effective in depressed patients. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of add-on ropinirole in depressed patients unresponsive to at least one antidepressant. We recruited 32 unipolar and bipolar patients who remained depressed (modified 21-item Hamilton Depression Rating Scale) despite at least 4 weeks of treatment with an adequate dose of antidepressant medication. Patients received either 2 mg of oral ropinirole or placebo twice daily added on to their current medication and were evaluated weekly for 7 weeks using the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale. RESULTS: No difference in primary or secondary outcome measures was detected between the treatment and control groups. DISCUSSION: These results differ from previous studies and are unexpected in light of theoretical considerations. This may indicate that there are differences in pharmacological activity between ropinirole and other dopaminergic agents such as pramipexole.
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Antidepresivos/administración & dosificación , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Indoles/administración & dosificación , Indoles/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Body image disturbances are a prominent feature of eating disorders (EDs). Our aim was to test and evaluate a computerized assessment of body image (CABI), to compare the body image disturbances in different ED types, and to assess the factors affecting body image. The body image of 22 individuals undergoing inpatient treatment with restricting anorexia nervosa (AN-R), 22 with binge/purge AN (AN-B/P), 20 with bulimia nervosa (BN), and 41 healthy controls was assessed using the Contour Drawing Rating Scale (CDRS), the CABI, which simulated the participants' self-image in different levels of weight changes, and the Eating Disorder Inventory-2-Body Dissatisfaction (EDI-2-BD) scale. Severity of depression and anxiety was also assessed. Significant differences were found among the three scales assessing body image, although most of their dimensions differentiated between patients with EDs and controls. Our findings support the use of the CABI in the comparison of body image disturbances in patients with EDs vs. CONTROLS: Moreover, the use of different assessment tools allows for a better understanding of the differences in body image disturbances in different ED types.
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Anorexia Nerviosa/psicología , Imagen Corporal , Bulimia Nerviosa/psicología , Computadores , Autoimagen , Adolescente , Adulto , Ansiedad/complicaciones , Ansiedad/psicología , Estudios de Casos y Controles , Depresión/complicaciones , Depresión/psicología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Israel , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Perceptual closure ability is postulated to depend upon rapid transmission of magnocellular information to prefrontal cortex via the dorsal stream. In contrast, illusory contour processing requires only local interactions within primary and ventral stream visual regions, such as lateral occipital complex. Schizophrenia is associated with deficits in perceptual closure versus illusory contours processing that is hypothesized to reflect impaired magnocellular/dorsal stream. Perceptual closure and illusory contours performance was evaluated in separate groups of 12 healthy volunteers during no TMS, and during repetitive 10 Hz rTMS stimulation over dorsal stream or vertex (TMS-vertex). Perceptual closure and illusory contours were performed in 11 schizophrenia patients, no TMS was applied in these patients. TMS effects were evaluated with repeated measures ANOVA across treatments. rTMS significantly increased perceptual closure identification thresholds, with significant difference between TMS-dorsal stream and no TMS. TMS-dorsal stream also significantly reduced perceptual closure but not illusory contours accuracy. Schizophrenia patients showed increased perceptual closure identification thresholds relative to controls in the no TMS condition, but similar to controls in the TMS-dorsal stream condition. Conclusions of this study are that magnocellular/dorsal stream input is critical for perceptual closure but not illusory contours performance, supporting both trickledown theories of normal perceptual closure function, and magnocellular/dorsal stream theories of visual dysfunction in schizophrenia.
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Percepción de Cercanía , Esquizofrenia/fisiopatología , Estimulación Magnética Transcraneal , Vías Visuales , Adulto , Estudios de Casos y Controles , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: In this retrospective cross-sectional study, we evaluated the existence of psychiatric symptoms which appeared after implantation of an implantable cardioverter defibrillator (ICD). METHODS: Patients with ICDs were diagnosed using the Mini International Neuropsychiatric Interview (MINI) and were excluded if they had any psychiatric diagnosis prior to ICD implantation. Depression and anxiety were evaluated using the HAM-D and HAM-A rating scales and their attitude towards the ICD using a visual analog scale (VAS). Ninety five ICD patients with mean age of 66 years (±11.5) were recruited, 80 (84%) were men. RESULTS: Four (4%) patients were diagnosed with new-onset MDD and one patient (1%) with anxiety. Twenty seven (28%) were found to have significant depressive symptoms (HAM-D >8), without MDD diagnosis; half of them attributing these symptoms to the device. Seven (8%) patients experienced phantom shocks and had relatively higher depressive scores (HAM-D 10.3 vs. 5.8; F = 3.696; p = 0.058). The MDD rates in our study were rather consistent with those reported for cardiac patients. CONCLUSIONS: We suggest that ICD contributed little, if any, additional depressive or anxiety symptoms after implantation. We found that the overall attitude towards the device was positive and that shocks and phantom shocks were related to depressive symptoms.
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Ansiedad/psicología , Desfibriladores Implantables/psicología , Depresión/psicología , Conocimientos, Actitudes y Práctica en Salud , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
What humans look at strongly determines what they see. We show that individual differences in the tendency to look at positive stimuli are stable across time and across contents, establishing gaze positivity preference as a perceptual trait that determines the amount of positively valence stimuli individuals select for visual processing. Furthermore, we show that patients with major depressive disorder exhibit consistently low positivity preference before treatment. In a subset of patients, we also assessed the positivity preference after two months of treatment in which positivity gaze preference increased to levels similar to healthy individuals. We discuss the possible practical diagnostic applications of these findings, as well as how this general gaze-related trait may influence other behavioral and psychological aspects.
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Trastorno Depresivo Mayor , Humanos , Percepción Visual , Atención , Individualidad , FenotipoRESUMEN
BACKGROUND: Major depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs). METHOD: Sixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment. RESULTS: Patients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = -0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases. LIMITATIONS: The current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined. CONCLUSIONS: Using a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression.
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Amígdala del Cerebelo , Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Inhibidores Selectivos de la Recaptación de Serotonina , Humanos , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/diagnóstico por imagen , Amígdala del Cerebelo/fisiopatología , Amígdala del Cerebelo/diagnóstico por imagen , Masculino , Femenino , Adulto , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Persona de Mediana Edad , Biomarcadores , Estudios de Casos y Controles , Vías Nerviosas/fisiopatología , Emociones/fisiología , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagenRESUMEN
INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.
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Trastorno Obsesivo Compulsivo , Evaluación de Resultado en la Atención de Salud , Humanos , Trastorno Obsesivo Compulsivo/terapia , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/diagnóstico , Adulto , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de RemisiónRESUMEN
Recapturing meaning in life has been described as an essential element in the process of recovery from severe mental illness (SMI), but limited quantitative research still restricts our understanding of this phenomenon. The purpose of the current study was to explore the meaning in life among people with SMI and variables that may influence it such as internalized stigma and insight into the mental illness. We expected a significant negative correlation between internalized stigma and meaning in life, and that internalized stigma would moderate the relationship between insight and meaning in life. To explore these assumptions, 60 persons with SMI completed questionnaires that assessed their meaning in life, insight into their mental illness and internalized stigma, after which the data were analyzed using correlation and cluster analysis. Both hypotheses were confirmed. The mechanism behind the relationship between self-stigma and meaning in life and the theoretical and clinical implications of the moderation model are discussed.
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Trastornos Mentales/psicología , Satisfacción Personal , Autoimagen , Estereotipo , Adaptación Psicológica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estigma Social , Encuestas y CuestionariosRESUMEN
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.
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INTRODUCTION: Several studies have shown an association between panic disorder (PD) and reduced balance abilities, mainly based on functional balance scales. This pilot study aims to demonstrate the feasibility of studying balance abilities of persons with PD (PwPD) using computerized static and, for the first time, dynamic balance measurements in order to characterize balance control strategies employed by PwPD. METHODS: Twelve PwPD and 11 healthy controls were recruited. PD diagnosis was confirmed using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and the severity of symptoms was evaluated using the Hamilton Anxiety Scale (HAM-A), PD Severity Scales (PDSS), and Panic and Agoraphobia Scale (PAS). Balance was clinically assessed using the Activities-Specific Balance Confidence (ABC) scale and physically by the Mini-Balance Evaluation Systems Test (Mini-BESTest). Dizziness was evaluated using the Dizziness Handicap Inventory (DHI) scale. Postural control was evaluated statically by measuring body sway and dynamically by measuring body responses to rapid unexpected physical perturbations. RESULTS: PwPD had higher scores on the HAM-A (17.6 ± 10.3 vs. 3.0 ± 2.9; p < .001), PDSS (11.3 ± 5.1 vs. 0; p < .001), and PAS (20.3 ± 8.7 vs. 0; p < .001) questionnaires and lower scores on the balance scales compared to the controls (ABC scale: 156.2 ± 5.9 vs. 160 ± 0.0, p = .016; Mini-BESTest: 29.4 ± 2.1 vs. 31.4 ± 0.9, p = .014; DHI: 5.3 ± 4.4 vs. 0.09 ± 0.3, p < .001). In the static balance tests, PwPD showed a not-significantly smaller ellipse area of center of pressure trajectory (p = .36) and higher body sway velocity (p = .46), whereas in the dynamic balance tests, PwPD had shorter recovery time from physical perturbations in comparison to controls (2.1 ± 1.2s vs. 1.6 ± 0.9 s, p = .018). CONCLUSION: The computerized balance tests results point to an adoption of a ''postural rigidity'' strategy by the PwPD, that is, reduced dynamic adaptations in the face of postural challenges. This may reflect a nonsecure compensatory behavior. Further research is needed to delineate this strategy.
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Trastorno de Pánico , Adaptación Fisiológica , Agorafobia , Humanos , Proyectos Piloto , Equilibrio Postural/fisiologíaRESUMEN
Testosterone replacement is the most effective treatment for sexual dysfunction in hypogonadal men. Comorbid depression and antidepressant side effects may reduce its influence. The authors conducted a 6-week, double-blind, placebo-controlled clinical trial of testosterone gel versus placebo gel in men with major depressive disorder who were currently taking a serotonergic antidepressant and exhibited low or low-normal testosterone level. A total of 100 men were enrolled at 2 study sites (Boston, Massachusetts, USA, and Tel Aviv, Israel). The effects of testosterone augmentation on sexual functioning were determined using domain scores on the International Index of Erectile Function (IIEF). Complete pre- and posttrial IIEF data were available for 63 subjects. Men randomized to testosterone (n = 31) and placebo (n = 32) were similar in age, baseline testosterone levels, and baseline IIEF scores. At study termination, men randomized to placebo showed virtually no change from baseline in mean (95% CI) IIEF score (-0.7 [-6.5, 5.2]), whereas those receiving testosterone exhibited a substantial increase (15.8 [8.5, 23.1]). The estimated mean difference between groups was 16.8 [7.5, 26.1]; p = .001 by linear regression with adjustment for age and study site. There were also significant between-group differences in each of the 5 IIEF subscales, as well as on the single question involving ejaculatory ability (p ≤ .03 in all cases). Effect sizes in these comparisons remained little changed, and generally remained statistically significant, when we further adjusted for change in depression scores on the Montgomery Asberg Depression Rating Scale. It is notable that the subgroup of men with the highest baseline testosterone levels showed virtually the same improvement as those with lower levels, suggesting that the observed improvement was unlikely to be due simply to correction of hypogonadism alone. In depressed men with low or low-normal testosterone levels who continued to take serotonergic antidepressants, treatment with exogenous testosterone was associated with a significant improvement in sexual function, particularly including ejaculatory ability.
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Antidepresivos/administración & dosificación , Depresión/tratamiento farmacológico , Disfunción Eréctil/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Conducta Sexual/efectos de los fármacos , Testosterona/análogos & derivados , Adulto , Comorbilidad , Depresión/epidemiología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Disfunción Eréctil/epidemiología , Terapia de Reemplazo de Hormonas , Humanos , Israel , Masculino , Persona de Mediana Edad , Calidad de Vida , Conducta Sexual/estadística & datos numéricos , Testosterona/administración & dosificación , Estados UnidosRESUMEN
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.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , N-Metil-3,4-metilenodioxianfetamina/administración & dosificación , Trastornos por Estrés Postraumático/tratamiento farmacológico , Adulto , Terapia Combinada , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , N-Metil-3,4-metilenodioxianfetamina/efectos adversos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/patología , Resultado del TratamientoRESUMEN
Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men. We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed, hypogonadal men. For this study, we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower. We randomized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS) score. Secondary measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression Scale, and the Quality of Life Scale. Our primary analysis, using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures, failed to show a significant difference between groups (mean [95% confidence interval] 6-week change in HDRS for testosterone vs placebo, -0.4 [-2.6 to 1.8]). However, in one exploratory analysis of treatment responders, we found a possible trend in favor of testosterone on the HDRS. Our findings, combined with the conflicting data from earlier smaller studies, suggest that testosterone is not generally effective for depressed men. The possibility remains that testosterone might benefit a particular subgroup of depressed men, but if so, the characteristics of this subgroup would still need to be established.
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Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Testosterona/administración & dosificación , Adulto , Anciano , Antidepresivos/sangre , Trastorno Depresivo Mayor/sangre , Método Doble Ciego , Geles , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Calidad de Vida/psicología , Método Simple Ciego , Testosterona/sangre , Resultado del TratamientoRESUMEN
Mid-life onset male dysthymic disorder (DD) seems to be a distinct clinical condition with limited therapeutic options. Testosterone replacement is mood-enhancing and has been proposed as an antidepressant therapy, though this strategy has received limited systematic study. We therefore conducted a six-week double-blind placebo-controlled clinical trial in 23 men with DD and with low or low-normal testosterone (T) level (i.e, screening total serum testosterone <350 ng/dL). Enrolled men were randomized to receive intramuscular injections of 200 mg of testosterone cypionate or placebo every 10 days. The primary outcome measures were the Clinical Global Impression (CGI) improvement score and the 21-item Hamilton Depression Rating Scale (HDRS) score.Twenty-three patients were randomized. The mean (SD) age of the enrolled patients was 50.6 (7.0) years and that of total testosterone level was 339 (93) ng/dL. The median duration of the current dysthymic episode was 3.6 (2.3) years, and the mean (SD) HDRS was 14.0 (2.9). After the intervention, the mean HDRS score decreased significantly more in the testosterone group (7.46 [4.56]) than in the placebo group (1.8 [4.13], t21 = -3.07, P = 0.006). Remission, defined as a CGI improvement score of 1 or 2 and a final HDRS score lower than 8, was achieved by 7 (53.8%) of 13 in the testosterone group and 1 (10%) of 10 in the placebo group (P = 0.03). Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia.
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Andrógenos/uso terapéutico , Trastorno Distímico/tratamiento farmacológico , Testosterona/análogos & derivados , Adulto , Anciano , Método Doble Ciego , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Psicometría , Inducción de Remisión/métodos , Índice de Severidad de la Enfermedad , Testosterona/sangre , Testosterona/uso terapéutico , Resultado del TratamientoRESUMEN
Current treatments for Obsessive Compulsive Disorder (OCD) rely primarily on serotonergic mechanisms. However, approximately 30% of patients do not respond to serotonin reuptake inhibitors and remain chronically ill. Given the behavioral similarities between some of the compulsive behaviors in OCD and addiction, we hypothesized that the opioid antagonist naltrexone might attenuate compulsions in OCD as well. The effect of naltrexone augmentation to SRI was compared to placebo in 10 OCD outpatients who had not responded to an adequate dose of SSRI or clomipramine for at least 2 months. Participants underwent 5 weeks of treatment with naltrexone or placebo (and 1 week of tapering) in a randomized, double-blind, cross-over design. Patients were evaluated weekly using the Y-BOCS, CGI, HAM-A, and MADRS scales. A two-way repeated measures MANOVA revealed no significant effect for Y-BOCS. However, while receiving naltrexone, patients had significantly higher scores on CGI, MADRS and HAM-A as compared to placebo. The lack of significant findings on OC symptoms could be due to either ceiling effect or alternatively, due to a non-specific exacerbation on anxiety and depression but not on OC symptoms.
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Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Clomipramina/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Sinergismo Farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Escalas de Valoración Psiquiátrica , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
Several lines of accumulating evidence suggest that testosterone might be effective for the treatment of depression, especially in older men who exhibit low testosterone levels. However, despite the potential promise of this approach, the available literature of controlled studies of testosterone in depression remains extremely limited. Therefore, testosterone treatment of depression must still be considered an experimental procedure. At the present state of research, it appears that testosterone might most likely show benefit as an augmentation strategy in men who exhibit low or borderline testosterone levels and who show only a partial response to conventional antidepressants. In this article, we provide some suggested practical guidelines for the treatment of such individuals. However, it should be recognized that these suggestions are tentative and will likely require revision as additional data become available.
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Depresión/tratamiento farmacológico , Testosterona/uso terapéutico , Animales , Investigación Biomédica/métodos , Investigación Biomédica/normas , Depresión/psicología , Humanos , Masculino , Guías de Práctica Clínica como Asunto/normas , Testosterona/administración & dosificaciónRESUMEN
OBJECTIVE: Implantable Cardioverter Defibrillators (ICDs), have previously been associated with the onset of depression and anxiety. The aim of this one-year prospective study was to evaluate the rate of new onset psychopathological symptoms after elective ICD implantation. METHODS: A total of 158 consecutive outpatients who were scheduled for an elective ICD implantation were diagnosed and screened based on the Mini International Neuropsychiatric Interview (MINI). Depression and anxiety were evaluated using the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A). Patient's attitude toward the ICD device was evaluated using a Visual Analog Scale (VAS). RESULTS: Patients' mean age was 64±12.4years; 134 (85%) were men, with the majority of patients performing the procedure for reasons of 'primary prevention'. According to the MINI diagnosis at baseline, three (2%) patients suffered from major depressive disorder and ten (6%) from dysthymia. Significant improvement in HAM-D mean scores was found between baseline, three months and one year after implantation (6.50±6.4; 4.10±5.3 and 2.7±4.6, respectively F(2100)=16.42; p<0.001). There was a significantly more positive attitude toward the device over time based on the VAS score [F(2122)=53.31, p<0.001]. CONCLUSIONS: ICD implantation significantly contributes to the reduction of depressive symptoms, while the overall mindset toward the ICD device was positive and improved during the one-year follow-up.