Introduction: Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation.
Aims of the study: This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population.
Methods: This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy.
Results: There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate.
Conclusion: Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension.
Clinical trial registration: ChiCTR2200063642.
简介有创伤史的抑郁症患者对传统抗抑郁药的反应通常很差，预后也很差。哌唑嗪是一种α1-肾上腺素受体阻滞剂，在治疗创伤后应激障碍症状（尤其是噩梦）方面显示出良好的前景。它在治疗有创伤史的抑郁症方面的潜力值得研究：这项随机、双盲、安慰剂对照研究旨在调查小剂量哌唑嗪（0.5-1 毫克/天）作为抑郁症和创伤史患者的增强策略的疗效和耐受性。我们试图确定，与安慰剂相比，哌唑嗪能否在这一难以治疗的患者群体中迅速改善症状并提高总体治疗反应：这项随机、双盲、安慰剂对照临床研究纳入了59名首次发病或复发的单相或双相抑郁症患者。经过基本抗抑郁治疗后，他们被随机分配到哌唑嗪（0.5-1毫克/天）或安慰剂组，进行为期6周的双盲对照研究。研究采用蒙哥马利-奥斯伯格抑郁评定量表、17项汉密尔顿抑郁量表（HAMD-17）和汉密尔顿焦虑量表（HAMA）来评估疗效：结果：两组患者的人口统计学和临床症状评估结果无明显差异（P>0.05）。治疗3天后，HAMD-17和HAMA评分之间的差异有统计学意义（P 0.05）；然而，哌唑嗪组失眠或噩梦的发生率较低（3.3% vs. 20.7%，P = 0.039），但直立性低血压的发生率较高（16.7% vs. 0%，P = 0.007）。正性低血压的严重程度为轻度至中度：结论：小剂量哌唑嗪能有效改善抑郁症和外伤史患者的情绪症状，常见的不良反应为轻中度正张性低血压：临床试验注册：ChiCTR2200063642。
{"title":"Augmentation with prazosin for patients with depression and a history of trauma: A randomised, double-blind, placebo-controlled study.","authors":"Ping Guo, Yong Xu, Liang Lv, Min Feng, Yu Fang, Shanfei Cheng, Xiaoqing Xiao, Juanjuan Huang, Wei Sheng, Shikai Wang, Huanxin Chen","doi":"10.1111/acps.13763","DOIUrl":"https://doi.org/10.1111/acps.13763","url":null,"abstract":"<p><strong>Introduction: </strong>Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation.</p><p><strong>Aims of the study: </strong>This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population.</p><p><strong>Methods: </strong>This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy.</p><p><strong>Results: </strong>There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate.</p><p><strong>Conclusion: </strong>Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension.</p><p><strong>Clinical trial registration: </strong>ChiCTR2200063642.</p>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Séverine Lannoy, Henrik Ohlsson, Mallory Stephenson, Kenneth S Kendler, Jan Sundquist, Kristina Sundquist, Alexis C Edwards
Background: Suicidal behaviors are prevalent public health concerns, and we need to improve our predictive ability to better inform prevention efforts.
Methods: Using nationwide longitudinal Swedish registers, we included 344,490 males and 323,177 females born 1982-1990 with information on genetic liability and environmental exposures from birth to age 16: perinatal variables, parental psychopathology (suicide attempt, substance use disorder, major depression), family status, socioeconomic difficulties, peers' psychopathology, and school grades. We conducted sex-specific analysis and developed data-driven predictive models including risk factors that occurred between ages 0 and 16 using structural equation modeling.
Results: In both females and males, the best-fitting models reveal a complex risk pathway to suicide attempt. In females, the model indicates four direct effects on suicide attempt risk: the occurrence of suicide attempt in parents during childhood (β = 0.159, 95% CI: 0.118; 0.199) and adolescence (β = 0.115, 95% CI: 0.077; 0.153), suicide attempt in peers (β = 0.068, 95% CI: 0.057; 0.079), and low academic achievement (β = 0.166, 95% CI: 0.156; 0.175). In males, aggregate genetic liability for suicide attempt (β = 0.130, 95% CI: 0.111; 0.148), suicide attempt in parents during adolescence (β = 0.099, 95% CI: 0.074; 0.124), suicide attempt in peers (β = 0.118, 95% CI: 0.108; 0.129), and low academic achievement (β = 0.61, 95% CI: 0.152; 0.171) were related to later suicide attempt. These factors also acted as mediators to explain the association between environmental exposures in childhood and later suicide attempt.
Conclusions: These findings illustrate sex-specific pathways to suicide attempt by including risk factors that occur during the development. Results highlight the importance of genetic and family environment but also the prominent role of academic achievement.
{"title":"Prediction of suicide attempt in a Swedish population-based cohort.","authors":"Séverine Lannoy, Henrik Ohlsson, Mallory Stephenson, Kenneth S Kendler, Jan Sundquist, Kristina Sundquist, Alexis C Edwards","doi":"10.1111/acps.13761","DOIUrl":"https://doi.org/10.1111/acps.13761","url":null,"abstract":"<p><strong>Background: </strong>Suicidal behaviors are prevalent public health concerns, and we need to improve our predictive ability to better inform prevention efforts.</p><p><strong>Methods: </strong>Using nationwide longitudinal Swedish registers, we included 344,490 males and 323,177 females born 1982-1990 with information on genetic liability and environmental exposures from birth to age 16: perinatal variables, parental psychopathology (suicide attempt, substance use disorder, major depression), family status, socioeconomic difficulties, peers' psychopathology, and school grades. We conducted sex-specific analysis and developed data-driven predictive models including risk factors that occurred between ages 0 and 16 using structural equation modeling.</p><p><strong>Results: </strong>In both females and males, the best-fitting models reveal a complex risk pathway to suicide attempt. In females, the model indicates four direct effects on suicide attempt risk: the occurrence of suicide attempt in parents during childhood (β = 0.159, 95% CI: 0.118; 0.199) and adolescence (β = 0.115, 95% CI: 0.077; 0.153), suicide attempt in peers (β = 0.068, 95% CI: 0.057; 0.079), and low academic achievement (β = 0.166, 95% CI: 0.156; 0.175). In males, aggregate genetic liability for suicide attempt (β = 0.130, 95% CI: 0.111; 0.148), suicide attempt in parents during adolescence (β = 0.099, 95% CI: 0.074; 0.124), suicide attempt in peers (β = 0.118, 95% CI: 0.108; 0.129), and low academic achievement (β = 0.61, 95% CI: 0.152; 0.171) were related to later suicide attempt. These factors also acted as mediators to explain the association between environmental exposures in childhood and later suicide attempt.</p><p><strong>Conclusions: </strong>These findings illustrate sex-specific pathways to suicide attempt by including risk factors that occur during the development. Results highlight the importance of genetic and family environment but also the prominent role of academic achievement.</p>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniël P. J. van Opstal, Seyed Mostafa Kia, Lea Jakob, Metten Somers, Iris E. C. Sommer, Inge Winter‐van Rossum, René S. Kahn, Wiepke Cahn, Hugo G. Schnack
IntroductionMachine learning models have shown promising potential in individual‐level outcome prediction for patients with psychosis, but also have several limitations. To address some of these limitations, we present a model that predicts multiple outcomes, based on longitudinal patient data, while integrating prediction uncertainty to facilitate more reliable clinical decision‐making.Material and MethodsWe devised a recurrent neural network architecture incorporating long short‐term memory (LSTM) units to facilitate outcome prediction by leveraging multimodal baseline variables and clinical data collected at multiple time points. To account for model uncertainty, we employed a novel fuzzy logic approach to integrate the level of uncertainty into individual predictions. We predicted antipsychotic treatment outcomes in 446 first‐episode psychosis patients in the OPTiMiSE study, for six different clinical scenarios. The treatment outcome measures assessed at both week 4 and week 10 encompassed symptomatic remission, clinical global remission, and functional remission.ResultsUsing only baseline predictors to predict different outcomes at week 4, leave‐one‐site‐out validation AUC ranged from 0.62 to 0.66; performance improved when clinical data from week 1 was added (AUC = 0.66–0.71). For outcome at week 10, using only baseline variables, the models achieved AUC = 0.56–0.64; using data from more time points (weeks 1, 4, and 6) improved the performance to AUC = 0.72–0.74. After incorporating prediction uncertainties and stratifying the model decisions based on model confidence, we could achieve accuracies above 0.8 for ~50% of patients in five out of the six clinical scenarios.ConclusionWe constructed prediction models utilizing a recurrent neural network architecture tailored to clinical scenarios derived from a time series dataset. One crucial aspect we incorporated was the consideration of uncertainty in individual predictions, which enhances the reliability of decision‐making based on the model's output. We provided evidence showcasing the significance of leveraging time series data for achieving more accurate treatment outcome prediction in the field of psychiatry.
{"title":"Psychosis Prognosis Predictor: A continuous and uncertainty‐aware prediction of treatment outcome in first‐episode psychosis","authors":"Daniël P. J. van Opstal, Seyed Mostafa Kia, Lea Jakob, Metten Somers, Iris E. C. Sommer, Inge Winter‐van Rossum, René S. Kahn, Wiepke Cahn, Hugo G. Schnack","doi":"10.1111/acps.13754","DOIUrl":"https://doi.org/10.1111/acps.13754","url":null,"abstract":"IntroductionMachine learning models have shown promising potential in individual‐level outcome prediction for patients with psychosis, but also have several limitations. To address some of these limitations, we present a model that predicts multiple outcomes, based on longitudinal patient data, while integrating prediction uncertainty to facilitate more reliable clinical decision‐making.Material and MethodsWe devised a recurrent neural network architecture incorporating long short‐term memory (LSTM) units to facilitate outcome prediction by leveraging multimodal baseline variables and clinical data collected at multiple time points. To account for model uncertainty, we employed a novel fuzzy logic approach to integrate the level of uncertainty into individual predictions. We predicted antipsychotic treatment outcomes in 446 first‐episode psychosis patients in the OPTiMiSE study, for six different clinical scenarios. The treatment outcome measures assessed at both week 4 and week 10 encompassed symptomatic remission, clinical global remission, and functional remission.ResultsUsing only baseline predictors to predict different outcomes at week 4, leave‐one‐site‐out validation AUC ranged from 0.62 to 0.66; performance improved when clinical data from week 1 was added (AUC = 0.66–0.71). For outcome at week 10, using only baseline variables, the models achieved AUC = 0.56–0.64; using data from more time points (weeks 1, 4, and 6) improved the performance to AUC = 0.72–0.74. After incorporating prediction uncertainties and stratifying the model decisions based on model confidence, we could achieve accuracies above 0.8 for ~50% of patients in five out of the six clinical scenarios.ConclusionWe constructed prediction models utilizing a recurrent neural network architecture tailored to clinical scenarios derived from a time series dataset. One crucial aspect we incorporated was the consideration of uncertainty in individual predictions, which enhances the reliability of decision‐making based on the model's output. We provided evidence showcasing the significance of leveraging time series data for achieving more accurate treatment outcome prediction in the field of psychiatry.","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"18 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Riddhita De, Emily C. C. Smith, Janani Navagnanavel, Emily Au, Kateryna Maksyutynska, Maria Papoulias, Raghunath Singh, Kristoffer J. Panganiban, Bailey Humber, Grimur Høgnason Mohr, Mette Ødegaard Nielsen, Bjørn H. Ebdrup, Gary Remington, Sri Mahavir Agarwal, Margaret K. Hahn
BackgroundNonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic‐induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously.MethodA systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness. A meta‐analysis was also completed where applicable.ResultsWe identified two categories of studies for the meta‐analysis. Category 1 included three studies, which compared measures of AP adherence or discontinuation across BMI classes/degrees of self‐reported weight gain. When compared to normal weight individuals receiving APs or those who did not report AIWG, individuals who were either overweight or obese or reported weight gain in relation to AP use had an increased odds of AP nonadherence (OR 2.37; 95% CI 1.51–3.73; p = 0.0002). Category 2 had 14 studies which compared measures of discontinuation related to weight gain reported as an adverse effect across different APs. Olanzapine was associated with a 3.32 times (95% CI 2.32–4.74; p < 0.00001) increased likelihood of nonadherence or discontinuation when compared to other APs with lower weight gain liabilities. Similarly, APs with moderate weight gain liability (paliperidone, risperidone, and quetiapine) increased the odds of nonadherence or discontinuation by 2.25 (95% CI 1.31–3.87; p = 0.003) when compared to APs considered to have lower weight gain liability (i.e. haloperidol and aripiprazole). The qualitative summary also confirmed these findings.ConclusionThis review and meta‐analysis suggests that AIWG influences medication nonadherence/discontinuation, whereby APs with higher weight gain liability are associated with nonadherence/discontinuation. Additional studies are needed to confirm these findings.
背景抗精神病药物（AP）的不依从/停药是包括精神分裂症谱系障碍（SSD）在内的各种精神疾病患者的一个重要临床问题。方法 在MEDLINE、EMBASE、PsychINFO、CINAHL和CENTRAL等数据库中进行了系统检索，以帮助确定所有探讨严重精神疾病患者因AIWG而导致的依从性、研究辍学、抗精神病药物转换和/或停药的研究。在适用的情况下，我们还完成了一项荟萃分析。结果我们为荟萃分析确定了两类研究。第一类包括三项研究，这些研究比较了不同 BMI 等级/自我报告体重增加程度的 AP 依从性或停药情况。与接受 AP 或未报告 AIWG 的正常体重者相比，超重或肥胖或报告体重增加与 AP 使用有关的人不坚持 AP 的几率更高（OR 2.37；95% CI 1.51-3.73；P = 0.0002）。第 2 类共有 14 项研究，这些研究比较了与不同 APs 的不良反应体重增加有关的停药措施。与体重增加责任较低的其他 APs 相比，奥氮平导致不依从或停药的可能性增加了 3.32 倍 (95% CI 2.32-4.74; p < 0.00001)。同样，与被认为具有较低体重增加责任的 APs（即氟哌啶醇和阿立哌唑）相比，具有中等体重增加责任的 APs（帕潘利酮、利培酮和喹硫平）使不依从或停药的几率增加了 2.25 (95% CI 1.31-3.87; p = 0.003)。结论本综述和荟萃分析表明，AIWG 会影响药物的不依从性/停药，其中体重增加责任较高的 APs 与不依从性/停药相关。还需要更多的研究来证实这些发现。
{"title":"The impact of weight gain on antipsychotic nonadherence or discontinuation: A systematic review and meta‐analysis","authors":"Riddhita De, Emily C. C. Smith, Janani Navagnanavel, Emily Au, Kateryna Maksyutynska, Maria Papoulias, Raghunath Singh, Kristoffer J. Panganiban, Bailey Humber, Grimur Høgnason Mohr, Mette Ødegaard Nielsen, Bjørn H. Ebdrup, Gary Remington, Sri Mahavir Agarwal, Margaret K. Hahn","doi":"10.1111/acps.13758","DOIUrl":"https://doi.org/10.1111/acps.13758","url":null,"abstract":"BackgroundNonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic‐induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously.MethodA systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness. A meta‐analysis was also completed where applicable.ResultsWe identified two categories of studies for the meta‐analysis. Category 1 included three studies, which compared measures of AP adherence or discontinuation across BMI classes/degrees of self‐reported weight gain. When compared to normal weight individuals receiving APs or those who did not report AIWG, individuals who were either overweight or obese or reported weight gain in relation to AP use had an increased odds of AP nonadherence (OR 2.37; 95% CI 1.51–3.73; <jats:italic>p</jats:italic> = 0.0002). Category 2 had 14 studies which compared measures of discontinuation related to weight gain reported as an adverse effect across different APs. Olanzapine was associated with a 3.32 times (95% CI 2.32–4.74; <jats:italic>p</jats:italic> < 0.00001) increased likelihood of nonadherence or discontinuation when compared to other APs with lower weight gain liabilities. Similarly, APs with moderate weight gain liability (paliperidone, risperidone, and quetiapine) increased the odds of nonadherence or discontinuation by 2.25 (95% CI 1.31–3.87; <jats:italic>p</jats:italic> = 0.003) when compared to APs considered to have lower weight gain liability (i.e. haloperidol and aripiprazole). The qualitative summary also confirmed these findings.ConclusionThis review and meta‐analysis suggests that AIWG influences medication nonadherence/discontinuation, whereby APs with higher weight gain liability are associated with nonadherence/discontinuation. Additional studies are needed to confirm these findings.","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"42 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Alvarez‐Jimenez, J. Nicholas, L. Valentine, P. Liu, S. Mangelsdorf, S. Baker, T. Gilbertson, G. O'Loughlin, C. McEnery, P. D. McGorry, J. F. Gleeson, S. P. Cross
BackgroundYouth mental health (YMH) services have been established internationally to provide timely, age‐appropriate, mental health treatment and improve long‐term outcomes. However, YMH services face challenges including long waiting times, limited continuity of care, and time‐bound support. To bridge this gap, MOST was developed as a scalable, blended, multi‐modal digital platform integrating real‐time and asynchronous clinician‐delivered counselling; interactive psychotherapeutic content; vocational support; peer support, and a youth‐focused online community. The implementation of MOST within Australian YMH services has been publicly funded.ObjectiveThe primary aim of this study was to evaluate the real‐world engagement, outcomes, and experience of MOST during the first 32 months of implementation.MethodYoung people from participating YMH services were referred into MOST. Engagement metrics were derived from platform usage. Symptom and satisfaction measures were collected at baseline, 6, and 12 (primary endpoint) weeks. Effect sizes were calculated for the primary outcomes of depression and anxiety and secondary outcomes of psychological distress and wellbeing.ResultsFive thousand seven hundred and two young people from 262 clinics signed up and used MOST at least once. Young people had an average of 19 login sessions totalling 129 min over the first 12 weeks of use, with 71.7% using MOST for at least 14 days, 40.1% for 12 weeks, and 18.8% for 24 weeks. There was a statistically significant, moderate improvement in depression and anxiety at 12 weeks as measured by the PHQ4 across all users irrespective of treatment stage (d = 0.41, 95% CI 0.35–0.46). Satisfaction levels were high, with 93% recommending MOST to a friend. One thousand one hundred and eighteen young people provided written feedback, of which 68% was positive and 31% suggested improvement.ConclusionsMOST is a highly promising blended digital intervention with potential to address the limitations and enhance the impact of YMH services.
{"title":"A national evaluation of a multi‐modal, blended, digital intervention integrated within Australian youth mental health services","authors":"M. Alvarez‐Jimenez, J. Nicholas, L. Valentine, P. Liu, S. Mangelsdorf, S. Baker, T. Gilbertson, G. O'Loughlin, C. McEnery, P. D. McGorry, J. F. Gleeson, S. P. Cross","doi":"10.1111/acps.13751","DOIUrl":"https://doi.org/10.1111/acps.13751","url":null,"abstract":"BackgroundYouth mental health (YMH) services have been established internationally to provide timely, age‐appropriate, mental health treatment and improve long‐term outcomes. However, YMH services face challenges including long waiting times, limited continuity of care, and time‐bound support. To bridge this gap, MOST was developed as a scalable, blended, multi‐modal digital platform integrating real‐time and asynchronous clinician‐delivered counselling; interactive psychotherapeutic content; vocational support; peer support, and a youth‐focused online community. The implementation of MOST within Australian YMH services has been publicly funded.ObjectiveThe primary aim of this study was to evaluate the real‐world engagement, outcomes, and experience of MOST during the first 32 months of implementation.MethodYoung people from participating YMH services were referred into MOST. Engagement metrics were derived from platform usage. Symptom and satisfaction measures were collected at baseline, 6, and 12 (primary endpoint) weeks. Effect sizes were calculated for the primary outcomes of depression and anxiety and secondary outcomes of psychological distress and wellbeing.ResultsFive thousand seven hundred and two young people from 262 clinics signed up and used MOST at least once. Young people had an average of 19 login sessions totalling 129 min over the first 12 weeks of use, with 71.7% using MOST for at least 14 days, 40.1% for 12 weeks, and 18.8% for 24 weeks. There was a statistically significant, moderate improvement in depression and anxiety at 12 weeks as measured by the PHQ4 across all users irrespective of treatment stage (<jats:italic>d</jats:italic> = 0.41, 95% CI 0.35–0.46). Satisfaction levels were high, with 93% recommending MOST to a friend. One thousand one hundred and eighteen young people provided written feedback, of which 68% was positive and 31% suggested improvement.ConclusionsMOST is a highly promising blended digital intervention with potential to address the limitations and enhance the impact of YMH services.","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"73 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robin Olfermann, Sabine Schlegel, Anna Vogelsang, Ulrich Ebner-Priemer, Almut Zeeck, Markus Reichert
Introduction: Many patients with eating disorders (EDs) engage in excessive and compulsive physical activity (pathological exercise, PE) to regulate negative mood or to "burn calories." PE can lead to negative health consequences. Non-exercise activity (NEA) bears the potential to serve as intervention target to counteract PE and problematic eating behaviors since it has been associated with positive mood effects. However, to date, there is no investigation on whether the positive link between NEA and mood seen in the healthy translates to patients with ED.
Material and methods: To study potential associations of NEA and mood in ED, we subjected 29 ED-patients and 35 healthy controls (HCs) to an ambulatory assessment study across 7 days. We measured NEA via accelerometers and repeatedly assessed mood on electronic smartphone diaries via a mixed sampling strategy based on events, activity and time. Within- and between-subject effects of NEA on mood, PE as moderator, and the temporal course of effects were analyzed via multilevel modeling.
Results: NEA increased valence (β = 2.12, p < 0.001) and energetic arousal (β = 4.02, p < 0.001) but showed no significant effect on calmness. The effects of NEA on energetic arousal where significantly stronger for HCs (βHC = 6.26, p < 0.001) than for EDs (βED = 4.02, p < 0.001; βinteraction = 2.24, p = 0.0135). Effects of NEA were robust across most timeframes of NEA and significantly moderated by PE, that is, Lower PE levels exhibited stronger NEA effects on energetic arousal.
Conclusion: Patients with ED and HC show an affective benefit from NEA, partly depending on the level of PE. If replicated in experimental daily life studies, this evidence may pave the way towards expedient NEA interventions to cope with negative mood. Interventions could be especially promising if delivered as Just-in-time adaptive interventions (JITAIs) and should be tailored according to the PE level.
导言：许多饮食失调症（EDs）患者为了调节负面情绪或 "燃烧卡路里"，会进行过度和强迫性的体育锻炼（病理性锻炼，PE）。病理性运动会对健康造成负面影响。由于非运动性活动（NEA）与积极情绪效应相关，因此有可能成为抵制 PE 和问题饮食行为的干预目标。然而，迄今为止，尚无研究表明，健康人的 NEA 与情绪之间的积极联系是否也适用于 ED 患者：为了研究 NEA 与 ED 患者情绪之间的潜在联系，我们对 29 名 ED 患者和 35 名健康对照者（HCs）进行了为期 7 天的流动评估研究。我们通过加速度计测量NEA，并通过基于事件、活动和时间的混合采样策略，在电子智能手机日记上反复评估情绪。通过多层次建模分析了NEA对情绪的受试者内和受试者间效应、作为调节因素的PE以及效应的时间过程：NEA 增加了情绪（β = 2.12，p HC = 6.26，p ED = 4.02，p 交互作用 = 2.24，p = 0.0135）。NEA的效应在NEA的大多数时间范围内都是稳健的，并受到PE的显著调节，即较低的PE水平表现出较强的NEA对精力唤醒的效应：结论：ED和HC患者可从NEA中获得情感益处，部分取决于PE水平。如果在日常生活实验研究中得到证实，这一证据可能会为采取便捷的 NEA 干预措施来应对负面情绪铺平道路。如果以适时适应性干预（JITAIs）的方式进行干预，并根据 PE 水平量身定制干预方案，则会特别有前景。
{"title":"Relationship between nonexercise activity and mood in patients with eating disorders.","authors":"Robin Olfermann, Sabine Schlegel, Anna Vogelsang, Ulrich Ebner-Priemer, Almut Zeeck, Markus Reichert","doi":"10.1111/acps.13757","DOIUrl":"https://doi.org/10.1111/acps.13757","url":null,"abstract":"<p><strong>Introduction: </strong>Many patients with eating disorders (EDs) engage in excessive and compulsive physical activity (pathological exercise, PE) to regulate negative mood or to \"burn calories.\" PE can lead to negative health consequences. Non-exercise activity (NEA) bears the potential to serve as intervention target to counteract PE and problematic eating behaviors since it has been associated with positive mood effects. However, to date, there is no investigation on whether the positive link between NEA and mood seen in the healthy translates to patients with ED.</p><p><strong>Material and methods: </strong>To study potential associations of NEA and mood in ED, we subjected 29 ED-patients and 35 healthy controls (HCs) to an ambulatory assessment study across 7 days. We measured NEA via accelerometers and repeatedly assessed mood on electronic smartphone diaries via a mixed sampling strategy based on events, activity and time. Within- and between-subject effects of NEA on mood, PE as moderator, and the temporal course of effects were analyzed via multilevel modeling.</p><p><strong>Results: </strong>NEA increased valence (β = 2.12, p < 0.001) and energetic arousal (β = 4.02, p < 0.001) but showed no significant effect on calmness. The effects of NEA on energetic arousal where significantly stronger for HCs (β<sub>HC</sub> = 6.26, p < 0.001) than for EDs (β<sub>ED</sub> = 4.02, p < 0.001; β<sub>interaction</sub> = 2.24, p = 0.0135). Effects of NEA were robust across most timeframes of NEA and significantly moderated by PE, that is, Lower PE levels exhibited stronger NEA effects on energetic arousal.</p><p><strong>Conclusion: </strong>Patients with ED and HC show an affective benefit from NEA, partly depending on the level of PE. If replicated in experimental daily life studies, this evidence may pave the way towards expedient NEA interventions to cope with negative mood. Interventions could be especially promising if delivered as Just-in-time adaptive interventions (JITAIs) and should be tailored according to the PE level.</p>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Serra-Navarro, Derek Clougher, Brisa Solé, Jose Sánchez-Moreno, Ana González-Pinto, Esther Jiménez, Benedikt L. Amann, Vicent Balanzá-Martínez, Rafael Tabarés-Seisdedos, Celso Arango, Vivian Accardo, María Paz García-Portilla, Ángela Ibáñez, José Manuel Crespo, José Luis Ayuso-Mateos, Silvia Amoretti, Carla Torrent, Anabel Martínez-Aran, Eduard Vieta, CIBERSAM Functional Remediation Group
Background
Functional recovery remains a core clinical objective for patients with bipolar disorder (BD). Sociodemographic, clinical, and neurocognitive variables are associated with long-term functional impairment, yet the impact of sex differences is unclear. Functional remediation (FR) is a validated intervention aimed at achieving functional recovery in BD. The present study assessed the effect of sex differences of FR on psychosocial functioning at post-treatment (6-months) and 12-month follow-up (FUP). To the best of our knowledge, this is the first study to explore the role of sex as a factor in the efficacy of FR.
Methods
157 participants with BD were randomly assigned to either FR (N = 77) or treatment as usual group (80). Clinical, sociodemographic, neuropsychological, and functional data were obtained using a comprehensive assessment battery. Sex differences were explored via a general linear model (GLM) for repeated measures to compare the effect of sex on the intervention over time (6 months and FUP).
Results
Results demonstrated that FR benefits both sexes, males (p = 0.001; d’ = 0.88) and females (p = 0.04; d’ = 0.57), at 6 months suggesting a generalized functional improvement. Conversely, at 12-month FUP sex differences were observed only in males (p = 0.005; d’ = 0.68).
Conclusions
FR is a beneficial intervention for males and females after treatment, suggesting that there are no relevant distinct needs. Females may benefit from ongoing psychosocial functioning booster sessions after the intervention to maintain original improvements. Future research exploring sex differences could help to identify strategies to offer personalized FR intervention approaches in individuals with BD.
{"title":"The impact of sex in the effectiveness of functional remediation in bipolar disorder","authors":"Maria Serra-Navarro, Derek Clougher, Brisa Solé, Jose Sánchez-Moreno, Ana González-Pinto, Esther Jiménez, Benedikt L. Amann, Vicent Balanzá-Martínez, Rafael Tabarés-Seisdedos, Celso Arango, Vivian Accardo, María Paz García-Portilla, Ángela Ibáñez, José Manuel Crespo, José Luis Ayuso-Mateos, Silvia Amoretti, Carla Torrent, Anabel Martínez-Aran, Eduard Vieta, CIBERSAM Functional Remediation Group","doi":"10.1111/acps.13748","DOIUrl":"10.1111/acps.13748","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Functional recovery remains a core clinical objective for patients with bipolar disorder (BD). Sociodemographic, clinical, and neurocognitive variables are associated with long-term functional impairment, yet the impact of sex differences is unclear. Functional remediation (FR) is a validated intervention aimed at achieving functional recovery in BD. The present study assessed the effect of sex differences of FR on psychosocial functioning at post-treatment (6-months) and 12-month follow-up (FUP). To the best of our knowledge, this is the first study to explore the role of sex as a factor in the efficacy of FR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>157 participants with BD were randomly assigned to either FR (<i>N</i> = 77) or treatment as usual group (80). Clinical, sociodemographic, neuropsychological, and functional data were obtained using a comprehensive assessment battery. Sex differences were explored via a general linear model (GLM) for repeated measures to compare the effect of sex on the intervention over time (6 months and FUP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results demonstrated that FR benefits both sexes, males (<i>p</i> = 0.001; d’ = 0.88) and females (<i>p</i> = 0.04; d’ = 0.57), at 6 months suggesting a generalized functional improvement. Conversely, at 12-month FUP sex differences were observed only in males (<i>p</i> = 0.005; d’ = 0.68).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FR is a beneficial intervention for males and females after treatment, suggesting that there are no relevant distinct needs. Females may benefit from ongoing psychosocial functioning booster sessions after the intervention to maintain original improvements. Future research exploring sex differences could help to identify strategies to offer personalized FR intervention approaches in individuals with BD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"150 6","pages":"543-561"},"PeriodicalIF":5.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Jelovac, Christopher Mohan, Emma Whooley, Anna Igoe, Cathal McCaffrey, Declan M McLoughlin
Objective: Childhood maltreatment is associated with less favourable treatment outcomes with pharmacotherapy and psychotherapy for depression. It is unknown whether this increased risk of treatment resistance in maltreated individuals extends to electroconvulsive therapy (ECT).
Methods: This retrospective cohort study included 501 consecutive adult referrals for an acute course of twice-weekly ECT for unipolar or bipolar depression at an academic inpatient centre in Ireland between 2016 and 2024. Retrospectively reported physical and sexual childhood maltreatment were assessed on hospital admission. Response was defined as a score of 1 or 2 and remission was defined as a score of 1 on the Clinical Global Impression - Improvement scale 1-3 days after final ECT session. Logistic regression analyses were used to examine the associations between childhood maltreatment and ECT nonresponse and nonremission, adjusting for covariates. Mediation analyses were conducted to explore the role of psychiatric comorbidities, persistent depressive symptoms lasting 2 years or more in the current episode, and baseline depression severity.
Results: Compared to the group with no childhood maltreatment, the childhood maltreatment group had similar odds of ECT nonresponse (adjusted odds ratio = 1.47, 95% CI = 0.85-2.53) but significantly elevated odds of ECT nonremission (adjusted odds ratio = 3.75, 95% CI = 1.80-7.81). In a mediation analysis, presence of persistent depressive symptoms mediated 7.4% of the total effect of childhood maltreatment on ECT nonremission.
Conclusion: Individuals with exposure to childhood maltreatment may be less likely to achieve full remission following a course of ECT.
{"title":"Childhood maltreatment and outcomes following electroconvulsive therapy in adults with depression.","authors":"Ana Jelovac, Christopher Mohan, Emma Whooley, Anna Igoe, Cathal McCaffrey, Declan M McLoughlin","doi":"10.1111/acps.13756","DOIUrl":"https://doi.org/10.1111/acps.13756","url":null,"abstract":"<p><strong>Objective: </strong>Childhood maltreatment is associated with less favourable treatment outcomes with pharmacotherapy and psychotherapy for depression. It is unknown whether this increased risk of treatment resistance in maltreated individuals extends to electroconvulsive therapy (ECT).</p><p><strong>Methods: </strong>This retrospective cohort study included 501 consecutive adult referrals for an acute course of twice-weekly ECT for unipolar or bipolar depression at an academic inpatient centre in Ireland between 2016 and 2024. Retrospectively reported physical and sexual childhood maltreatment were assessed on hospital admission. Response was defined as a score of 1 or 2 and remission was defined as a score of 1 on the Clinical Global Impression - Improvement scale 1-3 days after final ECT session. Logistic regression analyses were used to examine the associations between childhood maltreatment and ECT nonresponse and nonremission, adjusting for covariates. Mediation analyses were conducted to explore the role of psychiatric comorbidities, persistent depressive symptoms lasting 2 years or more in the current episode, and baseline depression severity.</p><p><strong>Results: </strong>Compared to the group with no childhood maltreatment, the childhood maltreatment group had similar odds of ECT nonresponse (adjusted odds ratio = 1.47, 95% CI = 0.85-2.53) but significantly elevated odds of ECT nonremission (adjusted odds ratio = 3.75, 95% CI = 1.80-7.81). In a mediation analysis, presence of persistent depressive symptoms mediated 7.4% of the total effect of childhood maltreatment on ECT nonremission.</p><p><strong>Conclusion: </strong>Individuals with exposure to childhood maltreatment may be less likely to achieve full remission following a course of ECT.</p>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To evaluate the association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage.
Material and Methods
This nested case–control study used a large Japanese administrative database. Pregnancy onset and outcomes were estimated using previously reported algorithms, classifying cases as women becoming pregnant between 2013 and 2022 and ending in a miscarriage. Controls were randomly selected from the entire pregnancy cohort by risk-set sampling with replacement and were individually matched to the cases (3:1). The association between exposure to atypical antipsychotics and risk of miscarriage was assessed using conditional logistic regression adjusted for confounders. The association between benzodiazepine exposure and the risk of miscarriage was assessed as a positive control.
Results
In the cohort, 44,118 patients were matched with 132,317 controls. The mean ages (standard deviations) of the case and control groups were 33.3 (5.7) and 33.2 (5.5) years, respectively. The prevalence of atypical antipsychotics was 0.5% in both groups. Aripiprazole is an individual antipsychotic with the highest prescription prevalence. The adjusted odds ratios (aOR) for miscarriage were 0.966 (95% confidence interval [CI], 0.796–1.173) for atypical antipsychotics and 0.998 (0.784–1.269) for aripiprazole. A higher aOR (1.431, 95% CI 1.303–1.573) suggested an association with benzodiazepines. A sensitivity analysis that limited the population to women diagnosed with schizophrenia alone did not suggest an association between atypical antipsychotics and the risk of miscarriage.
Conclusions
The results of this study do not suggest an association between exposure to atypical antipsychotics during pregnancy and the risk of miscarriage.
{"title":"Association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage","authors":"Tomofumi Ishikawa, Takamasa Sakai, Noriyuki Iwama, Ryo Obara, Kei Morishita, Motohiko Adomi, Aoi Noda, Mami Ishikuro, Saya Kikuchi, Natsuko Kobayashi, Hiroaki Tomita, Masatoshi Saito, Hidekazu Nishigori, Shinichi Kuriyama, Nariyasu Mano, Taku Obara","doi":"10.1111/acps.13755","DOIUrl":"10.1111/acps.13755","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>This nested case–control study used a large Japanese administrative database. Pregnancy onset and outcomes were estimated using previously reported algorithms, classifying cases as women becoming pregnant between 2013 and 2022 and ending in a miscarriage. Controls were randomly selected from the entire pregnancy cohort by risk-set sampling with replacement and were individually matched to the cases (3:1). The association between exposure to atypical antipsychotics and risk of miscarriage was assessed using conditional logistic regression adjusted for confounders. The association between benzodiazepine exposure and the risk of miscarriage was assessed as a positive control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the cohort, 44,118 patients were matched with 132,317 controls. The mean ages (standard deviations) of the case and control groups were 33.3 (5.7) and 33.2 (5.5) years, respectively. The prevalence of atypical antipsychotics was 0.5% in both groups. Aripiprazole is an individual antipsychotic with the highest prescription prevalence. The adjusted odds ratios (aOR) for miscarriage were 0.966 (95% confidence interval [CI], 0.796–1.173) for atypical antipsychotics and 0.998 (0.784–1.269) for aripiprazole. A higher aOR (1.431, 95% CI 1.303–1.573) suggested an association with benzodiazepines. A sensitivity analysis that limited the population to women diagnosed with schizophrenia alone did not suggest an association between atypical antipsychotics and the risk of miscarriage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results of this study do not suggest an association between exposure to atypical antipsychotics during pregnancy and the risk of miscarriage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"150 6","pages":"562-572"},"PeriodicalIF":5.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Monoamine oxidase inhibitors (MAOIs) were the first licensed antidepressants, they were discovered serendipitously, during a trial of iproniazid in patients with tuberculosis in the 1950s. Iproniazid appeared to have a “psychic energizing effect,” which resulted in the improvement of depressive symptoms in some tuberculosis patients,<span><sup>1</sup></span> around that time, iproniazid was shown to inhibit the MAO enzyme. Iproniazid was approved as an antidepressant, and this led to the development of several other MAOIs. Brain neurotransmitter levels are inactivated by MAO-A (serotonin, norepinephrine, dopamine) and MAO-B (dopamine) isoenzymes. Inhibition of the MAO enzyme leads to an increasing synaptic availability of these monoamines. In addition, tranylcypromine is similar in chemical structure to amphetamine and shares its dopamine-releasing and stimulant-like effects. Tranylcypromine and phenelzine are the most frequently used non-selective MAOIs, which bind the MAO enzyme irreversibly, and deactivate it permanently. Moclobemide is a selective MAO-A inhibitor, and enters into a reversible binding to the enzyme. Tranylcypromine and Phenelzine were widely prescribed until the late 1960s. The use of MAOIs has declined dramatically, as stated in their network meta-analysis by Gimenez-Palomo et al.<span><sup>2</sup></span> The historical perspective is important in understanding this decline.</p><p>In the 1960s it was not well understood that MAOIs inhibit the breakdown of tyramine, and that excessive tyramine intake when using an MAOI, can lead to a hypertensive crisis. A series of initially unexplained hypertensive crises actually occurred, some even resulting in stroke. The cause of this “cheese reaction” was uncovered in the late 1960s, but the fear for the hypertensive reaction remained. Furthermore, in one of the first large randomized clinical trials in psychiatry,<span><sup>3</sup></span> which included 260 depressed patients, both ECT and imipramine appeared to be effective, whereas phenelzine and placebo were not. In hindsight, one may well argue, that both the duration of treatment with phenelzine (4 weeks) and its dose (maximum 60 mg daily) were insufficient, therefore, phenelzine fell short of its full efficacy potential. Subsequently, MAOIs were regarded as not very effective and dangerous antidepressant drugs. This perception influenced physicians to strongly favor tricyclic antidepressants (TCAs) over MAOIs. Usage of MAOIs further declined, following the development of newer antidepressants, especially the selective serotonin reuptake inhibitors (SSRIs). Concerns about the safety profile of MAOIs, including potentially dangerous drug–drug interactions, which could result in serotonin syndrome, and the risk of a hypertensive crisis restricted their use. Furthermore, the use of MAOIs was not promoted by any pharmaceutical company.</p><p>In several countries the number of prescriptions of MAOIs is extremely low: about 500 patie
{"title":"Monoamine oxidase inhibitors: Seriously underused in the treatment of major depression","authors":"Tom K. Birkenhager, Willemijn T. Heijnen","doi":"10.1111/acps.13753","DOIUrl":"10.1111/acps.13753","url":null,"abstract":"<p>Monoamine oxidase inhibitors (MAOIs) were the first licensed antidepressants, they were discovered serendipitously, during a trial of iproniazid in patients with tuberculosis in the 1950s. Iproniazid appeared to have a “psychic energizing effect,” which resulted in the improvement of depressive symptoms in some tuberculosis patients,<span><sup>1</sup></span> around that time, iproniazid was shown to inhibit the MAO enzyme. Iproniazid was approved as an antidepressant, and this led to the development of several other MAOIs. Brain neurotransmitter levels are inactivated by MAO-A (serotonin, norepinephrine, dopamine) and MAO-B (dopamine) isoenzymes. Inhibition of the MAO enzyme leads to an increasing synaptic availability of these monoamines. In addition, tranylcypromine is similar in chemical structure to amphetamine and shares its dopamine-releasing and stimulant-like effects. Tranylcypromine and phenelzine are the most frequently used non-selective MAOIs, which bind the MAO enzyme irreversibly, and deactivate it permanently. Moclobemide is a selective MAO-A inhibitor, and enters into a reversible binding to the enzyme. Tranylcypromine and Phenelzine were widely prescribed until the late 1960s. The use of MAOIs has declined dramatically, as stated in their network meta-analysis by Gimenez-Palomo et al.<span><sup>2</sup></span> The historical perspective is important in understanding this decline.</p><p>In the 1960s it was not well understood that MAOIs inhibit the breakdown of tyramine, and that excessive tyramine intake when using an MAOI, can lead to a hypertensive crisis. A series of initially unexplained hypertensive crises actually occurred, some even resulting in stroke. The cause of this “cheese reaction” was uncovered in the late 1960s, but the fear for the hypertensive reaction remained. Furthermore, in one of the first large randomized clinical trials in psychiatry,<span><sup>3</sup></span> which included 260 depressed patients, both ECT and imipramine appeared to be effective, whereas phenelzine and placebo were not. In hindsight, one may well argue, that both the duration of treatment with phenelzine (4 weeks) and its dose (maximum 60 mg daily) were insufficient, therefore, phenelzine fell short of its full efficacy potential. Subsequently, MAOIs were regarded as not very effective and dangerous antidepressant drugs. This perception influenced physicians to strongly favor tricyclic antidepressants (TCAs) over MAOIs. Usage of MAOIs further declined, following the development of newer antidepressants, especially the selective serotonin reuptake inhibitors (SSRIs). Concerns about the safety profile of MAOIs, including potentially dangerous drug–drug interactions, which could result in serotonin syndrome, and the risk of a hypertensive crisis restricted their use. Furthermore, the use of MAOIs was not promoted by any pharmaceutical company.</p><p>In several countries the number of prescriptions of MAOIs is extremely low: about 500 patie","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"150 6","pages":"497-499"},"PeriodicalIF":5.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acps.13753","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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