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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision
Abstract
In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.
... The WFSBP Guidelines were last updated in 2008, followed by the development of a guideline focused on primary care providers in 2012 [11,12]. The 2008 guidelines suggest that symptom rating scales, specifically the Hamilton Anxiety Scale (HAM-A), may be useful to monitor treatment effectiveness in patients with GAD [11]. ...
... The WFSBP Guidelines were last updated in 2008, followed by the development of a guideline focused on primary care providers in 2012 [11,12]. The 2008 guidelines suggest that symptom rating scales, specifically the Hamilton Anxiety Scale (HAM-A), may be useful to monitor treatment effectiveness in patients with GAD [11]. Yet, they note that the Clinical Global Impression Scale (CGI) or self-reported outcome measures may be reasonable alternatives in busier practice settings [11]. ...
... The 2008 guidelines suggest that symptom rating scales, specifically the Hamilton Anxiety Scale (HAM-A), may be useful to monitor treatment effectiveness in patients with GAD [11]. Yet, they note that the Clinical Global Impression Scale (CGI) or self-reported outcome measures may be reasonable alternatives in busier practice settings [11]. The Anxiety Disorder Association of Canada (ADAC) guidelines also mention that objective screening process if rating scales were administered outside of inpatient and outpatient psychiatry or by another discipline, other than psychiatry. ...
... Für die in der Tabelle aufgeführten alternativen Medikamente besteht zum Teil keine ausreichende Evidenz in Form von kontrollierten Studien. Die Beschreibung der Studienlage zum Vorgehen bei Therapieresistenz findet sich bei Bandelow et al. (Bandelow et al., 2008 ...
... Offene Studien zur Behandlung von Patienten mit einer Panikstörung, die auf eine Standard-Pharmakotherapie nicht ansprachen, finden sich bei (Bandelow et al., 2008). ...
... Einige Medikament wurden in offenen Studien untersucht (Tabelle 8) (siehe auch Bandelow et al. (2008;Samuel et al., 2011). ...
... There is no study that fulfils the criteria valid for category A of empirical evidence (positive evidence from controlled studies (e.g. double-blind)) (Bandelow et al., 2008). Only a few studies respond to some criteria of category B (limited positive evidence from controlled studies), but none contained a placebo arm. ...
... Indeed, the methodologies differ widely between the studies as to previous antipsychotic medication, doses of drug B used and study duration. Moreover, there are no double-blind placebo-controlled studies which merit scoring as level A evidence (Bandelow et al., 2008). ...
Objective:
The aim of this review is to analyse the literature regarding studies centred on the clinical outcome of individuals affected by schizophrenia and treated with various antipsychotics, and then switched to orally administered partial D2-dopamine agonists (PD2A): Aripiprazole (ARI), brexpiprazole (BREX) or cariprazine (CARI).
Method:
A PubMed literature search was performed on 16 February 2021, and updated on Jan 26, 2022 for literature on antipsychotic switching in individuals affected by schizophrenia. Literature was included from 2002 onward. Six strategies were defined: Abrupt, gradual and cross-taper switch, and 3 hybrid strategies. The primary outcome was all-cause discontinuation rate per switch strategy per goal medication.
Results:
In 10 reports on switching to ARI, 21 studies with different strategies were described, but there were only 4 reports and 5 strategies on switching to BREX. Only one study about CARI was included, but it was not designed as a switch study. The studies are difficult to compare due to differences in methodology, previous antipsychotic medication, doses of the introduced P2DA and study duration.
Conclusion:
This analysis did not reveal evidence for a preferable switching strategy. A protocol should be developed which defines optimal duration, instruments to be used, and the timing of the exams.KEY MESSAGESMost switch studies on partial D2-agonists focus on ARI, with only a few on BREX, while little is known about the clinical outcome of switching individuals to CARIThere is a wide variation of possible switch methods: Abrupt switch - gradual switch - cross-tapering switch - hybrid strategies including plateau switchThe protocols used differ considerably between the studies. A strict comparison between the studies is difficult, for which reason the present evidence does not support an unambiguous preference for a particular switch strategy.From a methodological point of view, a standardised clinical protocol should be developed to allow comparisons between studies regarding the clinical outcome of individuals switched from one antipsychotic drug to another.
... Em relação ao tratamento, as principais alternativas são as farmacológicas, e constitui-se um consenso que os inibidores da recaptação da serotonina seriam o padrão-ouro no tratamento do TOC (Bandelow et al., 2008;Fineberg et al., 2013); e a terapia cognitivo comportamental (TCC), principalmente as técnicas de exposição e prevenção de resposta (Ponniah, Magiati & Hollon, 2013 Khalsa & Beckett, 1996), onde foram apresentados alguns resultados encorajadores. ...
A definição do Transtorno Obsessivo-Compulsivo (TOC) indica um espectro que se caracteriza por pensamentos obsessivos (obsessões) e por comportamentos repetitivos ou atos mentais (compulsões). As principais alternativas de tratamento são as farmacológicas e as psicoterápicas, no entanto, estima-se que aproximadamente 40 a 60% dos pacientes não atinjam alívio satisfatório dos sintomas. Desta forma, apresentamos o Kundalini Yoga, como um tratamento complementar. Foram realizadas 36 sessões com um protocolo de técnicas “específicas para o TOC”. Foram utilizados para avaliação os seguintes instrumentos: as Escalas Obsessivo-Compulsivo (YBOCS) e dimensional (DYBOCS), os inventários Beck de Ansiedade (BAI), e o Teste de Qualidade de Vida da OMS (WHOQOL). Nesta pesquisa com 24 pacientes adultos, houve uma melhora significativa (46%) na gravidade do TOC, especialmente nos sintomas de conteúdo sexual/religioso (54%) e de contaminação (33%). Também melhoraram em quase 48% os sintomas de ansiedade e todos os aspectos da qualidade de vida (física 9,7%, psicológica 11,7%, social 12,6% e ambiental 4,8%). O Kundalini Yoga se mostrou uma ferramenta efetiva para aliviar os sintomas do TOC em algumas dimensões, reduzir a ansiedade e melhorar a qualidade de vida.
... Em relação ao tratamento, as principais alternativas são as farmacológicas, e constitui-se um consenso que os inibidores da recaptação da serotonina seriam o padrão-ouro no tratamento do TOC (Bandelow et al., 2008;Fineberg et al., 2013); e a terapia cognitivo comportamental (TCC), principalmente as técnicas de exposição e prevenção de resposta (Ponniah, Magiati & Hollon, 2013 Khalsa & Beckett, 1996), onde foram apresentados alguns resultados encorajadores. ...
... Chronic anxiety without treatments may lead to suicidal thoughts. The two methods to treat anxiety disorder properly were psychopharmacological drugs and psychological therapy (Bandelow et al., 2008;National Institute for Health and Clinical Excellence (NICE), 2011; Baldwin et al., 2014). ...
The search and development of new therapeutic agents from medicinal plants to alleviate anxiety is well justified due to the increasing cases of anxiety disorder and lack of effective treatment. Moringa oleifera has been used traditionally to treat anxiety. However, there is still lack of understanding on the mechanism for its anxiolytic effect. The purpose of this study was to investigate the anxiolytic effects and the mechanism of ethanolic extracts of the leaves of M. oleifera (MOLE) by observing behavioural changes of the Danio rerio and the differential gene expression analysis using custom RT2 Profiler PCR array. A 14-day chronic behaviour study was conducted using three concentrations of MOLE (500 mg/L, 1000 mg/L and 2000 mg/L) fluoxetine as the positive control. Stress-induced D. rerio treated with 1000 mg/L MOLE showed the lowest level of anxiety compared to other groups as evidenced by a decrease in freezing episodes and freezing time, increased entries into the light region. The fish also showed significant changes in the expression of crhb, faah2a, mao, and pah genes. MOLE with the presence of quercetin and kaempferol are believed to exert its anxiolytic effects through differential expression of gene (i) modulating the function of GABAA receptor (crhb), (ii) inhibiting the expression of nitric oxide synthase (NOS) and the production of nitric oxide, (iii) increasing the AEA levels in the brain (faah2a), (iv) increasing the level of dopamine levels in the brain (mao). These findings provide valuable insights into the potential use of MOLE as a treatment for anxiety-related disorders as well as the significance of the molecular pathways involved in its anxiolytic properties.
... Thus far, different medications have been used in augmentation with SSRIs in the treatment of OCD. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines have stated that augmentation of the antipsychotics risperidone, haloperidol, olanzapine, or quetiapine with an SSRI is more effective than monotherapy with SSRIs [13]. Other atypical antipsychotics, such as aripiprazole [14], may also be bene cial. ...
Background: obsessive–compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs.
Objectives: In this systematic review and meta-analysis, we assessed the efficacy of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD.
Methods: We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients.
Results: We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z=8.37, P<0.00001), in the compulsion subgroup (Z=5.22, P<0.00001), and in the obsession subgroup (Z=8.33, P<0.00001). They are well-tolerated, and have mild side effects and do not result in withdrawal.
Conclusion: Augmentation of 5HT-3 antagonists with SSRIs can be beneficial in treating moderate to severe OCD. Further multi-center trials under adequate conditions in longer periods are needed to help come up with a comprehensive action plan.
... Относительно возможной фармакологической профилактики ПТСР кокрейновский анализ говорит о том, что на сегодняшний день нет препаратов, которые могут быть рекомендованы для профилактики ПТСР у лиц как с симптомами психологического дистресса, так и без него после переживания серьезного травматического со бытия [71][72][73][74][75]. ...
PTSD was determined as a stand-alone disorder about 50 years ago, and since then it is considered to be in the focus of attention of the mental health specialists. It’s main clinical features are the set of symptoms of re-experience of the traumatic event in here and now situation. They are defined to be the core symptoms for PTSD diagnostic. Clinical features and disorder course are the subject of wide prospective cohort studies with the use of the standardized psychometric instruments since the 80-s of the last century. In the new ICD-11 mental disorders classification, stress-associated disorders are defined as stand-alone rubric, the core PTSD symptoms are defined, the complex PTSD is proposed as a new diagnosis for the coding of persistent caused by prolonged psychotraumatic experience personality changes, the life-threatening diagnosis and intensive care unit experience were added to the list of PTSD triggers. The PTSD diagnosis is considered to be a challenging clinical task. The connection between symptoms manifestation and extreme traumatic experience should be established, one should take into consideration the existence of possible usually several weeks before symptoms manifestation latent period. It is useful to implement the recommended diagnostic instrument for the diagnosis verification and symptoms dynamic evaluation. The combination of pharmacotherapy and psychotherapy is recommended for PTSD treatment, individual approach should be used in case-management. In 2022 WFSBP Task Force on Treatment Guidelines for Anxiety, O and Post-Traumatic Stress Disorders have been published, there for the first-time cognitive behavior psychotherapy was determined as highly evidence based PTSD psychotherapeutic method of treatment. In March 2023 ministry of health of the Russian Federation has approved national PTSD clinical guidelines, where recommended medication list has been proposed taking into account the national clinical experience, in particular it includes a wide range of non-benzodiazepine anxiolytics. The article emphasizes the opportunities of their use and presents a clinical vignette where etifoxine is proposed as treatment of choice.
... As diretrizes internacionais recomendam para o tratamento da TAG os inibidores seletivos da recaptação da serotonina (ISRSs), inibidores da recaptação da serotonina e noradrenalina (IRSNs) e pregabalina como medicamentos de primeira linha no manejo, por terem uma eficácia bem estabelecida e adequados perfis de segurança, ficando para segunda linha de tratamento os benzodiazepínicos como diazepam. No entanto, sabe-se que os efeitos colaterais das medicações descritas como náuseas e disfunção sexual em decorrência dos ISRSs e IRSNs e tontura e sedação gerados pela pregabalina acabam se tornando motivos para descontinuação do tratamento e insuficiência no resultado terapêutico desejável (BANDELOW et al., 2008;BUOLI et al., 2013;ROBERGE et al., 2015). ...
O transtorno de ansiedade generalizada (TAG) é caracterizado por um distúrbio com características de ansiedade e preocupação excessivas, além de sintomas associados, sendo um dos transtornos de ansiedade mais prevalentes, com uma prevalência mundial estimada em torno de 6%. O presente estudo de revisão buscou avaliar novas evidências na abordagem terapêutica do transtorno de ansiedade generalizada, documentadas por meio de estudos clínicos e randomizados. Trata-se de uma pesquisa de revisão integrativa realizada por meio da base de dados PubMed, que levou em consideração os seguintes critérios de inclusão: ensaios clínicos e testes controlados e randomizados; artigos publicados no último ano; que possuíam texto completo disponível e que abordassem acerca de novas evidências no manejo do transtorno de ansiedade generalizada. Ficou constatado que a terapia de coloração pode trazer alívio nos sintomas de ansiedade e melhorias no humor positivo, reduzindo o humor negativo, o que eleva ainda mais os efeitos do tratamento dos pacientes com TAG. Além disso, a terapia comportamental dialética proporcionou uma melhora na função executiva dos pacientes com TAG, sendo uma medida eficaz na melhora de transtornos mentais e com boa capacidade para reduzir a gravidade de tais transtornos mentais. Outro ponto constatado é acerca do uso da tandospirona, em que o uso das doses de 60 mg/dia ou 30 mg/dia de tandospirona demonstraram eficácia promissora em pacientes com TAG. Por fim, foi visto que a doxepina em baixas doses possui boa eficácia terapêutica e tolerabilidade, fazendo-se um medicamento útil e racional para o manejo de tais pacientes.
... Three studies investigating the efficacy of CBT alone or combined CBT and pharmacotherapy found that compared to combined treatment, CBT alone produced superior results, with the studies indicating that the effects of CBT were found to be durable and long-lasting post-treatment (2,155,(159)(160)(161). Upon treatment discontinuation, combined treatment of CBT and pharmacotherapy has been associated to greater rates of relapse (162). ...
The current narrative review summarizes and examines several theories of panic disorder (PD) including biological theories, encompassing neurochemical factors, metabolic and genetic theories, respiratory and hyperventilation theories and cognitive theory. Biological theories have informed the development of psychopharmacological treatments; however, they may be limited in their utility given the efficacy of psychological treatments. In particular, behavioral and, more recently, cognitive models have garnered support due to the efficacy of cognitive-behavior therapy (CBT) in treating PD. The role of combination treatments has been found to be superior in the treatment of PD in particular cases, lending support for the need for an integrated approach and model for PD given that the etiology of PD is complex and multifactorial.
... From the perspective of treatment, many studies showed that, besides medication, Cognitive-Behavioral Therapy (CBT) constitutes one of the most efficient psychological interventions for GAD (Dugas et al., 2010;Cuijpers et al., 2014). In this regard, both forms of treatment are considered effective (Bandelow et al., 2008), and the antidepressant and/or anxiolytic medication can be successfully augmented with different CBT orientations (Veale and Stout, 2010;Orvati Aziz et al., 2020). According to the existing empirical evidence, CBT approaches are flexible and highly adaptable psychological interventions that knew a rapid development towards an integrative orientation that, beyond the traditional delivery, also embraced digital, Internet-based and VR-augmented programs (Lindner, 2021). ...
Introduction
Generalized Anxiety Disorder (GAD) is a prevalent emotional disorder associated with increased dysfunctionality, which has a lasting impact on the individual’s quality of life. Besides medication, Cognitive-Behavioral Therapy (CBT) represents the golden standard psychotherapeutic approach for GAD, integrating multilevel techniques and various delivery formats that enable the development of tailored treatment protocols. The objective of this study was to compare the efficiency of a standard CBT protocol targeting worries, dysfunctional beliefs, and intolerance of uncertainty with an integrative and multimodal CBT intervention augmented with Virtual Reality (VR).
Materials and methods
This study included 66 participants (Mage = 22.53 years; SD = 2.21) with moderate GAD symptoms that were randomized to the standard CBT group (CBTs; N = 32) and the Integrative and Multimodal CBT augmented with VR (IM-VRCBT; N = 34) group. The interventions comprised 10 weekly sessions conducted by trained CBT therapists, including cognitive restructuring, problem-solving, behavioral exposure, and relaxation techniques. Baseline and post-assessments were conducted with both groups. Primary outcome measures included the Hamilton Anxiety Rating Scale (HARS) and Penn-State Worry Questionnaire (PSWQ) to evaluate the severity of GAD symptoms and worries, respectively. Secondary outcomes involved the administration of Automatic Thoughts Questionnaire (ATQ), Dysfunctional Attitudes Scale (DAS) and Unconditional Self-Acceptance Questionnaire (USAQ).
Results
Both interventions determined statistically significant effects on both primary and secondary outcomes (ps < 0.001) in the expected direction. However, CBTs was associated with higher effect sizes for anxiety (Cohen’s d = 2.76) and worries (Cohen’s d = 1.85), in contrast to IM-VRCBT. Also, secondary analyses revealed positive correlations between changes in anxiety and worries level and the reduction of dysfunctional cognitive processes.
Conclusion
This research emphasized the effectiveness of CBT interventions for treating adults with moderate GAD symptomatology. Specifically, both interventions were efficient for reducing anxiety symptomatology present at individuals with GAD. However, regarding cognitive dysfunctions like worries, the standard CBT protocol performed better, as compared to the IM-VRCBT. In addition, we conclude that VR could be integrated within CBT interventions in a single protocol for GAD treatment.
Introduction
Obsessive‐compulsive disorder (OCD) is marked by a high rate of treatment resistance. Patients are often left trialing medications within multiple drug classes with little response, causing heterogeneity to emerge in prescribing patterns. This analysis seeks to investigate the selection and dosing of the pharmacotherapy utilized, to portray an overview of prescribing trends in the United States.
Methods
This retrospective, single center, review of electronic medical records investigated the pharmacotherapy utilization of patients with a primary diagnosis of OCD. Two hundred and ninety‐five patients who received OCD treatment at an urban, academic medical center were included in the study. Patients were included in the review if they were at least eighteen years of age and were assigned a diagnosis of OCD according to DSM‐5 criteria.
Results
Psychotropic pharmacotherapy was integrated into the care of 93% of patients. Selective serotonin reuptake inhibitors were the most utilized medication class at 85% followed by benzodiazepines (47%) and second‐generation antipsychotics (37%). Tricyclic antidepressants and first‐generation antipsychotics were the two medication classes utilized the least at 13% and 2% respectively. Additionally, mood stabilizers and serotonin‐norepinephrine reuptake inhibitors were utilized at rates of 8% and 16%, respectively.
Conclusions
Evidence‐based treatment guidelines are being followed with varying augmentation strategies widely prevalent, thus displaying the heterogeneity in treating OCD. A high rate of benzodiazepine utilization highlights a practice trend with potential ties to clinical factors, such as the latency to treatment effect of other first‐line pharmacotherapies. Future prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that contribute to the variation in prescribing practices and whether these variations influence treatment outcomes.
Introduction
Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta‐analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management.
Methods
We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason).
Results
We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high‐frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD‐related symptoms, including depression and anxiety symptoms, and overall PTSD severity.
Conclusions
This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD‐related symptoms.
Trial registration: PROSPERO CRD42023391562.
Obsessive‐compulsive disorder (OCD) is a chronic disease with a prevalence in the general population of around 2%–3%, generally accompanied by a severe impairment of functioning and quality of life. A consistent subgroup of patients may not achieve adequate symptom remission with first‐line treatments (i.e., cognitive behavioral therapy, selective serotonin reuptake inhibitors [SSRIs]). The most validated option for treatment‐resistant cases relies on the augmentative use of antipsychotics to SSRIs, preferably of the ‘second generation’. Indeed, dopamine appears to be crucially involved in OCD neuropathology due to its implication in systems relating to goal‐directed behaviour and maladaptive habits. Nevertheless, the mechanism of action of antipsychotics in OCD symptom improvement is still unclear. Risperidone, aripiprazole, and haloperidol seem to be the most useful medications, whereas ‘first generation’ antipsychotics may be indicated in case of comorbidity with tics and/or Tourette Syndrome. Antipsychotic augmentation may be also related to side‐effects, particularly in the long term (e.g., alteration in metabolic profile, sedation, extrapyramidal symptoms). The present mini‐review sought to provide the most updated evidence on augmentative antipsychotic use in treatment‐resistant patients with OCD, providing a road map for clinicians in daily practice and shedding light on avenues for further research.
Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment‐resistant anxiety disorders (TR‐AD) informing such trials is currently lacking. We used a Delphi method‐based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR‐AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free‐text responses to a 29‐item questionnaire on relevant aspects of TR‐AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR‐AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR‐AD vs. “difficult‐to‐treat” anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method‐based consensus on operational criteria for TR‐AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence‐based stepped‐care treatment algorithms for patients with anxiety disorders.
Обоснование: в развитии панического расстройства играет роль накопление гормонов стресса - кортизола и пролактина, а также циклические изменения уровня эстрогена.Цель: представить обзор доказательных исследований нейроэндокринных основ патогенеза панического расстройства, доступ к которым получен через базы данных Pubmed и Medline.Результаты: рассмотрены современные взгляды на терапию панического расстройства, в частности на оценку эффективности различных групп антидепрессантов. Приведены данные литературы о возможных нейроэндокринологических и метаболических нарушениях, сопряженных с применением антидепрессантов различного механизма действия. По результатам анализа публикаций показано, что практически все антидепрессанты влияют на уровень пролактина, тиреоидных гормонов, гормонов ГГА-оси и существенно увеличивают риск развития метаболического синдрома и сахарного диабета 2-го типа.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-Hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs. In this systematic review and meta-analysis, we assessed the efficacy and safety of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD. We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients. We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z = 8.37, P < 0.00001), in the compulsion subgroup (Z = 5.22, P < 0.00001), and in the obsession subgroup (Z = 8.33, P < 0.00001). They are well-tolerated, and have OPEN
Mounting evidence suggests safety and tolerability of cannabis-derived and psychedelic drugs as potential novel therapeutics for psychiatric, as well as sleep and pain disorders. Evidence concerning the therapeutic efficacy of these compounds remains controversial, although some promising preliminary results are available for them in specific disorders. For example, CBD is approved as medication for treatment-refractory epilepsy, while MDMA and psilocybin are being tested in phase 3 clinical trials respectively for treatment-refractory PTSD and MDD. Despite encouraging preliminary results, further preclinical and clinical trials are required to validate these findings. Most importantly, more systematic research is required to assess the potential long-term side effects that might arise following the use of cannabinoids and psychedelic compounds in psychiatric settings.
Post-traumatic stress disorder (PTSD) is a mental disorder that develops as a result of a powerful psycho-traumatic effect of a threatening or catastrophic nature, accompanied by extreme stress, the main clinical manifestations are repeated experiences of elements of a traumatic event in a “here and now” situation in the form of flashbacks, recurring dreams and nightmares, which accompanied more often by anxiety and panic, but possibly also by anger, anger, feelings of guilt or hopelessness, a desire to avoid internal and external stimuli that resemble or are associated with the stressor. PTSD tends to form personality disorders, and is also characterized by a high prevalence of comorbid pathology. Recently, data have been accumulated on changes in the brain neurotransmitter systems and neuroendocrine disorders in patients with PTSD, as well as on the presence of morpho-functional, neuroinflammatory, and other neurobiological features. Improvement of existing and development of new pharmacotherapy algorithms is an important component of care provided to patients with PTSD. Despite the leading role of psychotherapy in the treatment of this disorder, prevention of chronicity and relapses, in order to achieve a quick effect and form patients' adherence to treatment, within the framework of a personalized approach, the use of psychopharmacotherapy is recommended, the effectiveness of which should be evaluated during the entire course of therapy.
Obsessive-compulsive disorder (OCD) is one of the most debilitating mental health conditions, interrupting functioning at school and social well-being in children and adolescents. Youth tend to delay interventions and when sought, response to treatment might not be optimal. The current article discusses treatment guidelines for youth with OCD and pediatric autoimmune neuropsychiatric symptoms. [Journal of Psychosocial Nursing and Mental Health Services, 61(8), 11-15.].
Lamotrigine and aripiprazole have shown efficacy as augmentation agents of serotonin reuptake inhibitors for treatment resistant obsessive-compulsive disorder (OCD). To date, the efficacy of lamotrigine/aripiprazole augmentation has not been reported in OCD treatment. Herein, we report the case of a 37-year-old male with severe OCD and comorbid depression whose symptoms markedly improved after low-dose lamotrigine/aripiprazole augmentation to clomipramine. Our report suggests that early glutamatergic/antipsychotic augmentation contributes to rapid remission of OCD symptoms.
Objectives:
Obsessive-Compulsive Disorder (OCD) has been considered to be a chronic illness; however, some authors described a subtype of OCD characterised by symptom-free periods of time: Episodic-OCD (E-OCD). Only few studies focussed on this subtype of the disorder. The objectives of this research were to study the association between the episodic course of the disorder and lifetime psychiatric comorbidities and to investigate socio-demographic and other clinical features correlated to the episodic course.
Methods:
The sample is composed of adult OCD patients. The course was defined episodic when at least one circumscribed symptom-free interval of at least 6 months was present. The sample was divided into two subgroups: Episodic-OCD and Chronic-OCD. Differences between groups were analysed with Student's t-test, χ2 tests, Fisher test and multivariate logistic regression.
Results:
Data regarding 585 individuals were collected. 14.2% (N = 83) of our sample had an episodic course. Bipolar I comorbid disorder, abrupt onset, lower severity of illness and lower rates of repeating compulsions were associated with the likelihood of having an E-OCD.
Conclusions:
Our findings confirm that a significant proportion of OCD patients have an episodic course and that E-OCD could represent a specific endophenotype.
Anxiety disorders are the most prevalent mental health issues worldwide and can have significant detrimental effects on people's quality of life and daily functioning. Nurses in a range of healthcare settings are likely to encounter people with various anxiety disorders, so it is essential that they have adequate knowledge and understanding of these conditions. This article explores the development of anxiety, before outlining the aetiologies and symptoms of common anxiety disorders. The author also provides an overview of some of the treatments available for anxiety disorders and explains the nurse's role in supporting those affected by these conditions.
Anxiety disorders are among the most common mental health conditions affecting pediatric populations. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, recommends objective measurement of pediatric anxiety for evaluation of symptomatology and treatment response. The objective of the current review was to summarize recommendations and resources for measuring pediatric anxiety, and to quantify and characterize use of outcome measures for generalized anxiety in pediatric psychiatry. These findings represent an essential step toward understanding how and to what extent anxiety rating scales are used in pediatric psychiatry and where quality improvement initiatives may be needed. Education, training, and further research are warranted to optimize use of measurement-based care for generalized anxiety in pediatric psychiatry settings and to determine which scales are optimal for use in this context. [Journal of Psychosocial Nursing and Mental Health Services, 61(5), 11-16.].
Purpose of Review: To provide an update of the current evidence of cardiac disease–induced posttraumatic stress disorder (CDI-PTSD) with a focus on acute coronary events.
Recent Findings: A cardiovascular disease, particularly a life-threatening cardiac event is often a highly stressful experience that can induce PTSD in patients and their caregivers, taking a chronic course if left untreated. There are several features
distinguishing CDI-PTSD from “traditional” PTSD induced by external trauma, namely enduring somatic threat, inability to avoid trauma-related cues and hyperarousal with internal body sensations leading to constant fear of recurrent cardiac events. An increased risk of recurrent CVD events may be explained by pathophysiological changes, an unhealthy lifestyle and non-adherence to cardiac treatment. A trauma-focused approach might be useful to treat CDI-PTSD.
Summary: Treatment options for patients and caregivers as well as long-term effects of trauma-focused interventions on physical and mental health outcomes should be future research directio
Post-traumatic stress disorder (PTSD) is a mental disorder that develops as a result of a powerful psycho-traumatic effect of a threatening or catastrophic nature, accompanied by extreme stress, the main clinical manifestations are repeated experiences of elements of a traumatic event in a “here and now” situation in the form of flashbacks, recurring dreams and nightmares, which accompanied more often by anxiety and panic, but possibly also by anger, anger, feelings of guilt or hopelessness, a desire to avoid internal and external stimuli that resemble or are associated with the stressor. PTSD tends to form personality disorders, is characterized by a high prevalence of comorbidity and severe social consequences. Improving diagnostic algorithms is an important component of care provided to patients with PTSD due to the need for accurate differentiation and verification of disorders, as well as the development and improvement of personalized methods of therapy. Based on a review of domestic and foreign literature, the article highlights topical issues of PTSD classification, provides a diagnostic algorithm in the context of an interdisciplinary approach. The importance and complexity of a personalized examination are noted, the main stages, methods and diagnostic tools necessary for the clinical verification of PTSD are considered. The necessity of involving medical psychologists in professional teams to participate in the implementation of treatment and diagnostic measures in order to determine the individual psychological characteristics of the patient that are preserved and impaired due to the disease, to identify targets for psychotherapeutic effects, and to objectify the dynamics of therapeutic measures, is considered.
Objective:
Obsessive thoughts and compulsive behavior and their related disorder Obsessive-Compulsive Disorder (OCD) commonly occur in the general population. Clinical populations indicate a high level of stability, although there are few longitudinal studies in the general population. The recommended drug treatments are SSRIs/TCAs. However, there are few long-term follow up studies. The goal of this study was to 1) examine the occurrence and stability of obsessions, compulsions, and OCD in a longitudinal population-based survey, 2) investigate the use of SSRI and TCA and the potential effect on symptoms.
Methods:
A ten-year longitudinal general population in Stockholm was used (2000 and 2010, n = 5650) Obsessional washing, checking, intrusive unpleasant thoughts and the level of suffering due to these symptoms were measured by self-report. Information on use of SSRIs and TCAs by these individuals was obtained from registers. Stability was examined using contingency tables and multinomial logistic regression.
Results:
At baseline, 2.1, 11.7 and 11.9% reported obsessional washing, checking and intrusive thoughts. A total of 5% reported considerable suffering from these (i.e. OCD). Based on psychiatric interview only 0.4% had OCD. Ten years later a quarter of OCD cases were still classified as having OCD, one quarter reported any obsessive or compulsive symptom and half were classified as symptom-free. Treatment receipt was low and controlling for medication did not change the stability.
Conclusion:
Obsessive thoughts and compulsive behavior are common and stable. While this group is potentially undertreated, there is no indication that those treated display a different pattern of recovery.
Obsessive-compulsive disorder (OCD) affects 1–2% of children and is associated with functional impairment and diminished quality of life. Several treatments are efficacious: cognitive behavioral therapy (CBT) with exposure and response prevention, serotonin reuptake inhibitor (SRI) monotherapy, and combined treatment (SRI + CBT). Expert clinician-informed practice parameters suggest that youth with mild to moderate OCD should be treated initially with CBT yet SRIs are frequently employed as the first-line intervention or in combination with psychotherapy in applied practice. Empirical data to guide SRI discontinuation in pediatric OCD are very limited. This study, Promoting OCD Wellness and Resiliency (POWER), aims to address this gap through a two phase, double-blinded, placebo-controlled, randomized controlled non-inferiority trial with the purpose of evaluating whether youth with OCD on an SRI can discontinue their medication after successful CBT augmentation and maintain wellness for a period of 24 weeks during which they receive maintenance CBT that models standard-of-care. In this paper we describe the rationale and methodological design of the POWER study.
Pharmacological treatment is a mainstay of the care of individuals with obsessive-compulsive disorder. Robust evidence supports the use of the selective serotonin reuptake inhibitors and the older tricyclic drug clomipramine. Other antidepressants are less effective (or have been insufficiently studied). When first-line treatment with these agents, and with appropriate psychotherapy, is ineffective, several augmentation strategies are available, though their evidentiary support is weaker. A substantial minority of patients have persistent symptoms despite optimal evidence-based treatment. Further work and more treatment options are needed.
This volume presents up-to-date, comprehensive and high quality reviews of the psychopharmacological evidence-base for each of the major psychiatric disorders, written by expert psychopharmacologists from around the world. Building on the success of the first edition, the volume summarizes the wealth of new developments in the field and sets them within the context of day-to-day clinical practice. All chapters have been fully updated and new contributions on personality disorders and substance dependence added. Each chapter provides information about optimal first line pharmacological interventions, maintenance pharmacotherapy and the management of treatment-refractory patients. The content is organized according to the DSM-V listing of psychiatric disorders, and covers all major conditions including schizophrenia, mood disorders, anxiety disorders, eating disorders and Alzheimer's disorder. These issues lie at the heart of clinical psychopharmacology, making this book invaluable to all practising and trainee clinicians, in a mental health setting or a less specialised environment.
The use of anxiolytic medications requires a careful assessment of the risk for misuse, dependence, and withdrawal. Clinicians should be aware of the range of presentations for misuse and dependence, which includes non-medical use, diversion, self-medication, inappropriate prescription, and behavioral and psychological syndromes of addictive disorders. In comparison to other anxiolytics, benzodiazepines pose the greatest risks for misuse, dependence, and withdrawal. A strong association between benzodiazepine misuse with other sedating drugs such as opioids has been reported and is associated with increased overdose deaths. Careful monitoring is needed for benzodiazepine withdrawal, which can be severe, and gradual tapers with psychological support should be offered. Cognitive behavioral therapy has evidence for efficacy through the stages of benzodiazepine discontinuation and relapse prevention. Although reports of gabapentinoid misuse, dependence, and withdrawal have been increasing in the literature over the years, the numbers involved are small relative to the large number of individuals who have been exposed to the drugs, and true population-based prevalence rates remain poorly characterized. However, randomized controlled trials involving discontinuation in people with anxiety disorders do not show evidence for any significant withdrawal potential. Azapirone anxiolytics including buspirone and tandospirone likely have negligible pharmacological potential for misuse, dependence, and withdrawal. While there may be a gradient of risk for misuse and dependence from benzodiazepines, having the highest, through gabapentinoids to azapirones, having the least, the greatest risk factor by far with all anxiolytic drug classes is the presence of other substance use disorders. This suggests that the pre-existing characteristics of individuals using a medication may contribute as much if not more than the pharmacology of specific drugs in determining the likelihood of misuse and dependence.
Cognitive-behavioral therapy, including exposure therapy, as well as certain psychopharmacotherapies are considered effective first-line treatments for anxiety disorders. However, not all patients respond sufficiently to these treatment options. D-4-amino-3-isoxazolidone, commonly known as D-cycloserine, is an antibiotic that has been increasingly studied for its effects as a partial agonist of the N-methyl-D-aspartate receptor, a receptor in the brain that is thought to be relevant for synaptic plasticity. Experimental studies in animals indicate that D-cycloserine may enhance learning and memory processes. As learning represents a central goal of many psychotherapy methods, the supposed effect of D-cycloserine on learning may be utilized to improve psychotherapy outcomes. In recent years, a growing body of evidence from randomized controlled trials suggests that small doses of D-cycloserine may be used to augment exposure therapy for anxiety disorders, increasing the efficacy of exposure therapy by a small-to-moderate amount. The size of this augmentation effect appears to depend on moderating factors such as the number of D-cycloserine doses, timing of administration, or the patient’s severity of illness. Additional randomized controlled trials are needed to identify optimal administration procedures for enhancing exposure therapy outcomes in both adults and children. Further studies assessing the usefulness of D-cycloserine in the treatment of other mental disorders as well as its possible effects on the outcome of other psychotherapeutic methods would also be desirable.
OCD is characterized by obsessions and compulsions that cause distress, are time-consuming, and interfere with a patient's social, occupational, or other areas of functioning. SSRIs are first-line pharmacologic treatment options and produce response rates of up to 60% in patients with OCD. Several potential strategies have been evaluated for enhancing patient response, including high-dose SSRI therapy, antipsychotic augmentation, and memantine augmentation. Three patient cases are used to explore treatment guidelines, evaluate existing literature, and provide pharmacotherapy recommendations for the management of patients with OCD when first-line therapy fails.
This volume presents up-to-date, comprehensive and high quality reviews of the psychopharmacological evidence-base for each of the major psychiatric disorders, written by expert psychopharmacologists from around the world. Building on the success of the first edition, the volume summarizes the wealth of new developments in the field and sets them within the context of day-to-day clinical practice. All chapters have been fully updated and new contributions on personality disorders and substance dependence added. Each chapter provides information about optimal first line pharmacological interventions, maintenance pharmacotherapy and the management of treatment-refractory patients. The content is organized according to the DSM-V listing of psychiatric disorders, and covers all major conditions including schizophrenia, mood disorders, anxiety disorders, eating disorders and Alzheimer's disorder. These issues lie at the heart of clinical psychopharmacology, making this book invaluable to all practising and trainee clinicians, in a mental health setting or a less specialised environment.
Serotonin reuptake inhibitor (SRI) medications are well established as first-line pharmacotherapeutic treatment for Obsessive-Compulsive Disorder (OCD). However, despite the excellent safety profile and demonstrated efficacy of these medications, a substantial proportion of individuals with OCD fail to attain sufficient benefit from SRIs.
In this narrative review, we discuss clinical features of OCD that have been associated with poorer response to SRIs, and we present pharmacotherapeutic interventions that have been explored as augmenting or alternative treatments for treatment-resistant OCD. We additionally highlight non-SRI interventions for OCD that are currently under investigation.
Pharmacotherapeutic interventions were identified via expert consensus. To assess the evidence base for individual pharmacotherapies, targeted searches for relevant English-language publications were performed on standard biomedical research databases, including MEDLINE. Information relevant to ongoing registered clinical trials in OCD was obtained by search of ClinicalTrials.gov. Pharmacotherapies are grouped for review in accordance with the general principles of Neuroscience-based Nomenclature (NbN).
Clinical features of OCD that may suggest poorer response to SRI treatment include early age of onset, severity of illness, duration of untreated illness, and the presence of symmetry/ordering or hoarding-related symptoms. Based on evolving pathophysiologic models of OCD, diverse agents engaging serotonin, dopamine, norepinephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy.
Medications with dopamine antagonist activity remain the most robustly evidence-based of augmenting interventions, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Interventions targeting glutamatergic and anti-inflammatory pathways are less well evidenced, but may offer more favorable benefit to risk profiles. Ongoing research should explore whether specific interventions may benefit individuals with particular features of treatment-resistant OCD.
The article presents the evolution of the post-traumatic stress disorder (PTSD) definition from various war syndromes to PTSD definition as a sovereign disorder and complex PTSD appearance in ICD-11 as distinct diagnosis. It is focused on the epidemiology, gender issues, clinical features and differential diagnostic PTSD aspects. It is considered elaboration of the new international clinical guidelines for the anxiety disorders including PTSD, the new pharmaceutical and psychotherapeutic treatment algorithms for PTSD based on the evidence based research data is presented. Additionally as an illustration case vignette is described.
Improving the quality of life in developed countries has contributed to an increase in its duration, which has led to an increase in the number of reported cases of Alzheimer's disease (AD) and Parkinson's disease (PD) in the world. Today, there are 26.6 million patients with AD in the world and it is suspected that by 2050 the number of such patients may increase four times. Additionally, PD in different countries is recorded among people above 60-65 years old at a level of 167 to 5703 per 100.000 population. The latest studies have made it possible to formulate the main mechanisms of the «microbiota-gut-brain» axis associated with the pathogenesis of some neurodegenerative diseases. In this review, we summarize the currently available information on the possible role of the gut microbiota in the AD and PD development. It was shown that oxidative stress is one of the main pathogenetic mechanisms of the development of neurodegenerative diseases. In addition, the deposition of lipopolysaccharides of gram-negative bacteria and amyloid of microbial origin in the brain tissue of patients with impaired permeability of the intestinal barrier plays an important role in AD. In PD, the synthesis of α-synuclein produced by bacteria and neuroinflammation are of the greatest importance. Knowledge of these mechanisms will allow the development of psychobiotics, which will reduce the risk of neurodegeneration in AD and PD.
Anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, social anxiety disorder, and others) are the most prevalent psychiatric disorders, and are associated with a high burden of illness. Anxiety disorders are often underrecognized and undertreated in primary care. Treatment is indicated when a patient shows marked distress or suffers from complications resulting from the disorder. The treatment recommendations given in this article are based on guidelines, meta-analyses, and systematic reviews of randomized controlled studies. Anxiety disorders should be treated with psychological therapy, pharmacotherapy, or a combination of both. Cognitive behavioral therapy can be regarded as the psychotherapy with the highest level of evidence. First-line drugs are the selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Benzodiazepines are not recommended for routine use. Other treatment options include pregabalin, tricyclic antidepressants, buspirone, moclobemide, and others. After remission, medications should be continued for 6 to 12 months. When developing a treatment plan, efficacy, adverse effects, interactions, costs, and the preference of the patient should be considered.
Generalized anxiety disorder (GAD) is a prevalent and highly disabling mental health condition; however, there is still much to learn with regard to pertinent biomarkers, as well as diagnosis, made more difficult by the marked and common overlap of GAD with affective and anxiety disorders. Recently, intensive research efforts have focused on GAD, applying neuroimaging, genetic, and blood-based approaches toward discovery of pathogenetic and treatment-related biomarkers. In this paper, we review the large amount of available data, and we focus in particular on evidence from neuroimaging, genetic, and neurochemical measurements in GAD in order to better understand potential biomarkers involved in its etiology and treatment. Overall, the majority of these studies have produced results that are solitary findings, sometimes inconsistent and not clearly replicable. For these reasons, they have not yet been translated into clinical practice. Therefore, further research efforts are needed to distinguish GAD from other mental disorders and to provide new biological insights into its pathogenesis and treatment.
Objectives
Several international guidelines for the pharmacological treatment of posttraumatic stress disorder (PTSD) have been published. However, it is unclear whether clinicians use these procedures in their daily practice. We compared the psychopharmacological prescription patterns in a Swiss adult psychiatric center with international clinical guidelines at admission and discharge.
Methods
Retrospective chart review study between 2005 and 2015 of adult patients with PTSD and no other documented psychiatric comorbidity.
Results
Fifty-two outpatients and 21 inpatients were included; 47% had at least one psychopharmacological treatment at admission. Among them, 47% had one or several antidepressants, mainly escitalopram (31%, n = 5) or citalopram. At discharge, 68% had at least one psychopharmacological treatment. Among them, 76% had at least one antidepressant, mainly escitalopram (34%, n = 13) or mirtazapine (21%, n = 8). They were compared to the guidelines of the Department of Veterans Affairs and Department of Defense (VA/DoD), showing 19% of the patients treated with antidepressants at admission were in agreement with the guidelines (sertraline, fluoxetine, paroxetine, venlafaxine), and 26% at discharge. In addition, we found prescriptions of benzodiazepines (62% at admission and 50% at discharge), antipsychotics (12% and 22%), Z-drugs (zolpidem, zopiclone: 15 and 40%) and a few pregabalin prescriptions (n = 4).
Conclusions
Clinicians in this study frequently prescribed antidepressants to treat PTSD, as recommended. However, most of the antidepressants used were not recommended in the VA/DoD guidelines. Benzodiazepines and Z-drugs remained widely used, although they are not recommended.
Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008.Method: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments.Result: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders.For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs.Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated.For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option.Conclusion: OCD and PTSD can be effectively treated with CBT and medications.
Aim:
This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders (published in 2002, revised in 2008).
Method:
A consensus panel of 33 international experts representing 22 countries developed recommendations based on efficacy and acceptability of available treatments. In total, 1007 RCTs for the treatment of these disorders in adults, adolescents, and children with medications, psychotherapy and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medications.
Result:
This paper, Part I, contains recommendations for the treatment of panic disorder/agoraphobia (PDA), generalised anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, mixed anxiety disorders in children and adolescents, separation anxiety and selective mutism. Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line medications. Cognitive behavioural therapy (CBT) is the first-line psychotherapy for anxiety disorders. The expert panel also made recommendations for patients not responding to standard treatments and recommendations against interventions with insufficient evidence.
Conclusion:
It is the goal of this initiative to provide treatment guidance for these disorders that has validity throughout the world.
Introduction
Despite promising results from several randomized controlled trials (RCTs) and meta-analyses, the efficacy of r-TMS as a treatment for OCD remains controversial, at least in part owing to inconsistency in the trial methodologies and heterogeneity in the trial outcomes. This meta-analysis attempts to explain some of this heterogeneity by comparing the efficacy of r-TMS in patients with or without resistance to treatment with selective serotonin reuptake inhibitors (SSRI), defined using standardized criteria.
Methods
We conducted a pre-registered (PROSPERO ID: 241381) systematic review and meta-analysis. English language articles reporting blinded RCTs were retrieved from searches using MEDLINE, PsycINFO, and Cochrane Library databases. Studies were subjected to subgroup analysis based on four stages of treatment resistance, defined using an adaptation of published criteria (1 = not treatment resistant, 2 = one SSRI trial failed, 3 = two SSRI trials failed, 4 = two SSRI trials failed plus one or more CBT trial failed). Meta-regression analyses investigated patient and methodological factors (age, duration of OCD, illness severity, stage of treatment-resistance, or researcher allegiance) as possible moderators of effect size.
Results
Twenty-five independent comparisons (23 studies) were included. Overall, r-TMS showed a medium-sized reduction of Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores (Hedge's g: -0.47; 95%CI: - 0.67 to −0.27) with moderate heterogeneity (I² = 39.8%). Assessment of publication bias using Trim and Fill analysis suggested a reduced effect size that remained significant (g: -0.29; 95%CI: −0.51 to −0.07). Subgroup analysis found that those studies including patients non-resistant to SSRI (stage 1) (g: -0.65; 95%CI: −1.05 to −0.25, k = 7) or with low SSRI-resistance (stage 2) (g:-0.47; 95%CI: −0.86 to −0.09, k = 6) produced statistically significant results with low heterogeneity, while studies including more highly resistant patients at stage 3 (g: −0.39; 95%CI: −0.90 to 0.11, k = 4) and stage 4 (g: -0.36; 95%CI: −0.75 to 0.03, k = 8) did not. Intriguingly, the only significant moderator of the effect size found by meta-regression was the severity of baseline depressive symptoms. All trials showed evidence of researcher allegiance in favour of the intervention and therefore caution is required in interpreting the reported effect sizes.
Conclusion
This meta-analysis shows that r-TMS is an effective treatment for OCD, but largely for those not resistant to SSRI or failing to respond to only one SSRI trial. As a consequence, r-TMS may be best implemented earlier in the care pathway. These findings would have major implications for clinical service development, but further well-powered RCTs, which eliminate bias from researcher allegiance, are needed before definitive conclusions can be drawn.
The results of a clinical outcome study (N = 57) comparing behavior therapy directed at panic disorder (panic control treatment [PCT]) with alprazolam were reported. These conditions were compared with a medication placebo and a waiting-list control group. Patterns of results on measures of panic attacks, generalized anxiety, and global clinical ratings reveal that PCT was significantly more effective than placebo and waiting-list conditions on most measures. The alprazolam group differed significantly from neither PCT nor placebo. The percentage of clients completing the study who were free of panic attacks following PCT was 87%, compared with 50% for alprazolam, 36% for placebo, and 33% for the waiting-list group. Since alprazolam may work more quickly than PCT but may also interfere with the effects of behavioral treatment, these data suggest a series of studies on the feasibility of integrating these treatments and on the precise patterns and mechanisms of action of various successful treatment approaches to panic disorder.
In a meta-analysis, the authors compared the effectiveness of psychological and pharmacological treatments for panic disorder. Percentage of agoraphobic subjects in the sample and duration of the illness were unrelated to effect size (ES). Type of dependent variable was generally unrelated to treatment outcome, although behavioral measures yielded significantly smaller ESs. Dependent measures of general anxiety, avoidance, and panic attacks yielded larger ESs than did depression measures. Choice of control was related to ES, with comparisons with placebo controls greater than comparisons with exposure-only or "other treatment" controls. Psychological coping strategies involving relaxation training, cognitive restructuring, and exposure yielded the most consistent ESs; flooding and combination treatments (psychological and pharmacological) yielded the next most consistent ESs. Antidepressants were the most effective pharmacological intervention.
Objective: The relative short-term efficacy and long-term benefits of pharmacologic versus psychotherapeutic interventions have not been studied for posttraumatic stress disorder (PTSD). This study compared the efficacy of a selective serotonin reuptake inhibitor (SSRI), fluoxetine, with a psychotherapeutic treatment, eye movement desensitization and reprocessing (EMDR), and pill placebo and measured maintenance of treatment gains at 6-month follow-up. Method: Eighty-eight PTSD subjects diagnosed according to DSM-IV criteria were randomly assigned to EMDR, fluoxetine, or pill placebo. They received 8 weeks of treatment and were assessed by blind raters posttreatment and at 6-month follow-up. The primary outcome measure was the Clinician-Administered PTSD Scale, DSM-IV version, and the secondary outcome measure was the Beck Depression Inventory-II. The study ran from July 2000 through July 2003. Results: The psychotherapy intervention was more successful than pharmacotherapy in achieving sustained reductions in PTSD and depression symptoms, but this benefit accrued primarily for adult-onset trauma survivors. At 6-month follow-up, 75.0% of adult-onset versus 33.3% of child-onset trauma subjects receiving EMDR achieved asymptomatic end-state functioning compared with none in the fluoxetine group. For most childhood-onset trauma patients, neither treatment produced complete symptom remission. Conclusions: This study supports the efficacy of brief EMDR treatment to produce substantial and sustained reduction of PTSD and depression in most victims of adult-onset trauma. It suggests a role for SSRIs as a reliable first-line intervention to achieve moderate symptom relief for adult victims of childhood-onset trauma. Future research should assess the impact of lengthier intervention, combination treatments, and treatment sequencing on the resolution of PTSD in adults with childhood-onset trauma.
These guidelines for the biological treatment of schizophrenia were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of schizophrenia, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating people with schizophrenia. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for schizophrenia, as well as from meta-analyses, reviews and randomised clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into four levels of evidence (A/D). This first part of the guidelines covers disease definition, classification, epidemiology and course of schizophrenia, as well as the management of the acute phase treatment. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication, other pharmacological treatment options, electroconvulsive therapy, adjunctive and novel therapeutic strategies) of adults suffering from schizophrenia.
Background: The goal of our study is to assess whether transcranial magnetic stimulation (rTMS) would facilitate the effect of antidepressant in OCD patients. Method: The aim of the randomized, double-blind, sham controlled study was to compare the 2 and 4 week efficacy of the 10 sessions rTMS with sham rTMS in serotonin reuptake inhibitor resistant OCD patient. Thirty three right-handed patients were randomly assigned to either active rTMS or to sham rTMS. Active rTMS with the frequency of 1 Hz at 110% of motor threshold (MT) was administered over the left dorso-lateral prefrontal cortex. The same time schedule was used for sham administration. Thirty patients finished the study, three patients' dropped out at the beginning. Psychopathology was assessed by CGI, HAMA, Y-BOCS and BAI before the treatment, immediately after the experimental treatment, and 2 weeks after the experimental treatment by an independent reviewer. Results: Both groups improved during the study period but the treatment effect did not differ between them in any of the instruments. Conclusion: Low frequency rTMS administered over the left dorso-lateral prefrontal cortex during 10 daily sessions did not differ from sham rTMS in facilitating the effect of serotonin reuptake inhibitors in OCD patients.
There is evidence that panic disorder and major depression might share some common neurobiological factors. This would be consistent with the fact that most antidepressant drugs are effective in preventing panic attacks.
This is a case report of a 40 year old woman who was suffering from a panic disorder. Following the discontinuation of a long-term lorazepam treatment, she developed severe depressive symptoms. The depressive syndrome improved rapidly with amitriptyline (150 mg/day), but the panic attacks persisted. Twelve weeks later, amitriptyline was replaced by clomipramine (150 mg/day), the dosage of which was increased to 225 mg/day three weeks later. The patient remained anxious with no resolution of her panic attacks. Two weeks later, lithium carbonate (900 mg/day) was added to clomipramine. Sixty hours later, a dramatic improvement was observed. The lithium plasma level was 0.8 mEq/L. Because of some tremors, lithium was discontinued five days later. Within four days, the anxiety as well as the panic attacks reappeared. Lithium carbonate (600 mg/day) was then resumed. Forty-eight hours later, the patient was showing a clinical improvement similar to that observed following the first addition of lithium. She remained symptom free with the maintenance of the drug combination.
To date, several reports have confirmed the beneficial effect of adding lithium to a tricyclic antidepressant drug in resistant major depression. However, we believe that the present case reprot is the first one documenting the augmentation of a tricyclic antidepressant drug by lithium in a patient suffering from a panic disorder.
These results lend support to the earlier findings that imipramine, flooding, and their combined treatment are highly and equally effective and that the nonspecific treatment is significantly inferior to these active treatment conditions. There was neither statistical nor clinical evidence for a synergistic or additive action in the combined treatment. The results also suggest that the antiphobic effect of imipramine, in contrast to flooding, might be related to its antidepressant effect. Interpretation of these results should take into account the fact that all patients, including those in the imipramine group, received systematic instructions to practice exposure to phobic stimuli, an effective behavioral intervention in its own right (Mathews et al 1981).
Context No large-scale posttraumatic stress disorder drug trials have been conducted to evaluate treatment effects beyond 12 weeks outside of those with selective serotonin reuptake inhibitors. Objective To evaluate the efficacy of venlafaxine extended release (ER), a serotonin norepinephrine reuptake inhibitor, in posttraumatic stress disorder. Design 6-month, double-blind, placebo-controlled trial. Setting International study at 56 sites. Patients Adult outpatients (N = 329) with a primary diagnosis of posttraumatic stress disorder as defined in the DSM-IV, symptoms for 6 months or longer, and a 17-item Clinician-Administered Posttraumatic Stress Disorder Scale score of 60 or higher. Intervention Patients randomly assigned to receive flexible doses of venlafaxine ER (37.5-300 mg/d) or placebo for 24 weeks. Main Outcome Measures Primary measure was the change from baseline in the Clinician-Administered Posttraumatic Stress Disorder Scale score. Secondary measures included remission, defined as a Clinician-Administered Posttraumatic Stress Disorder Scale score of 20 or lower, and changes in symptom cluster scores, frequency of remission, and time to remission. Measures of stress vulnerability, resilience, depression, quality of life, functioning, and global illness severity were also taken. Results Mean changes from baseline in Clinician-Administered Posttraumatic Stress Disorder Scale total scores at end point were –51.7 for venlafaxine ER and –43.9 for placebo (P = .006). Improvement was significantly greater for the venlafaxine ER group than for the placebo group in cluster scores for reexperiencing (P = .008) and avoidance/numbing (P = .006), but not for hyperarousal. Remission rates were 50.9% for venlafaxine ER and 37.5% for placebo (P = .01). The venlafaxine ER group also showed significantly greater improvement at end point than the placebo group (P<.05) on all other reported outcome measures. The mean maximum daily dose of venlafaxine ER was 221.5 mg/d. Withdrawal rates were similar between groups with no significant difference in dropouts attributable to adverse events. Conclusion In this study, venlafaxine ER was effective and well tolerated in short-term and continuation treatment of patients with posttraumatic stress disorder.
Several issues remain to be ascertained beyond the acute response to imipramine hydrochloride in patients with panic disorder. Study 1 consisted of a prospective, systematic characterization of half-dose 12-month maintenance in patients with panic disorder with agoraphobia who had shown marked and stable response to 6 months of acute-phase treatment with imipramine. Study 2 assessed the 6-month cumulative relapse rate following discontinuation of acute-phase imipramine treatment in a comparable sample of patients. The same assessment battery was used in both studies, and the integrity of experimental drug conditions was verified by plasma drug level determinations. In contrast to the high relapse rate following discontinuation of acute-phase treatment, none of the patients showed relapse or had sustained worsening in panic or phobia measures during the half-dose maintenance period. The results underscore the importance of pharmacological prophylaxis and provide empirical guidelines for a successful low-dose maintenance regimen for patients with panic disorder and agoraphobia who respond markedly to imipramine.
Background Obsessive-compulsive disorder (OCD) is a common psychiatric condition that usually emerges during childhood or adolescence. Over 80% of individuals with OCD have their onset before age 18 years. Epidemiologic studies suggest a prevalence of 1 -2 for adolescents.
Method This article reviews current knowledge of paediatric OCD in the following areas: age of onset, nosology and classification, subtypes, prevalence, aetiology, pathophysiology, assessment, prognosis and treatment.
Results Essential components of treatment include long-term commitment, care management and illness education. Specific components of treatment include cognitive-behavioural therapy, parent behaviour management training and medication.
Conclusions The most effective treatments are selective serotonin reuptake inhibitors (e.g. fluvoxamine, sertraline) and exposure/response prevention.
Background: Central nervous system (CNS) adrenergic hyperresponsiveness may be involved in the pathophysiology of posttraumatic stress disorder (PTSD). Two Vietnam combat veterans with PTSD prescribed the centrally active alpha(1)-adrenergic antagonist prazosin for symptoms of benign prostatic hypertrophy unexpectedly reported elimination of combat trauma nightmares. This observation prompted an open-label feasibility trial of prazosin for combat trauma nightmares in chronic combat-induced PTSD. Method: Four consecutively identified combat veterans with chronic DSM-IV PTSD and severe intractable combat trauma nightmares participated in an 8-week open trial of escalating-dose prazosin. Nightmare severity response was rated using the nightmare item of the Clinician Administered PTSD Scale and the Clinical Global Impressions-Change scale. Results: The 2 patients who achieved a daily prazosin dose of at lease 5 mg were markedly improved, with complete elimination of trauma nightmares and resumption of normal dreaming. The 2 subjects limited to 2 mg of prazosin to avoid excessive blood pressure reduction were moderately improved with at least 50% reduction in nightmare severity. Conclusion: These clinical observations, together with neurobiological evidence for alpha(1)-adrenergic regulation of CNS neurobiological systems relevant to PTSD, provide rationale for placebo-controlled trials of prazosin for PTSD combat trauma nightmares.
Background: The objective of this randomized, double-blind study was to compare the efficacy and safety of venlafaxine extended release (XR) and buspirone in outpatients with generalized anxiety disorder (GAD) but without concomitant major depressive disorder. Method: Male and female outpatients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with either venlafaxine XR (75 or 150 mg/day), buspirone (30 mg/day in 3 divided doses), or placebo for 8 weeks. The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale (CGI) scores. Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale (HAD). Results: The efficacy analysis included 365 patients and the safety analysis, 405. At week 8, adjusted mean HAM-A psychic anxiety, anxious mood, and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients. On the HAD anxiety subscale, venlafaxine XR, 75 or 150 mg/day, was significantly more efficacious than placebo at all time points except weeks 1 (both dosages) and 2 (150-mg/day dosage only) and significantly more efficacious than buspirone at all time points except week 1. On the CGI-Improvement scale, scores for venlafaxine XR (both dosages) and buspirone were numerically superior to those for placebo at all time points, and statistical significance was observed at weeks 3, 4, 6, and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone. The adverse events were not essentially different between treatment groups. Conclusion: Venlafaxine XR is an effective, safe, and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder. This agent was significantly superior to buspirone on the HAD anxiety subscale. Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response.
Background: Despite the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessive-compulsive disorder, a significant number of patients show no or only partial remission of symptoms. Some evidence exists to suggest that risperidone augmentation can be helpful in treating this refractory group. The efficacy of other atypical antipsychotic agents, such as olanzapine, in augmenting SSRIs in refractory obsessive-compulsive patients has yet to be systematically investigated. Method: A series of 10 patients with DSM-IV obsessive-compulsive disorder showing significant residual symptoms following an adequate SSRI trial (12 weeks) were given open-label olanzapine augmentation for a minimum of an additional 8 weeks. Treatment response was assessed using the Yale-Brown Obsessive Compulsive Scale and the Clinical Global Impressions scale. Results: Nine of the 10 patients in this series treated with olanzapine and an SSRI completed the 8-week augmentation trial, Of these, 4 demonstrated a complete remission or major improvement in obsessive-compulsive symptoms, 3 had partial remission, and 2 experienced no benefit. Nine patients experienced minimal adverse effects, primarily sedation, which did not interfere with continuing treatment. One patient discontinued olanzapine owing to excessive sedation. Conclusion: The results of this preliminary, open-label trial suggest that olanzapine may be effective in augmenting ongoing SSRI treatment for a portion of patients with obsessive-compulsive disorder refractory to SSRI treatment. Larger, placebo-controlled trials appear warranted to investigate the clinical efficacy and tolerability of olanzapine augmentation of SSRI treatment in SSRI-refractory obsessive-compulsive disorder.
To investigate whether alprazolam (ALP) coprescription early in the imipramine (IMI) treatment of panic disorder would improve overall treatment response to IMI alone, 48 panic disorder patients were randomly assigned to receive either IMI plus placebo or IMI plus ALP for 4-6 weeks, followed by 2 weeks of IMI plus placebo-ALP taper and 2 more weeks of IMI alone. Although patients in the IMI plus ALP group improved more quickly, significantly more patients in the IMI plus ALP group could not follow the taper schedule. The results suggest that studies employing other benzodiazepines or other ALP dosage or taper schedules would be required to demonstrate any benefit for the IMI plus early benzodiazepine cotreatment strategy over IMI alone in the routine pharmacologic management of panic disorder.
This study examined the effects of cognitive- behavior therapy (CBT) compared with traditional behavior therapy (exposure and response prevention [ERP]) in the group treatment of obsessive-compulsive disorder. Of the 76 participants who started treatment, 38 were wait-listed for 3 months before treatment to assess possible course effects. Both treatments were superior to the control condition in symptom reduction, with ERP being marginally more effective than CBT by end of treatment and again at 3-month follow-up. In terms of clinically significant improvement, treatment groups were equivalent on the conclusion of treatment, but 3 months later significantly more ERP participants met criteria for recovered status. Only 1 of 7 belief measures changed with treatment improvement, and the extent of this cognitive change was similar between CBT and ERP groups. Discussion includes consideration of optimal formats for the delivery of different types of treatment.
Seventy-two social phobics were Tandomly assigned to behavioral (flooding) or drug treatment with atenolol or placebo. Treatment was administered over a 3-month period of time, and duration of treatment effects was determined at a 6-month follow-up assessment. Multiple measures of outcome were used, including self-report, clinician ratings (including assessment by independent evaluators), behavioral assessment, and performance on composite indexes. The results indicated that flooding consistently was superior to placebo, whereas atenolol was not. Flooding also was superior to atenolol on behavioral measures and composite indexes. Those subjects who improved during treatment maintained gains at the 6-month follow-up regardless of whether they received flooding or atenolol. The variability of outcome on different measures in social phobia research is discussed, and the need for broad-based treatment strategies to address the pervasive deficits associated with social phobia is noted.
The relative effectiveness of the available treatments for panic disorder may best be understood in the context of the longitudinal course of the disorder. This study examines a number of clinically relevant issues, including long-term outcome after acute treatment, the proportion of patients remaining on single-agent treatment or requiring multiple medications or nonpharmacologic interventions over time, evidence for dose escalation during maintenance high-potency benzodiazepine therapy, and predictors of acute and long-term response to treatment. Fifty-nine panic disorder patients originally randomized to treatment in a controlled trial comparing alprazolam, clonazepam, and placebo were reevaluated in a follow-up study. At a mean follow-up of 1.5 years, 78% of patients remained on medication and the mean dosage of alprazolam and clonazepam did not increase. Our data suggest that most patients maintain benefit with long-term pharmacotherapy but that residual symptomatology may require more intensive or additional treatment strategies. Response at the endpoint of the acute trial was significantly associated with pretrial baseline Clinical Global Impression Scale score and the presence of dysthymia. Poor outcome at follow-up was associated with total duration of the disorder, agoraphobic subtype, and the presence of comorbid social phobia. We underscore the potential importance of comorbid affective and anxiety disorders as well as phobic patterns in determining long-term response to treatment.
In a controlled clinical trial, 57 Ss meeting DSM—III—R criteria for generalized anxiety disorder, and fulfilling an additional severity criterion, were randomly allocated to cognitive behavior therapy (CBT), behavior therapy (BT), or a waiting-list control group. Individual treatment lasted 4—12 sessions; independent assessments were made before treatment, after treatment, and 6 months later, and additional follow-up data were collected after an interval of approximately 18 months. Results show a clear advantage for CBT over BT. A consistent pattern of change favoring CBT was evident in measures of anxiety, depression, and cognition. Ss were lost from the BT group, but there was no attrition from the CBT group. Treatment integrity was double-checked in England and in Holland, and special efforts were made to reduce error variance. Possible explanations for the superiority of CBT are discussed.
Among 79 volunteer, unpaid, family doctor-referred psychiatric out patients with DSM III-R panic disorder, with and without agoraphobia, 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months. All subjects received one hour per week concurrent behavioural counselling in the acute phase. Of 13 dropouts in the first 3 weeks, 9 (of 27) were on clomipramine, 2 (of 26) were on lofepramine and 2 (of 26) were on placebo. The high (30%) early dropout from the clomipramine group was largely due to medication intolerance. Both drugs were superior to placebo by the end of week 6 on several standard rating scales but not on panic attack frequency. No significant differences in efficacy were found between the two drugs tested to the end of 6 months. No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24. The study provides evidence that both drugs, in the dosages used, are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy.
Research reveals that traumatic events are frequent. The reactions to trauma can be diagnosed and specified by modern psychiatric diagnostic systems. Comorbidity of several psychiatric disorders is often found. For most of the patients symptoms remit within some weeks whereas a considerable minority develop chronic symptomatology. The development of PTSD is a complex process with several factors influencing each other. Psychopharmacological or psychotherapeutic treatment may reduce even chronic PTSD-symptoms within some weeks. Modern psychiatric diagnostic systems and a new version of the German guidelines for litigation facilitate the litigation process.
Background: The prevalence of generalized anxiety disorder (GAD) represents an important public health issue, Hydroxyzine. an antagonist of histamine receptors, showed both efficacy and safety in previous short-term double-blind studies over placebo in this pathology. The aim of the current study was to confirm those positive results over a 3-month period in adult outpatients. Method: This multicenter, parallel (hydroxyzine [50 mg/day]; bromazepam [6 mg/day]), randomized, double-blind, placebo-controlled trial included 2 weeks of single-blind run-in placebo, 12 weeks of double-blind randomized treatment, and 4 weeks of single-blind run-out placebo. Three hundred thirty-four of 369 selected outpatients with a diagnosis of GAD according to DSM-IV criteria and a Hamilton Rating Scale for Anxiety (HAM-A) total score ≥ 20 were randomized before entering the double-blind period. The primary outcome criterion was the change in the HAM-A score from baseline to 12 weeks of double-blind treatment with hydroxyzine compared with placebo. Results: In the intent-to-treat analysis, the mean ±SD change in HAM-A scores from baseline to endpoint was -12.16 ±7.74 for hydroxyzine and -9.64 ±7.74 for placebo (p =.019). Results at endpoint for percentage of responders (p =.003) and remission rates (p =.028). Clinical Global Impressions-Severity scale score (p =.001), maintenance of efficacy (p =.022), and Hospital Anxiety and Depression scale score on day 84 (p =.008) also confirmed the efficacy of hydroxyzine over placebo. The study showed no statistically significant difference between hydroxyzine and bromazepam. Except for drowsiness, which was more frequent with bromazepam. safety results were comparable in the 3 groups. Conclusion: Hydroxyzine showed both efficacy and safety in the treatment of GAD and appears to be an effective alternative treatment to benzodiazepine prescription.
Depression is a common condition among women of reproductive age, and selective serotonin reuptake inhibitors (SSRIs) are frequently used for the treatment of depression. However, recent reports regarding SSRI use during pregnancy have raised concerns about fetal cardiac defects, newborn persistent pulmonary hypertension, and other negative effects. The potential risks associated with SSRI use throughout pregnancy must be considered in the context of the risk of relapse of depression if maintenance treatment is discontinued. The American College of Obstetricians and Gynecologists' Committee on Obstetric Practice recommends that treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible.
The primary objectives of this large multicenter study (n = 578) were to determine the efficacy and safety of moclobemide, 300 or 600 mg per day, for the treatment of social phobia. A double-blind fixed-dose parallel group study was conducted to compare the two different doses of moclobemide to placebo. After a 1-week placebo run-in period, patients were randomly assigned to one of the three treatment groups to receive the test compound for a 12-week period. Assessments were performed at screen, on baseline and on weeks 1, 2, 3, 4, 6, 8, 10, and 12. There were consistent, reliable and clinically meaningful drug effects and indications of a dose-response relationship. Statistical analysis of the results at both weeks 8 and 12 showed that 600 mg of moclobemide was effective and statistically significantly superior to placebo. The 300 mg dose also showed better efficacy than placebo on all measures of efficacy, and about half of them were statistically significantly different from placebo. Moclobemide was well tolerated. Adverse events, except for insomnia, were neither dose-related nor were there significant drug-placebo differences. The results indicate that 600 mg of moclobemide per day given b.i.d. is effective in social phobia, reducing the symptoms and the impairment associated with the disorder. The compound is well tolerated and safe.
• Two double-blind studies at 21 centers evaluated the therapeutic efficacy, safety, and tolerability of up to 300 mg/d of clomipramine hydrochloride or an equivalent number of placebo capsules in the treatment of 520 patients with obsessive-compulsive disorder, of whom 239 had had the disorder for at least 2 years (study 1) and 281 had been ill for at least 1 year (study 2). On the two principal measures of the severity of the disorder, ie, the Yale-Brown Obsessive Compulsive Scale and the National Institute of Mental Health Global Obsessive Compulsive Scale, clomipramine was significantly more effective than placebo in both studies. The mean reduction in the Yale-Brown Obsessive Compulsive Scale score at the end of 10 weeks of treatment was 38% and 44% in studies 1 and 2, respectively, for the clomipramine-treated patients and 3% and 5% for the placebotreated patients. The drug was also found to be superior on the basis of the physicians' and patients' evaluations of global therapeutic change. The most frequently observed adverse effects during clomipramine therapy were those typically associated with tricyclic antidepressant drugs. Although uncommon, the occurrence of seizures and elevated aminotransferase values are potentially serious side effects of clomipramine. Clomipramine was generally well tolerated and was effective in reducing obsessive and compulsive symptoms.
Errors in Byline, Author Affiliations, and Acknowledgment. In the Original Article titled “Prevalence, Severity, and Comorbidity of 12-Month DSM-IV Disorders in the National Comorbidity Survey Replication,” published in the June issue of the ARCHIVES (2005;62:617-627), an author’s name was inadvertently omitted from the byline on page 617. The byline should have appeared as follows: “Ronald C. Kessler, PhD; Wai Tat Chiu, AM; Olga Demler, MA, MS; Kathleen R. Merikangas, PhD; Ellen E. Walters, MS.” Also on that page, the affiliations paragraph should have appeared as follows: Department of Health Care Policy, Harvard Medical School, Boston, Mass (Drs Kessler, Chiu, Demler, and Walters); Section on Developmental Genetic Epidemiology, National Institute of Mental Health, Bethesda, Md (Dr Merikangas). On page 626, the acknowledgment paragraph should have appeared as follows: We thank Jerry Garcia, BA, Sara Belopavlovich, BA, Eric Bourke, BA, and Todd Strauss, MAT, for assistance with manuscript preparation and the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork, and consultation on the data analysis. We appreciate the helpful comments of William Eaton, PhD, Michael Von Korff, ScD, and Hans-Ulrich Wittchen, PhD, on earlier manuscripts. Online versions of this article on the Archives of General Psychiatry Web site were corrected on June 10, 2005.
This paper reviews the treatment of obsessive-compulsive disorder (OCD) in children and adolescents. Focusing on clinical features of the disorder and its treatment particular to pediatric onset, diagnosis, assessment, and behavioral, pharmacological, as well as new investigative treatments are covered. Adaptation of cognitive-behavioral therapy for children and adolescents, use of augmenting agents in drug treatment, and subtyping of OCD cases are developments relevant for current practice.
• Forty-eight children and adolescents with severe primary obsessive-compulsive disorder completed a 10-week doubleblind crossover trial of clomipramine hydrochloride (mean dose [±SD], 150±53 mg/d) and desipramine hydrochloride (mean dose [±SD], 153±55 mg/d). Clomipramine was clearly superior to desipramine in significantly reducing obsessive-compulsive symptoms. Age at onset, duration and severity of illness, type of symptom, and plasma drug concentrations did not predict clinical response to clomipramine. Sixty-four percent of patients who received clomipramine as their first active treatment showed at least some sign of relapse during desipramine treatment. We further document the specificity of the antiobsessional effect of clomipramine and the need for maintenance treatment.
Context:
The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy.
Objective:
To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD.
Design, setting, and participants:
The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002.
Interventions:
Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks.
Main outcome measures:
Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10.
Results:
Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others.
Conclusion:
Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.
Background: The purpose of this multicenter, double-blind, placebo-controlled study was to evaluate the efficacy and safety of optimized dosages of clonazepam for the treatment of panic disorder and assess the tolerability of a schedule for gradual discontinuation. Method: Adult patients with panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to receive either placebo or clonazepam in individually adjusted doses over 3 weeks to approximate an optimal dosage, which was then maintained for an additional 3 weeks, amounting to a 6-week therapeutic phase. The daily dose range was 0.25 to 4.0 mg administered in 2 divided doses. In the following 7-week discontinuance phase, the doses were tapered gradually to cessation. Results: At the therapeutic endpoint, clonazepam (N = 222) proved clinically and statistically superior to placebo (N = 216) in change in the number of panic attacks and in Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Change scores, Patient's Global Impression of Change scores, amount of fear and avoidance associated with phobic symptoms, and duration of anticipatory anxiety. The gradual tapering of clonazepam was not associated with symptoms suggestive of withdrawal syndrome. Although patients taking clonazepam experienced some clinical worsening compared with the status achieved at endpoint, particularly in terms of number of panic attacks, no deterioration was observed using their condition at baseline as point of reference. No overall evidence of rebound was found. All regimens were generally well tolerated. Somnolence was the main adverse event associated with clonazepam therapy. The percentage of patients who reported adverse events was higher in the clonazepam group than in the placebo group, as was the mean number of adverse events per patient. Conclusion: In this placebo-controlled trial, clonazepam was an efficacious and safe short-term treatment of the symptoms of panic disorder. Discontinuance during and after slow tapering was well tolerated.
This study examined the use patterns and efficacy of the high potency benzodiazepine (HPB) clonazepam in panic patients who were treated and followed naturalistically in the Massachusetts General Hospital Longitudinal Study of Panic Disorder. Of 204 patients followed over a 2-year period, 46 percent were receiving clonazepam alone or in combination with an antidepressant. Treatment was not controlled at initial evaluation or during the follow-up period. The main variables assessed in this analysis included global severity of the panic disorder and stability of clonazepam dose. All treatment groups tended to improve over time without significant differences in outcome between groups. Clonazepam doses remained stable over time. Results of this study suggest that treatment of panic disorder with the HPB clonazepam achieved and maintained a therapeutic benefit similar to that obtained with alternative pharmacologic treatments, without the development of tolerance as manifested by dose escalation or worsening of clinical status.
Objectives:
To determine the effectiveness of fluoxetine hydrochloride at fixed doses of 20 mg/d, 40 mg/d, and 60 mg/d in patients with obsessive-compulsive disorder (OCD) and to evaluate its safety.Methods:
Fixed-dose fluoxetine hydrochloride (20 mg/d, 40 mg/d, 60 mg/d) was compared with placebo in two randomized, double-blind, parallel, 13-week trials of identical design in 355 outpatients with OCD aged 15 to 70 years (DSM-III-R criteria; 1 year's duration or longer; depression secondary if present).Results:
Fluoxetine (all doses) was significantly (P±001) superior to placebo on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (mean baseline-to-end—point decrease, 4.6,5.5, and 6.5 vs 0.9, respectively, studies pooled) and other efficacy measures (P±01). A trend suggesting greater efficacy at 60 mg/d was observed. Most patients (79.2%) completed the study. Eight adverse events were statistically significantly more frequent with fluoxetine and one, with placebo. For some events, incidence tended to increase with increasing dosage; however, few patients discontinued treatment for any single event.Conclusion:
Fluoxetine was associated with a statistically significant reduction in OCD severity, including time engaged in obsessional and/or compulsive behaviors. Adverse events infrequently led to study discontinuation.
In a contribution to the January 1995 issue of the Archives comparing the efficacy and tolerability of clomipramine, fluoxetine, fluvoxamine, and sertraline, Greist et al,1 using a method of meta-analysis, found all 4 agents to be effective in the treatment of patients who have obsessive-compulsive disorder (OCD). Whereas all 4 are serotonin-transport inhibitors, clomipramine, with its noradrenergic transport—inhibition component, most notably showed an efficacy advantage. With regard to this finding, Greist et al stated, "It seems that something may be missing in fluoxetine, fluvoxamine, and sertraline that clomipramine contains." They posed the question, "Will agents such as... venlafaxine hydrochloride, which have selective and potent serotonin and noradrenergic transport inhibition and a better side-effect profile than clomipramine, work well in treating OCD?" I wish to respond by reporting our limited experience with venlafaxine therapy in such patients. Research that we have conducted suggests that the preliminary answer to this
Objective:
The current study examines whether antidepressants, contrary to current thinking, are safe and effective treatments for generalized anxiety disorder (GAD) not complicated by depression or panic disorder.Design:
Randomized, double-blind, placebocontrolled, flexible-dose, 8-week treatment study comparing imipramine hydrochloride (mean maximum daily dose, 143 mg), trazodone hydrochloride (255 mg), and diazepam (26 mg).Patients:
Two hundred thirty patients with a DSM-III diagnosis of GAD in whom major depression and panic disorder has been excluded, and who had a Hamilton Anxiety Scale total score of at least 18.Setting:
Seventy-five percent of patients were treated in family practice settings in the community, with the remainder treated in psychiatric practices, either academic or private.Results:
Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment, with somatic symptoms being most responsive. From week 3 through week 8 trazodone achieved comparable, and imipramine somewhat better, anxiolytic efficacy when compared with diazepam, with psychic symptoms of tension, apprehension, and worry being more responsive to the antidepressants. Among completers, moderate to marked improvement was reported by 73% of patients treated with imipramine, 69% of patients treated with trazodone, 66% of patients treated with diazepam, but only 47% of patients treated with placebo. Overall, patients treated with antidepressants reported a higher rate of adverse effects than diazepam-treated patients, but attention rates were the same across all treatments.Conclusions:
The results of the study need replication, but suggest a potentially important role for antidepressants, particularly imipramine, in patients suffering from GAD.
We studied the efficacy of propanolol (Inderal) compared to alprazolam (Xanax) in 29 patients with a diagnosis of agoraphobia with panic disorder or panic disorder with or without limited phobic avoidance in a 6-week double-blind controlled experiment. Alprazolam is effective in those syndromes, whereas to date only negative or ambiguous results had been reported for propranolol. Fourteen patients received a mean daily dose of 5.0 +/- 2.3 mg of alprazolam and 15 patients received 182.0 +/- 60.5 mg mean daily dose of propranolol. We found both drugs to be effective to suppress panic attacks and reduce avoidance behavior. The only significant between-drug difference was a more rapid onset of alprazolam's panicolytic effect. Propranolol merits further study. We suggest patients worthy of a clinical trial.
The Cross-National Collaborative Panic Study, Phase Two, compared alprazolam with imipramine and with placebo in a sample of 1168 randomly assigned subjects. The study, conducted at 12 centres, assessed clinical change over eight weeks of double-blind drug treatment. Improvement occurred with alprazolam by week 1 and 2, and with imipramine by week 4. By the end of week 8, however, the effects of the two active drugs were similar to each other, and both were superior to placebo for most outcome measures.