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The American Journal of Psychiatry Mar 2017Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors... (Review)
Review
OBJECTIVE
Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines.
METHOD
A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus.
RESULTS
Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting of minimum adherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients.
CONCLUSIONS
There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation.
Topics: Antipsychotic Agents; Brief Psychiatric Rating Scale; Drug Resistance; Humans; Practice Guidelines as Topic; Psychometrics; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology
PubMed: 27919182
DOI: 10.1176/appi.ajp.2016.16050503 -
Canadian Journal of Psychiatry. Revue... Sep 2017The present guidelines address the pharmacotherapy of schizophrenia in adults across different stages, phases, and symptom domains. (Review)
Review
OBJECTIVE
The present guidelines address the pharmacotherapy of schizophrenia in adults across different stages, phases, and symptom domains.
METHOD
Guidelines were developed using the ADAPTE process, which takes advantage of existing guidelines. Six guidelines were identified for adaptation, with recommendations extracted from each. For those specific to the pharmacotherapy of schizophrenia in adults, a working group selected between guidelines and recommendations to create an adapted guideline.
RESULTS
Recommendations can be categorized into 6 areas that include 1) first-episode schizophrenia, 2) acute exacerbation, 3) relapse prevention and maintenance treatment, 4) treatment-resistant schizophrenia, 5) clozapine-resistant schizophrenia, and 6) specific symptom domains. For each category, recommendations are made based on the available evidence, which is discussed and linked to other established guidelines.
CONCLUSIONS
In most cases, evidence-based recommendations are made that can be used to guide current clinical treatment and decision making. Notably, however, there is a paucity of established evidence to guide treatment decision making in the case of clozapine-resistant schizophrenia, a subsample that represents a sizable proportion of those with schizophrenia.
Topics: Adult; Antipsychotic Agents; Canada; Evidence-Based Medicine; Humans; Practice Guidelines as Topic; Schizophrenia
PubMed: 28703015
DOI: 10.1177/0706743717720448 -
The International Journal of... Mar 2023Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of...
Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.
Topics: Hallucinogens; Default Mode Network; Psilocybin; Lysergic Acid Diethylamide; Brain; Magnetic Resonance Imaging
PubMed: 36272145
DOI: 10.1093/ijnp/pyac074 -
Current Neuropharmacology 2015The prevalence and comorbidity of psychiatric disorders such as depression, anxiety and insomnia are very common. These well-known forms of psychiatric disorders have... (Review)
Review
The prevalence and comorbidity of psychiatric disorders such as depression, anxiety and insomnia are very common. These well-known forms of psychiatric disorders have been affecting many people from all around the world. Herb alone, as well as herbal formula, is commonly prescribed for the therapies of mental illnesses. Since various adverse events of western medication exist, the number of people who use herbs to benefit their health is increasing. Over the past decades, the exploration in the area of herbal psychopharmacology has received much attention. Literatures showed a variety of herbal mechanisms of action used for the therapy of depression, anxiety and insomnia, involving reuptake of monoamines, affecting neuroreceptor binding and channel transporter activity, modulating neuronal communication or hypothalamic-pituitary adrenal axis (HPA) etc. Nonetheless, a systematic review on herbal pharmacology in depression, anxiety and insomnia is still lacking. This review has been performed to further identify modes of action of different herbal medicine, and thus provides useful information for the application of herbal medicine.
Topics: Animals; Anxiety; Anxiety Disorders; Depression; Depressive Disorder; Herbal Medicine; Humans; Sleep Initiation and Maintenance Disorders
PubMed: 26412068
DOI: 10.2174/1570159x1304150831122734 -
Psychopharmacology May 2016Psychosocial stressors are a well-documented risk factor for mental illness. Neuroinflammation, in particular elevated microglial activity, has been proposed to mediate... (Review)
Review
RATIONALE
Psychosocial stressors are a well-documented risk factor for mental illness. Neuroinflammation, in particular elevated microglial activity, has been proposed to mediate this association. A number of preclinical studies have investigated the effect of stress on microglial activity. However, these have not been systematically reviewed before.
OBJECTIVES
This study aims to systematically review the effects of stress on microglia, as indexed by the histological microglial marker ionised calcium binding adaptor molecule 1 (Iba-1), and consider the implications of these for the role of stress in the development of mental disorders.
METHODS
A systematic review was undertaken using pre-defined search criteria on PubMed and EMBASE. Inclusion and data extraction was agreed by two independent researchers after review of abstracts and full text.
RESULTS
Eighteen studies met the inclusion criteria. These used seven different psychosocial stressors, including chronic restraint, social isolation and repeated social defeat in gerbils, mice and/or rats. The hippocampus (11/18 studies) and prefrontal cortex (13/18 studies) were the most frequently studied areas. Within the hippocampus, increased Iba-1 levels of between 20 and 200 % were reported by all 11 studies; however, one study found this to be a duration-dependent effect. Of those examining the prefrontal cortex, ∼75 % found psychosocial stress resulted in elevated Iba-1 activity. Elevations were also consistently seen in the nucleus accumbens, and under some stress conditions in the amygdala and paraventricular nucleus.
CONCLUSIONS
There is consistent evidence that a range of psychosocial stressors lead to elevated microglial activity in the hippocampus and good evidence that this is also the case in other brain regions. These effects were seen with early-life/prenatal stress, as well as stressors in adulthood. We consider these findings in terms of the two-hit hypothesis, which proposes that early-life stress primes microglia, leading to a potentiated response to subsequent stress. The implications for understanding the pathoaetiology of mental disorders and the development of new treatments are also considered.
Topics: Animals; Humans; Inflammation; Mental Disorders; Microglia; Psychoneuroimmunology; Psychotic Disorders; Stress, Psychological
PubMed: 26847047
DOI: 10.1007/s00213-016-4218-9 -
Canadian Journal of Psychiatry. Revue... Jan 2023Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for... (Review)
Review
OBJECTIVE
Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder.
METHODS
A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria.
RESULTS
Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient.
CONCLUSIONS
There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.
Topics: Humans; Hallucinogens; Psilocybin; Depressive Disorder, Major; Canada; Anxiety; Neoplasms
PubMed: 35975555
DOI: 10.1177/07067437221111371 -
BJPsych Open Apr 2023There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. (Review)
Review
BACKGROUND
There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders.
AIMS
To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders.
METHOD
MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367.
RESULTS
The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis; diet duration: 2 weeks to 3 years; = 389; age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some individuals.
CONCLUSIONS
Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
PubMed: 37066662
DOI: 10.1192/bjo.2023.36 -
European Psychiatry : the Journal of... Dec 2021Catatonic features can appear in autism spectrum disorders (ASDs). There can be overlap in symptoms across catatonia and ASD. The overall aim of this review is to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Catatonic features can appear in autism spectrum disorders (ASDs). There can be overlap in symptoms across catatonia and ASD. The overall aim of this review is to provide evidence for the presence of catatonic features in subjects with ASD.
METHODS
A systematic literature search using the Web of Science database from inception to July 10, 2021 was conducted following PRISMA, MOOSE guidelines and the PROSPERO protocol. (CRD42021248615). Twelve studies with information about catatonia and ASD were reviewed. Data from a subset was used to conduct meta-analyses of the presence of catatonia in ASD.
RESULTS
The systematic review included 12 studies, seven of which were used for the meta-analysis, comprising 969 individuals. The mean age was 21.25 (7.5) years. Two studies (16.6%) included only children and adolescents. A total of 70-100% were males. Our meta-analysis showed that 10.4% (5.8-18.0 95%CI) of individuals with ASD have catatonia. Motor disturbances were common in ASD subjects with catatonia. No differences were found in comorbidity. Several treatments have been used in ASD with catatonic features, including benzodiazepines, antipsychotics, and electroconvulsive therapy (ECT). The findings of the systematic review showed that ECT might help manage catatonic symptoms.
CONCLUSIONS
Different features of catatonia can exist in individuals with ASD and core symptoms of catatonia are reported in ASD. Longitudinal and longer-term studies are required to understand the relationship between catatonia and ASD, and the response of catatonic symptoms to treatment.
Topics: Adolescent; Antipsychotic Agents; Autism Spectrum Disorder; Benzodiazepines; Catatonia; Electroconvulsive Therapy; Humans; Male
PubMed: 34906264
DOI: 10.1192/j.eurpsy.2021.2259 -
World Psychiatry : Official Journal of... Jun 2020Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis-orders in this age...
Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects.
Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis-orders in this age group and are used not infrequently off-label. However, the adverse effects of these medications require special attention during developmentally sensitive periods of life. For this meta-review, we systematically searched network meta-analyses and meta-analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events across 19 categories of 80 psychotropic medications - including antidepressants, antipsychotics, anti-attention-deficit/hyperactivity disorder (ADHD) medications and mood stabilizers - in children and adolescents with mental disorders. We included data from nine network meta-analyses, 39 meta-analyses, 90 individual RCTs, and eight cohort studies, including 337,686 children and adolescents. Data on ≥20% of the 78 adverse events were available for six antidepressants (sertraline, escitalopram, paroxetine, fluoxetine, venlafaxine and vilazodone), eight antipsychotics (risperidone, quetiapine, aripiprazole, lurasidone, paliperidone, ziprasidone, olanzapine and asenapine), three anti-ADHD medications (methylphenidate, atomoxetine and guanfacine), and two mood stabilizers (valproate and lithium). Among these medications with data on ≥20% of the 78 adverse events, a safer profile emerged for escitalopram and fluoxetine among antidepressants, lurasidone for antipsychotics, methylphenidate among anti-ADHD medications, and lithium among mood stabilizers. The available literature raised most concerns about the safety of venlafaxine, olanzapine, atomoxetine, guanfacine and valproate. Nausea/vomiting and discontinuation due to adverse event were most frequently associated with antidepressants; sedation, extrapyramidal side effects, and weight gain with antipsychotics; anorexia and insomnia with anti-ADHD medications; sedation and weight gain with mood stabilizers. The results of this comprehensive and updated quantitative systematic meta-review of top-tier evidence regarding the safety of antidepressants, antipsychotics, anti-ADHD medications and mood stabilizers in children and adolescents can inform clinical practice, research and treatment guidelines.
PubMed: 32394557
DOI: 10.1002/wps.20765 -
Journal of Clinical Neurology (Seoul,... Apr 2021Mental illness is disproportionately common in people with epilepsy (PWE). This systematic literature review identified original research articles that reported the... (Review)
Review
BACKGROUND AND PURPOSE
Mental illness is disproportionately common in people with epilepsy (PWE). This systematic literature review identified original research articles that reported the prevalence of psychiatric comorbidities based upon clinical assessments in a sample of PWE and assessed the clinical features of the populations found in studies included in our review of mental health comorbidity.
METHODS
The included articles were written in English and published from 2008 to 2018, and focused on adults aged ≥18 years who had psychiatric diagnoses determined in clinical assessments, such as those found in medical records, clinician psychiatric evaluations, structured diagnostic interviews, and mental health screening questionnaires specific for a psychiatric disorder. The primary outcome was the prevalence of psychiatric comorbidities as a percentage of the total sample of PWE. Additional data included the overall sample size, mean age, epilepsy type, study design, and method of diagnosis. A modified Newcastle Ottawa Scale was used to assess the quality of the studies. All 23 articles that were consistent with the inclusion criteria were related to observational studies.
RESULTS
Mood disorders and anxiety disorders were the most common psychiatric comorbidities, with prevalence rates of 35.0% and 25.6%, respectively. Major depressive disorder was the most common mood disorder, with a prevalence of 24.2%. Post-traumatic stress disorder (PTSD) had the highest reported prevalence among anxiety disorders, at 14.2%, followed by general anxiety disorder at 11.1%. Other comorbidities included psychosis (5.7%), obsessivecompulsive disorder (3.8%), schizophrenia (1.7%), bipolar disorder (6.2%), and substance abuse (7.9%). The pooled prevalence of suicidality, as reported for two studies, was 9.3%. Temporal lobe epilepsy (TLE) was associated with higher levels of psychiatric comorbidity. Two (8.7%) of the 23 studies compared psychiatric comorbidities in TLE with that of extratemporal lobe epilepsy (ETLE), and one of these two studies found that depression was more common in TLE (53.8%) than in ETLE (25%). Regarding seizure types, partial seizures were associated with a higher prevalence of depression vs generalized seizures.
CONCLUSIONS
This systematic literature review of recent original research found a relatively high prevalence of mental health comorbidities in PWE. Mood and anxiety disorders are the most common comorbidities, while psychotic spectrum conditions such as schizophrenia and bipolar disorder are much rarer. The prevalence of comorbidity may vary with the epilepsy type and treatment responsiveness. These findings suggest that screening tools for depression and anxiety should be included as part of the training for epilepsy care, while resources for other relatively common conditions such as PTSD and substance abuse disorders should be readily available to neurology specialists who treat PWE.
PubMed: 33835737
DOI: 10.3988/jcn.2021.17.2.176