ABSTRACT
Evidence from epidemiological, clinical, and biological research resulted in the immune hypothesis: the hypothesis that immune system dysfunction is involved in the pathophysiology of schizophrenia spectrum disorders (SSD). The promising implication of this hypothesis is the potential to use existing immunomodulatory treatment for innovative interventions for SSD. Here, we provide a selective historical review of important discoveries that have shaped our understanding of immune dysfunction in SSD. We first explain the basic principles of immune dysfunction, after which we travel more than a century back in time. Starting our journey with neurosyphilis-associated psychosis in the nineteenth century, we continue by evaluating the role of infections and autoimmunity in SSD and findings from assessment of immune function using new techniques, such as cytokine levels, microglia density, neuroimaging, and gene expression. Drawing from these findings, we discuss anti-inflammatory interventions for SSD, and we conclude with a look into the future.
Subject(s)
Schizophrenia , Humans , Schizophrenia/immunology , Schizophrenia/physiopathology , Neurosyphilis/immunology , Neurosyphilis/physiopathology , History, 19th Century , Immune System Diseases/immunology , Immune System Diseases/physiopathologyABSTRACT
BACKGROUND: Excessive C4A-gene expression may result in increased microglia-mediated synaptic pruning. As C4A overexpression is observed in schizophrenia spectrum disorders (SSD), this mechanism may account for the altered brain morphology (i.e. reduced volume and cortical thickness) and cognitive symptoms that characterize SSD. Therefore, this study investigates the association of C4A serum protein levels with brain morphology and cognition, and in particular whether this association differs between recent-onset SSD (n = 69) and HC (n = 40). METHODS: Serum C4A protein levels were compared between groups. Main outcomes included total gray matter volume, mean cortical thickness and cognitive performance. Regression analysis on these outcomes included C4A level, group (SSD vs. HC), and C4A*Group interactions. All statistical tests were corrected for age, sex, BMI, and antipsychotic medication dose. Follow-up analyses were performed on separate brain regions and scores on cognitive sub-tasks. RESULTS: The group difference in C4A levels was not statistically significant (p = 0.86). The main outcomes did not show a significant interaction effect (p > 0.13) or a C4A main effect (p > 0.27). Follow-up analyses revealed significant interaction effects for the left medial orbitofrontal and left frontal pole volumes (p < 0.001): C4A was negatively related to these volumes in SSD, but positively in HC. CONCLUSION: This study demonstrated that C4A was negatively related to - specifically - frontal brain volumes in SSD, but this relation was inverse for HC. The results support the hypothesis of complement-mediated brain volume reduction in SSD. The results also suggest that C4A has a differential association with brain morphology in SSD compared to HC.
Subject(s)
Schizophrenia , Humans , Schizophrenia/diagnostic imaging , Schizophrenia/complications , Complement C4a , Brain/metabolism , Gray Matter/metabolism , Cognition , Magnetic Resonance ImagingABSTRACT
Natural language processing (NLP) tools are increasingly used to quantify semantic anomalies in schizophrenia. Automatic speech recognition (ASR) technology, if robust enough, could significantly speed up the NLP research process. In this study, we assessed the performance of a state-of-the-art ASR tool and its impact on diagnostic classification accuracy based on a NLP model. We compared ASR to human transcripts quantitatively (Word Error Rate (WER)) and qualitatively by analyzing error type and position. Subsequently, we evaluated the impact of ASR on classification accuracy using semantic similarity measures. Two random forest classifiers were trained with similarity measures derived from automatic and manual transcriptions, and their performance was compared. The ASR tool had a mean WER of 30.4%. Pronouns and words in sentence-final position had the highest WERs. The classification accuracy was 76.7% (sensitivity 70%; specificity 86%) using automated transcriptions and 79.8% (sensitivity 75%; specificity 86%) for manual transcriptions. The difference in performance between the models was not significant. These findings demonstrate that using ASR for semantic analysis is associated with only a small decrease in accuracy in classifying schizophrenia, compared to manual transcripts. Thus, combining ASR technology with semantic NLP models qualifies as a robust and efficient method for diagnosing schizophrenia.
Subject(s)
Schizophrenia , Speech Perception , Humans , Semantics , Speech Recognition Software , Natural Language Processing , Schizophrenia/complications , Schizophrenia/diagnosis , SpeechABSTRACT
BACKGROUND: It has long been thought that women with a schizophrenia spectrum disorder have a more favorable course than men. However, this is not the case, even though they become ill later in life and are less likely to have comorbid drug abuse. Guidelines for prescribing antipsychotics are based on research with mostly male participants, and by following these guidelines we are doing our female patients a disservice. Gender and sex differences lead to differences in preferences, pharmacokinetics and pharmacodynamics. AIM: Providing an overview of antipsychotics for women with a schizophrenia spectrum disorder and discuss the consequences for practice. METHOD: A clinically oriented study of the literature. RESULTS: Women reach higher plasma levels than men when they receive the same dose of antipsychotic drugs (except for lurasidone and quetiapine). The effect of antipsychotics is also greater in women, because estrogens increase the brain’s dopamine sensitivity. This leads to higher risks of side effects. Clinical guidelines differ for women at different stages of life because estrogens greatly contribute to the sex differences seen in the efficacy and tolerability of antipsychotics. CONCLUSION: Clinicians should be aware that women should be treated differently with antipsychotics than men.
Subject(s)
Antipsychotic Agents , Schizophrenia , Female , Humans , Male , Antipsychotic Agents/therapeutic use , Schizophrenia/drug therapy , Quetiapine Fumarate/therapeutic useABSTRACT
BACKGROUND: Differentiating the behavioural variant of frontotemporal dementia from a depression is challenging. Recent development of automated speech analyses might add to diagnostic. AIM: To investigate the value of automated speech analyses in differentiating bvFTD from a depressive disorder. METHOD: A semistructured interview was recorded in 15 patients with bvFTD, 15 patients with a depressive disorder and 15 healthy controls, which was transcribed and analysed. Acoustic and semantic values were extracted and classified using machine learning. RESULTS: Acoustic values showed an 80% accuracy for differentiating bvFTD from depressive disorder and semantic values showed an 70.8% accuracy. CONCLUSION: Acoustic as well as semantic values show significant differences between bvFTD and depressive disorder. In automated speech analyses researches should consider privacy matters as well as possible confounders like age, sex and ethnicity. This study should be repeated in a larger population.
Subject(s)
Frontotemporal Dementia , Humans , Frontotemporal Dementia/diagnosis , Pilot Projects , Depression/diagnosis , Speech , Neuropsychological TestsABSTRACT
BACKGROUND: Currently, clinical practice lacks a usable biomarker for the detection and differentiation of depression. Such a biomarker may be found in speech, from which important information can be distilled using automated speech analysis. AIM: To provide an overview of the fast-developing field of automated speech analysis for depression. METHOD: We summarize the current literature on speech features in depression. RESULTS: Current computational models can detect depression with high accuracy, rendering them applicable for diagnostic tools based on automatic speech analysis. Such tools are developing at a fast rate. CONCLUSION: Some challenges are still in the way of clinical implementation. For example, results differ largely between studies due to much variation in methodology. Furthermore, privacy and ethical issues need to be addressed before tools can be used.
Subject(s)
Depression , Language , Humans , Depression/diagnosis , SpeechABSTRACT
BACKGROUND: Incoherent speech is a core diagnostic symptom of schizophrenia-spectrum disorders (SSD) that can be studied using semantic space models. Since linguistic connectives signal relations between words, they and their surrounding words might represent linguistic loci to detect unusual coherence in speech. Therefore, we investigated whether connectives' measures are useful to assess incoherent speech in SSD. METHODS: Connectives and their surrounding words were extracted from transcripts of spontaneous speech of 50 SSD-patients and 50 control participants. Using word2vec, two different cosine similarities were calculated: those of connectives and their surrounding words (connectives-related similarity), and those of free-of-connectives words-chunks (non-connectives similarity). Differences between groups in proportion of five types of connectives were assessed using generalized logistic models, and connectives-related similarity was analyzed through non-parametric multivariate analysis of variance. These features were evaluated in classification tasks to differentiate between groups. RESULTS: SSD-patients used less contingency (e.g., because) (p = .008) and multiclass connectives (e.g., as) (p < .001) than control participants. SSD-patients had higher minimum similarity of multiclass (adj-p = .04) and temporality connectives (e.g., after) (adj-p < .001), narrower similarity-range of expansion (e.g., and) (adj-p = .002) and multiclass connectives (adj-p = .04), and lower maximum similarity of expansion connectives (adj-p = .005). Using connectives' features alone, SSD-patients and controls could be distinguished with 85 % accuracy. DISCUSSION: Our results show that SSD-speech can be distinguished from speech of control participants with high accuracy, based solely on connectives' features. We conclude that including connectives could strengthen computational models to categorize SSD.
Subject(s)
Schizophrenia , Speech , Humans , Schizophrenia/complications , Schizophrenia/diagnosis , Linguistics , Semantics , Speech DisordersABSTRACT
BACKGROUND: Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms. METHODS: Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition. RESULTS: The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%. CONCLUSIONS: Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.
Subject(s)
Psychotic Disorders , Schizophrenia , Humans , Schizophrenia/diagnosis , Speech , Psychotic Disorders/diagnosis , Acoustics , Schizophrenic PsychologyABSTRACT
Background Women with a schizophrenia-spectrum disorder (SSD) have a better clinical profile than men at the start of their illness but lose this advantage within the first few years of living with SSD. There are benefits to be gained across different areas in the care currently offered to women with psychosis. Aim To describe point of improvement in the care for women with SSD. Method Review or relevant literature. Results An important point for improvement is the early detection of female-specific signs of a first episode of psychosis, to shorten the duration of untreated psychosis, with prompt access to early intervention services. Special attention should be paid to sexual health, and to any history of childhood trauma. Antipsychotics clearly require dosing and prescription tailored to the female body, considering hormonal life phases such as menopause. Switching to prolactin-sparing medications can benefit both mental and somatic health. Finally, hormone replacement therapy should be considered for postmenopausal women. Conclusion By providing female-specific care, women with SSD can live up to their full potential.
Subject(s)
Antipsychotic Agents , Psychotic Disorders , Schizophrenia , Antipsychotic Agents/therapeutic use , Female , Humans , Male , Prolactin , Psychotic Disorders/diagnosis , Quality Improvement , Schizophrenia/diagnosis , Schizophrenia/drug therapyABSTRACT
BACKGROUND: Auditory verbal hallucinations (AVHs) are heterogeneous regarding phenomenology and etiology. This has led to the proposal of AVHs subtypes. Distinguishing AVHs subtypes can inform AVHs neurocognitive models and also have implications for clinical practice. A scarcely studied source of heterogeneity relates to the AVHs linguistic characteristics. Therefore, in this study we investigate whether linguistic features distinguish AVHs subtypes, and whether linguistic AVH-subtypes are associated with phenomenology and voice-hearers' clinical status. METHODS: Twenty-one clinical and nineteen non-clinical voice-hearers participated in this study. Participants were instructed to repeat verbatim their AVHs just after experiencing them. AVH-repetitions were audio-recorded and transcribed. AVHs phenomenology was assessed using the Auditory Hallucinations Rating Scale of the Psychotic Symptom Rating Scales. Hierarchical clustering analyses without a priori group dichotomization were performed using quantitative measures of sixteen linguistic features to distinguish sets of AVHs. RESULTS: A two-AVHs-cluster solution best partitioned the data. AVHs-clusters significantly differed in linguistic features (p < .001); AVHs phenomenology (p < .001); and distribution of clinical voice-hearers (p < .001). The "expanded-AVHs" cluster was characterized by more determiners, more prepositions, longer utterances (all p < .01), and mainly contained non-clinical voice-hearers. The "compact-AVHs" cluster had fewer determiners and prepositions, shorter utterances (all p < .01), more negative content, higher degree of negativity (both p < .05), and predominantly came from clinical voice-hearers. DISCUSSION: Two voice-speech clusters were recognized, differing in syntactic-grammatical complexity and negative phenomenology. Our results suggest clinical voice-hearers often hear negative, "compact-voices", understandable under Broca's right hemisphere homologue and memory-based mechanisms. Conversely, non-clinical voice-hearers experience "expanded-voices", better accounted by inner speech AVHs models.
Subject(s)
Hallucinations , Voice , Hallucinations/etiology , Hallucinations/psychology , Hearing , Humans , Linguistics , SpeechABSTRACT
INTRODUCTION: Cognitive deficits are present in some, but not all patients with schizophrenia-spectrum disorders (SSD). We and others have demonstrated three cognitive clusters: cognitively intact patients, patients with deficits in a few domains and those with global cognitive deficits. This study aimed to identify cognitive subtypes of early-phase SSD with matched controls as a reference group, and evaluated cognitive subgroups regarding clinical and brain volumetric measures. METHODS: Eighty-six early-phase SSD patients were included. Hierarchical cluster analysis was conducted using global performance on the Brief Assessment of Cognition in Schizophrenia (BACS). Cognitive subgroups were subsequently related to clinical and brain volumetric measures (cortical, subcortical and cortical thickness) using ANCOVA. RESULTS: Three distinct cognitive clusters emerged: relative to controls we found one cluster of patients with preserved cognition (n = 25), one moderately impaired cluster (n = 38) and one severely impaired cluster (n = 23). Cognitive subgroups were characterized by differences in volume of the left postcentral gyrus, left middle caudal frontal gyrus and left insula, while differences in cortical thickness were predominantly found in fronto-parietal regions. No differences were demonstrated in subcortical brain volume. DISCUSSION: Current results replicate the existence of three distinct cognitive subgroups including one relatively large group with preserved cognitive function. Cognitive subgroups were characterized by differences in cortical regional brain volume and cortical thickness, suggesting associations with cortical, but not subcortical development and cognitive functioning such as attention, executive functions and speed of processing.
Subject(s)
Cognition Disorders , Cognitive Dysfunction , Schizophrenia , Brain/diagnostic imaging , Cognition , Cognition Disorders/complications , Cognition Disorders/etiology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Humans , Magnetic Resonance Imaging , Schizophrenia/complications , Schizophrenia/diagnostic imagingABSTRACT
Introduction: A strong link between voice-hearing experience and childhood trauma has been established. The aim of this study was to identify whether there were unique clusters of childhood trauma subtypes in a sample across the clinical spectrum of auditory verbal hallucinations (AVH) and to examine clinical and phenomenological features across these clusters.Methods: Combining two independent international datasets (the Netherlands and Australia), childhood trauma subtypes were examined using hierarchical cluster analysis. Clinical and phenomenological characteristics were compared across emerging clusters using MANOVA and chi-squared analyses.Results: The total sample (n = 413) included 166 clinical individuals with a psychotic disorder and AVH, 122 non-clinical individuals with AVH and 125 non-clinical individuals without AVH. Three clusters emerged: (1) low trauma (n = 299); (2) emotion-focused trauma (n = 71); (3) multi-trauma (n = 43). The three clusters differed significantly on their AVH ratings of amount of negative content, with trend-level effects for loudness, degree of negative content and degree of experienced distress. Furthermore, perceptions of voices being malevolent, benevolent and resistance towards voices differed significantly.Conclusion: The data revealed different types of childhood trauma had different relationships between clinical and phenomenological features of voice-hearing experiences. Thus, implicating different mechanistic pathways and a need for tailored treatment approaches.
Subject(s)
Adverse Childhood Experiences , Psychotic Disorders , Voice , Cluster Analysis , Hallucinations , HumansABSTRACT
INTRODUCTION: Negative content of auditory verbal hallucinations (AVH) is a strong predictor of distress and impairment. This paper quantifies emotional voice-content in order to explore both subjective (i.e. perceived) and objectively (i.e. linguistic sentiment) measured negativity and investigates associations with distress. METHODS: Clinical and non-clinical participants with frequent AVH (n = 40) repeated and recorded their AVH verbatim directly upon hearing. The AVH were analyzed for emotional valence using Pattern, a rule-based sentiment analyzer for Dutch. The AVH of the clinical individuals were compared to those of non-clinical voice-hearers on emotional valence and associated with experienced distress. RESULTS: The mean objective valence of AVH in patients was significantly more negative than those of non-clinical voice-hearers. In the clinical individuals a larger proportion of the voice-utterances was negative (34.7% versus 18.4%) in objective valence. The linguistic valence of the AVH showed a significant, strong association with the perceived negativity, amount of distress and disruption of life, but not with the intensity of distress. CONCLUSIONS: Our results indicate that AVH of patients have a more negative linguistic content than those of non-clinical voice-hearers, which is associated with the experienced distress. Thus, patients not only perceive their voices as more negative, objective analyses confirm this.
Subject(s)
Natural Language Processing , Voice , Emotions , Hallucinations/psychology , Humans , LinguisticsABSTRACT
Psychiatry is in dire need of a method to aid early detection of symptoms. Recent developments in automatic speech analysis prove promising in this regard, and open avenues for implementation of speech-based applications to detect psychiatric symptoms. The current survey was conducted to assess positions with regard to speech recordings among a group (n = 675) of individuals who experience psychiatric symptoms. Overall, respondents are open to the idea of speech recordings in light of their mental welfare. Importantly, concerns with regard to privacy were raised. Given that speech recordings are privacy sensitive, this requires special attention upon implementation of automatic speech analysis techniques. Furthermore, respondents indicated a preference for speech recordings in the presence of a clinician, as opposed to a recording made at home without the clinician present. In developing a speech marker for psychiatry, close collaboration with the intended users is essential to arrive at a truly valid and implementable method.
Subject(s)
Psychiatry , Speech , Early Diagnosis , HumansABSTRACT
Diverse lines of research testify a link, presumably causal, between immune dysregulation and the development, course and clinical outcome of psychiatric disorders. However, there is a large heterogeneity among the patients' individual immune profile and this heterogeneity prevents the development of precise diagnostic tools and the identification of therapeutic targets. The aim of this review was to delineate possible subgroups of patients on the basis of clinical dimensions, investigating whether they could lead to particular immune signatures and tailored treatments. We discuss six clinical entry points; genetic liability to immune dysregulation, childhood maltreatment, metabolic syndrome, cognitive dysfunction, negative symptoms and treatment resistance. We describe the associated immune signature and outline the effects of anti-inflammatory drugs so far. Finally, we discuss advantages of this approach, challenges and future research directions.
Subject(s)
Mental Disorders , Precision Medicine , Anti-Inflammatory Agents , Humans , Mental Disorders/diagnosisABSTRACT
Language disturbances are key aberrations in schizophrenia. Little is known about the influence of antipsychotic medication on these symptoms. Using computational language methods, this study evaluated the impact of high versus low dopamine D2 receptor (D2R) occupancy antipsychotics on language disturbances in 41 patients with schizophrenia, relative to 40 healthy controls. Patients with high versus low D2R occupancy antipsychotics differed by total number of words and type-token ratio, suggesting medication effects. Both patient groups differed from the healthy controls on percentage of time speaking and clauses per utterance, suggesting illness effects. Overall, more severe negative language disturbances (i.e. slower articulation rate, increased pausing, and shorter utterances) were seen in the patients that used high D2R occupancy antipsychotics, while less prominent disturbances were seen in low D2R occupancy patients. Language analyses successfully predicted drug type (sensitivity = 80.0%, specificity = 76.5%). Several language disturbances were more related to drug type and dose, than to other psychotic symptoms, suggesting that language disturbances may be aggravated by high D2R antipsychotics. This negative impact of high D2R occupancy drugs may have clinical implications, as impaired language production predicts functional outcome and degrades the quality of life.
ABSTRACT
Language deviations are a core symptom of schizophrenia. With the advances in computational linguistics, language can be easily assessed in exact and reproducible measures. This study investigated how language characteristics relate to schizophrenia diagnosis, symptom, severity and integrity of the white matter language tracts in patients with schizophrenia and healthy controls. Spontaneous speech was recorded and diffusion tensor imaging was performed in 26 schizophrenia patients and 22 controls. We were able to classify both groups with a sensitivity of 89% and a specificity of 82%, based on mean length of utterance and clauses per utterance. Language disturbances were associated with negative symptom severity. Computational language measures predicted language tract integrity in patients (adjusted R2 = 0.467) and controls (adjusted R2 = 0.483). Quantitative language analyses have both clinical and biological validity, offer a simple, helpful marker of both severity and underlying pathology, and provide a promising tool for schizophrenia research and clinical practice.
ABSTRACT
To test whether: (1) psychiatrists will prescribe clozapine more often if they can delegate the monitoring tasks to an advanced nurse practitioner (ANP), (2) clozapine monitoring by an ANP is at least as safe as monitoring by a psychiatrist. Patients from 23 Dutch outpatient teams were assessed for an indication for clozapine. ANPs affiliated to these teams were randomized to Condition A: clozapine monitoring by an ANP, or Condition B: monitoring by the psychiatrist. The safety of monitoring was evaluated by determining whether the weekly neutrophil measurements were performed. Staff and patients were blinded regarding the first hypothesis. Of the 173 patients with an indication for clozapine at baseline, only seven in Condition A and four in Condition B were prescribed clozapine (Odds Ratio = 2.24, 95% CI 0.61-8.21; p = 0.225). These low figures affected the power of this study. When we considered all patients who started with clozapine over the 15-month period (N = 49), the Odds Ratio was 1.90 (95% CI 0.93-3.87; p = 0.078). With regard to the safety of the monitoring of the latter group of patients, 71.2% of the required neutrophil measurements were performed in condition A and 67.3% in condition B (OR = 0.98; CI = 0.16-3.04; p = 0.98). Identifying patients with an indication for clozapine does not automatically lead to improved prescription rates, even when an ANP is available for the monitoring. Clozapine-monitoring performed by an ANP seemed as safe as that by a psychiatrist.
Subject(s)
Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Drug Monitoring , Nurse Practitioners , Professional Role , Adult , Antipsychotic Agents/administration & dosage , Clozapine/administration & dosage , Cluster Analysis , Female , Humans , Male , Middle Aged , Patient Safety , Prescriptions , Schizophrenia/drug therapyABSTRACT
BACKGROUND: Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs). METHODS: PubMed, Embase, the National Institutes of Health website (http://www.clinicaltrials.gov), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes. RESULTS: Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06-0.54], estrogens (ES: 0.78; n = 723; CI 0.36-1.19), minocycline (ES: 0.40; n = 946; CI 0.11-0.68), and NAC (ES: 1.00; n = 442; CI 0.60-1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect. CONCLUSIONS: Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Schizophrenia/drug therapy , HumansABSTRACT
BACKGROUND: Since 2017, repetitive transcranial magnetic stimulation (rTMS) has become eligible for reimbursement for the treatment of therapy-resistant depression in the Dutch healthcare system.
AIM: To initiate a guideline in the Netherlands and Belgium for the safe and effective application of rTMS for the treatment of depression.
METHOD: Based on literature review, existing guidelines and consensus among Dutch rTMS experts, recommendations were developed regarding the implementation of rTMS as a treatment of depression. All available evidence was weighed and discussed among all co-authors and recommendations were reached by consensus among the group.
RESULTS: rTMS targeting the dorsolateral prefrontal cortex (DLPFC) should be seen as a first choice in the treatment of depression using high-frequency rTMS (left) or, as an alternative, low-frequency rTMS (right). Stimulation protocols should use more than 1000 pulses per session for an average of 20-30 sessions, offered in 2-5 sessions per week. Contraindications for rTMS include epilepsy, intracranial presence of (magnetisable) metals, pacemaker and cochlear implant.
CONCLUSION: rTMS, performed by competent professionals is an effective and safe treatment for depression.