Secondary Negative Symptoms Research Articles

Addressing negative symptoms of schizophrenia in a Psychosis Day Hospital: a case report

IntroductionNegative symptoms are present in more than two thirds of schizophrenic patients throughout the evolution of the disorder. These include symptoms related to reduced motivation or pleasure, such as avolition, anhedonia and asociality, and reduced expressivity, including alogia and blunted affect.We present the case of a 24-year-old man who was admitted to our Psychosis Day Hospital after several psychotic episodes, presenting with prominent negative symptomatology that was imbued with mystical delusional beliefs.Objectives1)To describe the clinical particularities of this case, focusing on the improvement of negative symptoms during the course of treatment at our Day Hospital.2)To review the available evidence regarding the pharmacological and psychotherapeutic management of negative symptoms of schizophrenia. MethodsA review of the patient’s clinical history and complementary tests were carried out. Likewise, we reviewed the available literature in relation to the management of negative symptoms of schizophrenia in an ambulatory setting.ResultsThe patient was admitted to our Day Hospital after four psychiatric hospitalizations due to mystical delusions, ideas of grandiosity and hyper-spirituality, along with prominent negative symptoms at the moment of inclusion at our centre, including social withdrawal, diminished affective response, lack of interest in the academic sphere and poor social drive. Although previous positive symptoms were present in a lesser degree, the patient interpreted the presence of the negative symptoms described above as a “punishment” or “test” from spiritual creatures.Management of negative symptoms represents a major unmet need in schizophrenia. Modest effect size evidence for pharmacological approaches favours the use of antipsychotic in monotherapy and augmentation of antipsychotic treatment with other agents, such as antidepressants. Scarce evidence regarding psychotherapeutic approaches to these symptoms points to the use of cognitive behaviour therapy and social skills training.Conclusions-Clinical identification and characterization of negative symptoms is crucial when treating patients with schizophrenia, as these are associated with important disability and poorer functional outcomes.-Differentiation of primary and secondary negative symptoms is a key aspect in the evaluation and management of schizophrenic patients.-This case outlines the coexistence of positive and negative symptoms, and illustrates the challenges in the pharmacological and psychotherapeutic management of these symptoms at a Psychosis Day Hospital.Disclosure of InterestNone Declared

The longitudinal structure of negative symptoms in treatment resistant schizophrenia

Background and hypothesisThe negative symptoms of schizophrenia are strong prognostic factors but remain poorly understood and treated. Five negative symptom domains are frequently clustered into the motivation and pleasure (MAP) and emotional expression (EE) ‘dimensions’, but whether this structure remains stable and behaves as a single entity or not remains unclear. Study designWe examined a cohort of 153 patients taking clozapine for treatment-resistant schizophrenia in a regional mental health clinic. Patients were assessed longitudinally over a mean period of 45 months using validated scales for positive, negative and mood symptoms. Network analyses were performed to identify symptom ‘communities’ and their stability over time. The influence of common causes of secondary negative symptoms as well as centrality measures were also examined. Study resultsAcross patients at baseline, two distinct communities matching the clinical domains of MAP and EE were found. These communities remained highly stable and independent over time. The communities remained stabled when considering psychosis, depression, and sedation severity, and these causes of secondary negative symptoms were clustered into the MAP community. Centrality measures also remained stable over time, with similar centrality measures across symptoms. ConclusionsOur results suggest that MAP and EE are independent dimensions that remain highly stable over time in chronic schizophrenia patients treated with clozapine. Common causes of secondary negative symptoms mapped onto the MAP dimension. Our results emphasise the need for clinical trials to address either MAP or EE, and that treating causes of secondary negative symptoms may improve MAP.

The mediating role of negative symptoms in "secondary factors" determining social functioning in chronic schizophrenia.

Chronic schizophrenia is significantly influenced by negative symptoms, with several known contributors to secondary negative symptoms. However, the impact of these factors and negative symptoms on social functioning warrants further exploration. We assessed the clinical symptoms, antipsychotic adverse reactions, and social functioning of 283 hospitalized patients with chronic schizophrenia using various standardized interviews and scales. We conducted multiple regression and mediation analyses to elucidate the impact of secondary factors on negative symptoms, and the relationship among these "secondary factors," negative symptoms, and social functioning. Our findings identified depressive symptoms, extrapyramidal symptoms, and positive symptoms as significant contributors to secondary negative symptoms. We found that negative symptoms play a notable mediating role in the effect of depressive and positive symptoms on social functioning. However, the relationship between positive symptoms, negative symptoms, and social functioning proved to be intricate. Our findings propose that negative symptoms act as pivotal mediators in the correlation between "secondary factors" (including the depressive symptoms and positive symptoms) and social functioning. The treatment of chronic schizophrenia necessitates focusing on key factors such as depressive and positive symptoms, which might significantly contribute to the development of secondary negative symptoms. Further research is essential to clarify the complex relationship among positive symptoms, negative symptoms, and social functioning in schizophrenia.

The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study

ObjectiveTo investigate the trajectories of diminished expression and apathy over 10 years. Further, to explore the effects of baseline- and persistent cannabis use on the development of diminished expression and apathy during follow-up, while controlling other potential sources and predictors of secondary negative symptoms. Methods351 participants with a first episode of non-affective psychosis were examined at baseline and invited to follow-up at one year and 10 years. The trajectories of diminished expression and apathy were investigated using linear mixed models. Subsequently, cannabis use and other potential predictors and sources of secondary negative symptoms were added to the model to investigate the respective impact on their trajectories. ResultsThe severity of both diminished expression and apathy decreased during the follow-up period after the first episode of psychosis, with the most improvement observed from baseline to 1-year follow-up. Cannabis use at baseline was associated with a long-lasting higher symptom load for diminished expression, but not apathy. Introducing persistent cannabis use to the model further strengthened the association with diminished expression. ConclusionBoth cannabis use at baseline and persistent cannabis use after a first episode of psychosis were associated with more severe symptoms of diminished expression. Our results imply a causal relationship between cannabis use and diminished expression and suggest that measures to reduce cannabis use both before and after psychosis onset may reduce expressive negative symptoms.

The efficacy of homestyle rehabilitation on negative symptoms in chronic schizophrenia: A randomized controlled trial.

Schizophrenia is a debilitating mental disorder with a high disability rate that is characterized by negative symptoms such as apathy, hyperactivity, and anhedonia that can make daily life challenging and impair social functioning. In this study, we aim to investigate the effectiveness of homestyle rehabilitation in mitigating these negative symptoms and associated factors. A randomized controlled trial was conducted to compare the efficacy of hospital rehabilitation and homestyle rehabilitation for negative symptoms in 100 individuals diagnosed with schizophrenia. The participants were divided randomly into two groups, each persisting for 3 months. The primary outcome measures were the Scale for Assessment of Negative Symptoms (SANS) and Global Assessment of Functioning (GAF). The secondary outcome measures included the Positive Symptom Assessment Scale (SAPS), Calgary Schizophrenia Depression Scale (CDSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). The trial aimed to compare the effectiveness of the two rehabilitation methods. Homestyle rehabilitation for negative symptoms was found to be more effective than hospital rehabilitation, according to the changes in SANS (T = 2.07, p = 0.04). Further analysis using multiple regression indicated that improvements in depressive symptoms (T = 6.88, p < 0.001) and involuntary motor symptoms (T = 2.75, p = 0.007) were associated with a reduction in negative symptoms. Homestyle rehabilitation may have greater potential than hospital rehabilitation in improving negative symptoms, making it an effective rehabilitation model. Further research is necessary to investigate factors such as depressive symptoms and involuntary motor symptoms, which may be associated with the improvement of negative symptoms. Additionally, more attention should be given to addressing secondary negative symptoms in rehabilitation interventions.

Primary and secondary negative symptoms severity and the use of psychiatric care resources in schizophrenia spectrum disorders: A 3-year follow-up longitudinal retrospective study

Negative symptoms represent one of the core features of schizophrenia spectrum disorders (SSD), strongly correlated with low remission rates, poor real-world functioning, and worse quality of life. Despite the body of evidence attesting the role of negative symptoms in determining worse outcomes in SSD, few studies have directly investigated their impact on the use of psychiatric services and even fewer research have examined the differential impact between primary versus secondary negative symptoms.The present study aims to investigate whether SSD subjects with high levels of primary and of secondary negative symptoms at an index hospitalization show a different use of psychiatric services in the subsequent 3 years. A total of 429 subjects were included in the study. Results show that SSD patients with high levels of negative symptoms are characterized by an overall greater use of high-cost resources, with more admissions in the hospital acute care psychiatric ward and in high intensity residential inpatient services. Moreover, while primary negative symptoms appear to play a role in determining a greater use of psychiatric services, high levels of secondary negative symptoms are associated with an increased use of most psychiatric resources, especially of high-cost ones.In conclusion, negative symptoms have a relevant impact on the pattern of psychiatric resources utilization in SSD patients. While scientific research continues to look for effective treatments for primary negative symptoms, clinicians should pay particular attention to secondary negative symptoms, as these also have important consequences but may benefit from appropriate treatment.

Factors influencing the outcome of integrated therapy approach in schizophrenia: A narrative review of the literature.

The integration of pharmacotherapy with psychosocial interventions has an important role to play in the improvement of functional outcome of subjects with schizophrenia (SCZ), in all stages of the disorder. It is essential for the adequate management of unmet therapeutic needs, such as negative symptoms and cognitive dysfunctions which account for most of the functional impairment of subjects with SCZ and do not respond to available antipsychotics. Enhancing the knowledge on factors involved in the effectiveness of integrated treatment plans is an important step forward for SCZ care. This review aims to identify factors that might influence the impact of integrated treatments on functional outcome. Most studies on the impact of psychosocial treatments on functional outcome of subjects with SCZ did not control for the effect of prescribed antipsychotics or concomitant medications. However, several factors relevant to ongoing pharmacological treatment might influence the outcome of integrated therapy, with an impact on the adherence to treatment (e.g., therapeutic alliance and polypharmacotherapy) or on illness-related factors addressed by the psychosocial interventions (e.g., cognitive dysfunctions or motivational deficits). Indirect evidence suggests that treatment integration should consider the possible detrimental effects of different antipsychotics or concomitant medications on cognitive functions, as well as on secondary negative symptoms. Cognitive dysfunctions can interfere with participation to an integrated treatment plan and can be worsened by extrapyramidal or metabolic side effects of antipsychotics, or concomitant treatment with anticholinergics or benzodiazepines. Secondary negative symptoms, due to positive symptoms, sedation, extrapyramidal side effects or untreated depression, might cause early drop-out and poor adherence to treatment. Researchers and clinicians should examine all the above-mentioned factors and implement appropriate and personalized integrated treatments to improve the outcome of SCZ.

Negative symptoms - a real unmet need

IntroductionSchizophrenia is frequently a chronic and disabling disorder, characterized by heterogeneous positive and negative symptoms. Negative symptoms are a major health concern and a core component of schizophrenia that account for a large part of the long-term disability and poor functional outcomes in patients with the disorder. Adequate treatment would mean important progress and Distinguishing primary from secondary negative symptoms may inform about treatment options.Objectives Objective: to provide information that may be useful for clinicians treating patients with negative symptoms of schizophrenia.MethodsWe searched Pubmed and Cochrane Library database for english language articles.ResultsNegative symptoms are a core component of schizophrenia that account for a large part of the long-term disability and poor functional outcomes. Negative symptoms are common in schizophrenia; up to 60% of patients may have prominent clinically relevant negative symptoms that require treatment. Negative symptoms can occur at any point in the course of illness, although they are reported as the most common first symptom of schizophrenia. Negative symptoms can be primary symptoms, which are intrinsic to the underlying pathophysiology of schizophrenia, or secondary symptoms that are related to psychiatric or medical comorbidities, adverse effects of treatment, or environmental factors. Negative symptoms clearly constitute an unmet medical need in schizophrenia, and new and effective treatments are urgently needed.ConclusionsClinically relevant negative symptoms of schizophrenia need to be recognized, assessed, and as well managed as possible in order to achieve improved outcomes for patients. More studies are needed to establish the better approach to negative symptoms.DisclosureNo significant relationships.

Striatal dopamine synthesis capacity and its association with negative symptoms upon resolution of positive symptoms in first-episode schizophrenia and delusional disorder.

How striatal dopamine synthesis capacity (DSC) contributes to the pathogenesis of negative symptoms in first-episode schizophrenia (SZ) and delusional disorder (DD) has seldom been explored. As negative symptoms during active psychotic episodes can be complicated by secondary influences, such as positive symptoms, longitudinal investigations may help to clarify the relationship between striatal DSC and negative symptoms and differentiate between primary and secondary negative symptoms. A longitudinal study was conducted to examine whether baseline striatal DSC would be related to negative symptoms at 3months in first-episode SZ and DD patients. Twenty-three first-episode age- and gender-matched patients (11 DD and 12 SZ) were consecutively recruited through an early intervention service for psychosis in Hong Kong. Among them, 19 (82.6%) patients (9 DD and 10 SZ) were followed up at 3months. All patients received an 18F-DOPA PET/MR scan at baseline. Baseline striatal DSC (Kocc;30-60) was inversely associated with negative symptoms at 3months in first-episode SZ patients (rs = - 0.80, p = 0.010). This association remained in SZ patients even when controlling for baseline negative, positive, and depressive symptoms, as well as cumulative antipsychotic dosage (β = - 0.69, p = 0.012). Such associations were not observed in first-episode DD patients. Meanwhile, the severity of negative symptoms at 3months was associated with more positive symptoms in DD patients (rs = 0.74, p = 0.010) and not in SZ patients. These findings highlight the role of striatal DSC in negative symptoms upon resolution of active psychotic episodes among first-episode SZ patients. Baseline striatal dopamine activity may inform future symptom expression with important treatment implications.

Primary and Secondary Negative Symptoms in Schizophrenia.

The negative symptoms of schizophrenia include volitional (motivational) impairment manifesting as avolition, anhedonia, social withdrawal, and emotional disorders such as alogia and affective flattening. Negative symptoms worsen patients' quality of life and functioning. From the diagnostic point of view, it is important to differentiate between primary negative symptoms, which are regarded as an integral dimension of schizophrenia, and secondary negative symptoms occurring as a result of positive symptoms, comorbid depression, side effects of antipsychotics, substance abuse, or social isolation. If secondary negative symptoms overlap with primary negative symptoms, it can create a false clinical impression of worsening deficit symptoms and disease progression, which leads to the choice of incorrect therapeutic strategy with excessive dopamine blocker loading. Different longitudinal trajectories of primary and secondary negative symptoms in different schizophrenia stages are proposed as an important additional discriminating factor. This review and position paper focuses primarily on clinical aspects of negative symptoms in schizophrenia, their definition, phenomenology, factor structure, and classification. It covers the historical and modern concepts of the paradigm of positive and negative symptoms in schizophrenia, as well as a detailed comparison of the assessment tools and psychometric tests used for the evaluation of negative symptoms.

Primary and secondary negative disorders in schizophrenia as an actual problem of modern clinical psychiatry

Negative symptoms of schizophrenia represent, at the present stage of their study, a certain group of mental pathology. They include motivation disorders or volitional disorders (anhedonia, abulia, asociality) and disorders of reduced expression or emotional disorders (alogia/poverty of speech and emotional decline/flattening). Negative symptoms are key disorders in schizophrenia, often appear at the pre-manifest stage of the disease, and significantly affect the prognosis and response to therapy. From a scientific and practical point of view, it is important to distinguish between primary and secondary negative symptoms, where the primary symptoms are nuclear, inherent in schizophrenia, and the secondary ones are the result of the influence of positive symptoms (delusions, hallucinations), depression, side-effects of medications, social isolation and hospitalism. Changes in the concept of primary and secondary negative disorders as well as a pathophysiological basis of negative symptoms are considered.

Dynamic Interplay Between Insight and Persistent Negative Symptoms in First Episode of Psychosis: A Longitudinal Study.

Persistent negative symptoms (PNS) are an important factor of first episode of psychosis (FEP) that present early on in the course of illness and have a major impact on long-term functional outcome. Lack of clinical insight is consistently associated with negative symptoms during the course of schizophrenia, yet only a few studies have explored its evolution in FEP. We sought to explore clinical insight change over a 24-month time period in relation to PNS in a large sample of FEP patients. Clinical insight was assessed in 515 FEP patients using the Scale to assess Unawareness of Mental Disorder. Data on awareness of illness, belief in response to medication, and belief in need for medication were analyzed. Patients were divided into 3 groups based on the presence of negative symptoms: idiopathic (PNS; n = 135), secondary (sPNS; n = 98), or absence (non-PNS; n = 282). Secondary PNS were those with PNS but also had clinically relevant levels of positive, depressive, or extrapyramidal symptoms. Our results revealed that insight improved during the first 2 months for all groups. Patients with PNS and sPNS displayed poorer insight across the 24-month period compared to the non-PNS group, but these 2 groups did not significantly differ. This large longitudinal study supported the strong relationship known to exist between poor insight and negative symptoms early in the course of the disorder and probes into potential factors that transcend the distinction between idiopathic and secondary negative symptoms.

Mindfulness-based group therapy for inpatients with schizophrenia spectrum disorders – feasibility, acceptability, and preliminary outcomes of a rater-blinded randomized controlled trial

IntroductionThe therapeutic effectiveness of mindfulness-based interventions (MBIs) has been shown for various mental disorders. However, for schizophrenia spectrum disorders (SSD), only a few trials have been conducted, mostly in outpatient settings.ObjectivesThis study aimed to investigate feasibility, acceptability, and preliminary effectiveness of a four-week mindfulness-based group therapy (MBGT) for in-patients with SSD.MethodsA pre-registered randomized controlled trial (RCT) was conducted at the in-patient ward for SSD. All measures were employed at baseline, post-intervention (4-weeks), and follow-up (12-weeks). The primary outcome was ‘mindfulness’. Secondary outcomes were rater-blinded positive- and negative symptoms, depression, social functioning, as well as self-rated mindfulness, depression, anxiety, psychological flexibility, quality of life, and medication regime.ResultsN=40 participants were randomized into either four-week treatment-as-usual (TAU; n=19) or MBGT+TAU (n = 21). Protocol adherence was 95.2%, and the retention rate to treatments was 95%. ANCOVA analysis revealed significant improvements in the MBGT+TAU compared to TAU for the primary outcome and negative symptoms. Exploratory analyses showed medium-to-large intervention effects on secondary outcomes mindfulness, positive, negative, and depressive symptoms, psychological flexibility, quality of life, and social functioning for MBGT+TAU and small-to-moderate changes on positive symptoms and social functioning for TAU. No serious adverse effects were reported.ConclusionsThis study supports the feasibility and acceptability of MBGT for in-patients with SSD, including high protocol adherence and retention rates. A proof of concept of the MBIs and corresponding improvements on various clinical and process parameters warrant a fully powered RCT to determine effectiveness, cost-efficiency, and longitudinal outcomes of MBGT for SSD.DisclosureNo significant relationships.

EPA guidance on treatment of negative symptoms in schizophrenia.

Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.

EPA guidance on assessment of negative symptoms in schizophrenia.

During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent. In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice. Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings. The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

Negative Symptoms of Schizophrenia: New Prospects of Cariprazine Treatment.

Cariprazine is a new piperazine derivative atypical antipsychotic, like aripiprazole and brexpiprazole. It has been approved for treating schizophrenia in many countries and has recently been included on the List of Essential Medicines in Russia. Unlike most other atypical antipsychotics, it shows high in vivo occupancy of dopamine D2 and D3 receptors at clinically relevant doses. In animal models, cariprazine has demonstrated dopamine D3 receptor-dependent pro-cognitive and anti-anhedonic effects, suggesting its potential for treating negative symptoms. This review summarizes the efficacy of cariprazine in the treatment of negative symptoms of schizophrenia. A literature search of databases covering international and Russian journals, for articles published between 1st January 2010 and 1st June 2020. Cariprazine demonstrated at least comparable efficacy in the treatment of schizophrenia symptoms to active comparators including risperidone, olanzapine or aripiprazole. The drug has a good safety profile. It appeared to be associated with a lower risk of metabolic syndromes and most extrapyramidal symptoms. The positive effect of cariprazine on the negative symptoms of schizophrenia may be associated with the elimination of secondary negative symptoms. However, of all the atypical antipsychotics to date, only cariprazine has a convincingly, methodologically robust proven advantage over risperidone in eliminating the predominant negative symptoms of schizophrenia. Yet only four studies have investigated the effect of cariprazine on the negative symptoms of schizophrenia. There is a lack of research into its direct impact on emotional-volitional disorders, anhedonia, cognitive symptoms and personality changes. However, there is evidence to suggest cariprazine is effective in treatment-resistant cases, but this requires further confirmation. Cariprazine is an effective and well-tolerated agent for the treatment of schizophrenia and may be effective in cases where other antipsychotics have failed. Cariprazine has been shown to have a positive effect on negative symptoms. Further studies are needed to collect more data on long-term treatment of schizophrenia and especially negative symptoms.

Leki przeciwpsychotyczne II generacji w terapii objawów negatywnych schizofrenii

Farmakoterapia schizofrenii jest trudnym i złożonym procesem, szczególnie w kontekście objawów negatywnych. Konieczne jest właściwe rozpoznanie grup pacjentów, a w szczególności indywidualnych pacjentów ― w zależności czy objawy negatywne są pierwotne, czy wtórne, przeważające czy znaczące, czy też przeważające i przetrwałe. Piśmiennictwo dotyczące oceny skuteczności różnych leków przeciwpsychotycznych II generacji w leczeniu objawów negatywnych jest niejednorodne, a ocena objawów negatywnych, oparta na różnych metodologiach, dotyczy przede wszystkim różnorodnych grup pacjentów, którzy najprawdopodobniej w zróżnicowany sposób reagują na badane leki, w zależności od tego, czy wykazują znaczące, przeważające lub też przeważające i przetrwałe objawy negatywne. Dodatkowo zdecydowana większość badań dotyczy ogólnej populacji chorych na schizofrenię, wśród których oceniano między innymi nasilenie objawów negatywnych. W związku z tym ocena tych badań i ich porównanie między sobą jest praktycznie niemożliwe. Wybór leku przeciwpsychotycznego II generacji, który wykazywałby zdecydowaną przewagę nad innymi, jest również trudny. W ramach niniejszego opracowania wykonano przegląd literatury dotyczącej badań randomizowanych bezpośrednio porównujących kluczowe leki przeciwpsychotyczne II generacji stosowane w terapii objawów negatywnych. W większości analizowanych badań nie wykazano istotnych statystycznie różnic pomiędzy analizowanymi lekami (porównanie risperidonu, amisulprydu, arypiprazolu, olanzapiny pomiędzy sobą). Tylko w pojedynczych badaniach wykazano przewagę olanzapiny nad risperidonem w ocenie wpływu obu tych leków na objawy negatywne. Należy jednak podkreślić, że wyniki cechowały się ograniczoną wiarygodnością w zakresie możliwości wnioskowania o bezpośrednim wpływie leków na objawy negatywne. Przyczynę takiego stanu rzeczy należy upatrywać między innymi w tym, że w badaniach tych nie korygowano uzyskiwanych efektów o czynniki zakłócające, których wpływ na objawy negatywne został potwierdzony. Natomiast w grupie chorych z przeważającymi i przetrwałymi objawami negatywnymi stwierdza się przewagę kariprazyny nad risperidonem. Uzupełniająca analiza opracowań wtórnych dla analizowanych leków wykazała wyższą skuteczność leków II generacji nad lekami I generacji i placebo w różnych grupach pacjentów z objawami negatywnymi. Należy jednak podkreślić, że badania ze względu na swoją niejednorodność są trudne do porównania. Dodatkowym problemem, który pojawia się w kontekście badań klinicznych, a także codziennej praktyki, jest właściwa diagnoza i odróżnienie pierwotnych objawów negatywnych od wtórnych objawów negatywnych.

Exploring the Effects of an Acute Dose of Antipsychotic Medication on Motivation-mediated BOLD Activity Using fMRI and a Perceptual Decision-making Task

The left inferior frontal gyrus and the bilateral ventral striatum are thought to be involved in motivation-mediated decision-making. Antipsychotics may influence this relationship, and atypical antipsychotics improve secondary negative symptoms in schizophrenia, such as loss of motivation, although the acute effects of pharmacological medication on motivation are not fully understood. In this single-blinded, randomized controlled trial, 49 healthy volunteers were randomized into three groups to receive a single dose of haloperidol, aripiprazole or placebo. Between 4.0 and 5.6 h later, participant’s brain blood-oxygen-level dependent (BOLD) activity was recorded using functional magnetic resonance imaging (fMRI) while completing a perceptual decision-making fMRI task consisting of one neutral and one motivated condition. Response bias, reflecting the participant’s willingness to say that the target stimulus is present, was calculated using signal detection theory. Concurrent with widespread changes in BOLD signal in the motivated vs. neutral condition, a less conservative, mathematically optimal response bias was observed in the motivated condition across the whole sample. Within-group differences in BOLD signal in the left inferior frontal gyrus and bilateral ventral striatum were observed between conditions in the aripiprazole and haloperidol groups, but not in the placebo group. No robust between-group differences in brain activity in the left inferior frontal gyrus or the bilateral ventral striatum were found. Overall, we found no robust evidence for an effect of either aripiprazole or haloperidol on motivationally mediated behavior. An interesting pattern of correlations possibly related to pharmacologically induced alterations in the dopamine system was observed, although findings remain inconclusive and must be replicated in larger samples.

Using Patient-Centered Assessment in Schizophrenia Care: Defining Recovery and Discussing Concerns and Preferences.

Syndromal recovery, satisfactory quality of life, and adequate functionality are relevant goals that define successful treatment of schizophrenia. Recovery requires effective symptom control in multiple clinical domains but also sufficient self-care and social and educational/vocational functionality. The finding that residual negative and cognitive symptoms have been related strongly to inadequate levels of functioning in people with schizophrenia is related to the fact that current pharmacologic agents tend to be most effective for the positive symptoms of the disease. Additional challenges include psychiatric comorbidities and adverse events related to medication that can lead to secondary negative and cognitive symptoms and nonadherence, all of which can worsen outcomes. Treatment modalities that target cognition and functional rehabilitation without introducing tolerability issues are needed. In general, pharmacologic interventions should be combined with evidence-based nonpharmacologic treatments, and patient-reported outcomes as well as measurement-based care should be employed, ideally in a coordinated specialty care framework. To facilitate positive treatment decisions, a combined shared decision and motivational interviewing approach should be implemented.

Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment.

Schizophrenia is frequently a chronic and disabling disorder, characterized by heterogeneous positive and negative symptom constellations. The objective of this review was to provide information that may be useful for clinicians treating patients with negative symptoms of schizophrenia. Negative symptoms are a core component of schizophrenia that account for a large part of the long-term disability and poor functional outcomes in patients with the disorder. The term negative symptoms describes a lessening or absence of normal behaviors and functions related to motivation and interest, or verbal/emotional expression. The negative symptom domain consists of five key constructs: blunted affect, alogia (reduction in quantity of words spoken), avolition (reduced goal-directed activity due to decreased motivation), asociality, and anhedonia (reduced experience of pleasure). Negative symptoms are common in schizophrenia; up to 60% of patients may have prominent clinically relevant negative symptoms that require treatment. Negative symptoms can occur at any point in the course of illness, although they are reported as the most common first symptom of schizophrenia. Negative symptoms can be primary symptoms, which are intrinsic to the underlying pathophysiology of schizophrenia, or secondary symptoms that are related to psychiatric or medical comorbidities, adverse effects of treatment, or environmental factors. While secondary negative symptoms can improve as a consequence of treatment to improve symptoms in other domains (ie, positive symptoms, depressive symptoms or extrapyramidal symptoms), primary negative symptoms generally do not respond well to currently available antipsychotic treatment with dopamine D2 antagonists or partial D2 agonists. Since some patients may lack insight about the presence of negative symptoms, these are generally not the reason that patients seek clinical care, and clinicians should be especially vigilant for their presence. Negative symptoms clearly constitute an unmet medical need in schizophrenia, and new and effective treatments are urgently needed.