RESUMO
People with substance use disorders (SUD) have a high prevalence of chronic hepatitis C virus (HCV) infection and mental health disorders. We aimed to assess the impact of integrated HCV treatment on psychological distress measured by Hopkins-symptom-checklist-10 (SCL-10). This multi-center randomized controlled trial evaluated psychological distress as a secondary outcome of integrated HCV treatment (INTRO-HCV trial). From 2017 to 2019, 289 participants were randomly assigned to receive either integrated or standard HCV treatment with direct-acting antiviral therapy. Integrated HCV treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in internal medicine outpatient clinics at centralized hospitals. Participants in the integrated treatment arm had a sustained virologic response of 93% compared to 73% for those in standard treatment arm. Psychological distress was assessed using SCL-10 prior to initiation of HCV treatment and 12 weeks after treatment completion. The mean SCL-10 score prior to HCV treatment was 2.2 (standard deviation [SD]: 0.7) for patients receiving integrated HCV treatment and 2.2 (SD: 0.8) for those receiving standard HCV treatment. Twelve weeks after the end of treatment, the mean SCL-10 score change was - 0.1 (- 0.3;0.0) in the integrated compared to the standard arm. Psychological distress did not substantially change during the treatment period and was not significantly different between the treatment arms.
Assuntos
Hepatite C Crônica , Hepatite C , Angústia Psicológica , Transtornos Relacionados ao Uso de Substâncias , Humanos , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/complicaçõesRESUMO
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT. METHODS: We used data from assessment visits of a cohort of patients in Norway. In total, 701 patients were included from May 2017 to March 2022. All patients responded at least once to two ASRS questions assessing memory and attention, respectively. Ordinal regression analyses were performed to investigate whether the two obtained scores were associated with age, sex, frequent substance use, injecting use, housing status, and educational attainment at baseline, i.e., the first assessment, and over time. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Additionally, a subsample of 225 patients completed an extended interview, including the ASRS-screener and collection of registered mental disorder diagnoses from the medical records. Standard cutoffs were used to define the presence of each ASRS symptom or a positive ASRS-screener ('ASRS-positive'). RESULTS: At baseline, 428 (61%) and 307 (53%) patients scored over the cutoffs on the 'ASRS-memory' and 'ASRS-attention,' respectively. Frequent cannabis use was associated with higher 'ASRS-memory' (OR: 1.7, 95% CI: 1.1-2.6) and 'ASRS-attention' (1.7, 1.1-2.5) scores compared with less or no use at baseline, though reduced score on the 'ASRS-memory' over time (0.7, 0.6-1.0). At baseline, frequent stimulant use (1.8, 1.0-3.2) and low educational attainment (0.1, 0.0-0.8) were associated with higher 'ASRS-memory' scores. In the subsample fulfilling the ASRS-screener, 45% of the patients were 'ASRS-positive,' of whom 13% with a registered ADHD diagnosis. CONCLUSIONS: Our findings illustrate a relationship between the ASRS-memory and -attention scores and frequent cannabis and stimulant use. Furthermore, nearly half of the subsample was 'ASRS-positive.' Patients receiving OAT might benefit from being further assessed for ADHD, but improved diagnostic methods are required.
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Transtorno do Deficit de Atenção com Hiperatividade , Cannabis , Alucinógenos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Estudos de Coortes , Noruega/epidemiologiaRESUMO
OBJECTIVES: Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use. METHODS: The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score. RESULTS: At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients. CONCLUSION: The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.
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Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Adolescente , Adulto , Olanzapina/uso terapêutico , Aripiprazol/farmacologia , Aripiprazol/uso terapêutico , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Amissulprida/farmacologia , Amissulprida/uso terapêutico , Clozapina/efeitos adversos , Risperidona/efeitos adversos , Benzodiazepinas/uso terapêutico , Piperazinas/efeitos adversos , Tiazóis/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum. METHODS: Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling. RESULTS: Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization. CONCLUSIONS: There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs.
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Antipsicóticos , Esquizofrenia , Humanos , Feminino , Adulto , Masculino , Olanzapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Aripiprazol/uso terapêutico , Amissulprida , Benzodiazepinas/efeitos adversos , Antipsicóticos/efeitos adversos , Antidepressivos/uso terapêuticoRESUMO
BACKGROUND: Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment. METHODS: This multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores. RESULTS: At baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4). CONCLUSIONS: Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906, 16/05/2017.
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Usuários de Drogas , Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Antivirais , Tratamento de Substituição de Opiáceos , Hepatite C/complicações , Fadiga , Abuso de Substâncias por Via Intravenosa/complicaçõesRESUMO
BACKGROUND: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. OBJECTIVES: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. METHODS: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016-2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. RESULTS: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: -2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (-0.50; -4.59, 3.59; 0.810). CONCLUSIONS: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.
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Metadona , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Metadona/sangue , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/genéticaRESUMO
BACKGROUND AND HYPOTHESES: Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode. STUDY DESIGN: We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button. STUDY RESULTS: We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode. CONCLUSIONS: The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the "voice" imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation.
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Alucinações , Esquizofrenia , Humanos , Esquizofrenia/complicações , Córtex Pré-Frontal , Encéfalo , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Death by suicide in patients enrolled in opioid agonist therapy (OAT) is a major clinical concern. However, little knowledge exists regarding suicide attempts in this patient group. This study presents the lifetime prevalence of suicide attempts and the associations between suicide attempts and clinical and sociodemographic variables such as education, sex, early onset of substance use (< 13 years of age), substance use patterns, and injecting substance use among patients receiving OAT. METHODS: We used data from a cohort of OAT patients in Norway obtained from a health assessment of self-reported suicide attempts and sociodemographic and clinical factors. A total of 595 patients receiving OAT were assessed from 2016 to 2020. A binary logistic regression analysis was performed and reported with an unadjusted odds ratio and 95% confidence intervals (OR). The purpose of this assessment was to analyze associations between suicide attempts and substance use patterns as well as the injection of substances during the 30 days leading up to the health assessment. A negative binomial regression analysis with an incidence rate ratio and 95% confidence intervals (IRR) was performed to investigate sex, education, early onset of substance use, and the number of suicide attempts. RESULTS: Forty-one percent of the OAT patients had attempted to die by suicide at least once during their lifetime. An early onset of substance use was strongly associated with the suicide attempts (IRR: 1.7, 1.3-2.2). No significant association was found between suicide attempts and sex (IRR: 1.2, 0.9-1.6) or education (IRR: 0.6, 0.2-2.1). Likewise, no association was identified between suicide attempts and injecting substance use (OR: 0.9, 0.6-1.3), nor using alcohol (OR: 0.9, 0.7-1.3), amphetamines (OR: 1.0, 0.7-1.3), benzodiazepines (OR: 1.0, 0.7-1.4), cannabis (OR: 1.2, 0.9-1.7), cocaine (OR: 1.3, 0.6-3.0), or opioids (OR: 1.4, 0.9-2.0). CONCLUSION: The lifetime prevalence of suicide attempts was alarmingly high in the OAT population. An early onset of substance use seemed to be an important risk factor for suicide attempts. There was a non-significant association to more current use of opioids among OAT patients with previous suicide attempts.
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Analgésicos Opioides , Transtornos Relacionados ao Uso de Substâncias , Analgésicos Opioides/efeitos adversos , Estudos Transversais , Humanos , Noruega/epidemiologia , Prevalência , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Tentativa de SuicídioRESUMO
OBJECTIVE: Akathisia is among the most unpleasant side effects related to antipsychotic drug (AP) use, and possible associations between akathisia and agitation, depression and suicidal behaviour, respectively, have been described in previous literature. New generation antipsychotics are however regarded less prone to induce this particular adverse effect compared to older drugs, but evidence is incomplete and in need of confirmation from clinically relevant samples and settings. We, therefore, aim to investigate akathisia at hospital discharge for patients consecutively admitted with acute-phase psychosis and treated with atypical antipsychotics according to guideline-concordant clinical practice. METHODS: This exploratory study is part of a naturalistic randomised controlled study in patients admitted with acute phase psychosis (N = 109). We report cross-sectional data at discharge/first follow-up after acute psychiatric hospital admission for patients with schizophrenia and related psychotic disorders. RESULTS: There were statistically significant positive associations between akathisia and the following; suicidality in men (Beta 0.306, p = 0.048), but not in women; agitation in those previously unexposed to antipsychotics (Beta 0.288, p = 0.047) and depression in those exposed to antipsychotics before hospital admittance (Beta 0.375, p = 0.031). CONCLUSION: Main findings were that akathisia is still a prevalent side effect in a clinically relevant sample of patients treated with atypical antipsychotics. Our results suggest that akathisia is significantly associated with depression, suicidality and agitation in different subgroups of patients receiving APs. Akathisia can be detrimental and the relations between akathisia and depression, suicidality and agitation should be investigated further in prospective, hypothesis-testing studies with larger samples.
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Antipsicóticos , Suicídio , Masculino , Humanos , Feminino , Antipsicóticos/efeitos adversos , Agitação Psicomotora , Ideação Suicida , Estudos Prospectivos , Estudos Transversais , DepressãoRESUMO
BACKGROUND: A potential role of inflammatory pathways in the pathology of schizophrenia has been suggested for at least a subgroup of patients. Elevated levels of the inflammatory marker C-reactive protein (CRP) have been observed, with associations to pathogenesis and symptoms. The current evidence regarding effects of antipsychotics on CRP levels is ambiguous. OBJECTIVES: To examine and compare the influence on CRP levels of three pharmacologically diverse new generation antipsychotics during a one-year follow-up in schizophrenia spectrum disorder. METHODS: In a multicenter, pragmatic and rater-blinded randomized trial, the effects of amisulpride, aripiprazole and olanzapine were compared in 128 patients with schizophrenia spectrum disorder. All had positive symptoms of psychosis at study entry. Clinical and laboratory assessments including the measurement of CRP levels were conducted at baseline, and 1, 3, 6, 12, 26, 39, and 52 weeks thereafter. RESULTS: For all antipsychotic drugs analysed together, there was an increase in CRP levels during the one-year follow-up. Aripiprazole, as opposed to amisulpride and olanzapine, was associated with a reduced CRP level after one week, after which the CRP level caught up with the other drugs. Compared to those previously exposed to antipsychotic drugs, antipsychotic-naïve patients had lower CRP levels at all follow-up time points, but with the same temporal patterns of change. CONCLUSION: Treatment with amisulpride, aripiprazole and olanzapine showed different effects on CRP levels in patients with schizophrenia spectrum disorders, modified by previous antipsychotics exposure status. This finding suggests that antipsychotic drugs may vary with respect to their influence on pro-inflammatory pathways. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01446328; URL: http://www. CLINICALTRIALS: gov/.
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Antipsicóticos , Transtornos Psicóticos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Aripiprazol/efeitos adversos , Proteína C-Reativa , Seguimentos , Humanos , Transtornos Psicóticos/tratamento farmacológicoRESUMO
OBJECTIVES: Negative emotional valence of auditory verbal hallucinations (AVHs) in schizophrenia can be a source of distress and is considered a strong predictor of illness severity. Previous studies have found glutamate to mediate AVH severity in frontal and temporal brain regions, however, they do not specifically address emotional valence of AVH. The role of glutamate for the experience of negative- versus positive emotional valence of AVH is therefore unknown and was investigated in the current study. METHODS: Using magnetic resonance spectroscopy (MRS), 37 schizophrenia patients had Glx (glutamate+glutamine) measured in the left superior temporal gyrus (STG), and additionally in the anterior cingulate cortex (ACC) and the right STG, or in the left inferior frontal gyrus (IFG). Self-reported emotional valence in AVH was measured with the Beliefs About Voices Questionnaire (BAVQ-R). RESULTS: Results from linear mixed models showed that negative emotional valence was associated with reduced Glx levels across all four measured brain regions in the frontal and temporal lobe. More specifically, voices that were experienced to be omnipotent (p = 0.04) and that the patients attempted to resist (p = 0.04) were related to lower Glx levels. Follow-up analysis of the latter showed that voices that evoked emotional resistance (i.e., fear, sadness, anger), rather than behavioral resistance, was a significant predictor of reduced glutamate (p = 0.02). CONCLUSION: The findings could indicate aberrant glutamatergic signaling, or increased NMDA-receptor hypoactivity in patients who experience their voices to be more emotionally negative. Overall, the study provides support for the glutamate hypothesis of schizophrenia.
Assuntos
Esquizofrenia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Alucinações/metabolismo , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/metabolismo , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/metabolismoRESUMO
BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, has demonstrated equal treatment outcomes, in terms of safety, opioid use, and retention, to the recommended OMT medication buprenorphine. However, premature discontinuation of XR-NTX treatment is still common and poorly understood. Research on patient experiences of XR-NTX treatment is limited. We sought to explore participants' experiences with discontinuation of treatment with XR-NTX, particularly motivation for XR-NTX, experiences of initiation and treatment, and rationale for leaving treatment. METHODS: We conducted qualitative, semi-structured interviews with participants from a clinical trial of XR-NTX. The study participants (N = 13) included seven women and six men with opioid dependence, who had received a minimum of one and maximum of four injections of XR-NTX. The study team analyzed transcribed interviews, employing thematic analysis with a critical realist approach. FINDINGS: The research team identified three themes, and we present them as a chronological narrative: theme 1: Entering treatment - I thought I knew what I was going into; theme 2: Life with XR-NTX - I had something in me that I didn't want; and theme 3: Leaving treatment - I want to go somewhere in life. Patients' unfulfilled expectations of how XR-NTX would lead to a better life were central to decisions about discontinuation, including unexpected physical, emotional, or mental reactions as well as a lack of expected effects, notably some described an opioid effect from buprenorphine. A few participants ended treatment because they had reached their treatment goal, but most expressed disappointment about not achieving this goal. Some also expressed renewed acceptance of OMT. The participants' motivation for abstinence from illegal substances generally remained. CONCLUSION: Our findings emphasize that a dynamic understanding of discontinuation of treatment is necessary to achieve a long-term approach to recovery: the field should understand discontinuation as a feature of typical treatment trajectories, and discontinuation can be followed by re-initiation of treatment.
Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Estudos Clínicos como Assunto , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Injeções Intramusculares , Masculino , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Pesquisa QualitativaRESUMO
BACKGROUND: In schizophrenia, impaired psychomotor speed is a common symptom predicting worse functional outcome. Inflammation causes changes in white matter integrity, which may lead to reduced psychomotor speed. Therefore, we wanted to investigate if peripheral inflammation assessed with cytokines affected performance on psychomotor speed in patients with a spectrum of psychotic disorders. METHODS: The current study is a prospective cohort study, including participants from a pragmatic, randomised controlled trial comparing three atypical antipsychotics in patients with a spectrum of psychotic disorders. For the purposes of this sub-study, we analysed drug treatment groups collectively. Psychomotor speed was assessed at baseline, and at weeks 6, 12, 26 and 52 of follow-up, using the neuropsychological tests trail making test (TMT) A and B, and symbol coding. Serum concentration of the following cytokines were measured: interleukin (IL)-ß, IL-2, IL-4, IL-6, IL-10, IL12 p70, IL-17a, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Blood samples were collected at baseline and after 1, 3, 6, 12, 26, 39 and 52 weeks. We analysed the effect of cytokines levels on psychomotor speed over time in linear mixed effects models. RESULTS: In our linear mixed effects models controlling for possible confounders, IFN-γ had a significant negative effect on TMT-A and symbol coding performance. None of the other tests for psychomotor speed were significantly associated with cytokines. Overall psychomotor speed performance increased significantly across the study period while cytokine levels remained stable. CONCLUSION: Our study indicates a negative association between IFN-γ and psychomotor speed, which might be of importance when understanding the mechanisms behind psychomotor deviations in psychotic disorders.
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BACKGROUND: Continuous use of amphetamines, alcohol, benzodiazepines, cannabis, cocaine, or opioids contributes to health impairments, increased morbidity, and overdose deaths among patients with substance use disorders (SUDs). This study evaluates the impact of inpatient detoxification, injecting substance use, age, and gender on substance use over time among patients undergoing outpatient SUD treatment. METHODS: We used data from a cohort of SUD patients in Norway obtained from health assessments of self-reported substance use and sociodemographic and clinical factors. A total of 881 substance use measurements, including substances and frequency of use, were assessed for 708 SUD patients in 2016-2020. Of those, 171 patients provided two or more substance use measurements. The total substance use was calculated, creating a substance use severity index (SUSI), ranging from zero (no use) to one (daily use of all substances). We defined baseline as the first substance use measurement when the measurements were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyze the SUSI at baseline and over time, and its associations with inpatient detoxification, injecting substance use, gender, and age, presented with coefficients and 95% confidence intervals (CI). RESULTS: No longitudinal changes in the SUSI were found compared with baseline (change in SUSI (cSUSI): 0.04, 95% CI: - 0.05;0.13, p = 0.397). Likewise, "inpatient detoxification" was not associated with changes in the SUSI compared with "no inpatient detoxification" (cSUSI: 0.00, 95% CI: - 0.04;0.04, p = 0.952). However, injecting substances were associated with a higher SUSI than not injecting substances at baseline (difference in SUSI: 0.19, 95% CI: 0.16;0.21, p = < 0.001), and starting to inject substances was associated with increasing SUSI over time compared with not starting to inject substances (cSUSI: 0.11, 95% CI: 0.07;0.15, p = < 0.001). Gender was not significantly associated with changes in the SUSI (cSUSI: - 0.04, 95% CI: - 0.07;0.00, p = 0.052), while patients over 60 years of age had a lower SUSI than those under the age of 30 at baseline (difference in SUSI: - 0.08, 95% CI: - 0.14;- 0.01, p = 0.018), with no change over time (cSUSI: - 0.05, 95% CI: - 0.16;0.05, p = 0.297). CONCLUSION: The present study demonstrates that inpatient detoxification was not associated with substance use changes over time for patients undergoing outpatient SUD treatment. Otherwise, injecting substance use was a particular risk factor for a high level of substance use. Future research needs to evaluate the impact of other treatment approaches on substance use, ideally in randomized controlled trials.
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Overdose de Drogas , Transtornos Relacionados ao Uso de Substâncias , Idoso , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapiaRESUMO
BACKGROUND: Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration. METHODS: All patients (n = 226, mean age 34, females 33%) diagnosed with schizophrenia spectrum disorders (SSD; F20-F29) or other psychosis (F30-F32; F10-F19), were treated with olanzapine, quetiapine, risperidone or ziprasidone, and were assessed at baseline, 4-weeks, 14-weeks, and 27-weeks. The UKU-Side Effects Self-Rating Scale version was used to evaluate the side effect profiles, and the information on substance use was based on the Clinician Drug Use Scale. RESULTS: At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia. CONCLUSION: Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.
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Transtornos Psicóticos , Transtornos Relacionados ao Uso de Substâncias , Adulto , Benzodiazepinas/efeitos adversos , Feminino , Humanos , Masculino , Olanzapina/efeitos adversos , Piperazinas , Transtornos Psicóticos/tratamento farmacológico , Fumarato de Quetiapina/efeitos adversos , Risperidona/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , TiazóisRESUMO
Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results.
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Cognitive impairment is a core aspect of psychotic disorders and difficult to treat. Atypical antipsychotics (AAs) might have differential effects on cognitive impairment, but rigid study designs and selective sampling limit the generalizability of existing findings. This pragmatic, semi-randomized, industry-independent study aimed to investigate and compare the effect of amisulpride, aripiprazole and olanzapine on cognitive performance in psychosis over a 12-month period controlling for diagnostic group. This sub study of the BeSt InTro study recruited adults with ongoing psychosis in the schizophrenia spectrum of disorders (ICD-10 diagnoses F20-F23, F25, F28 or F29; n = 104) from Bergen and Stavanger, Norway; and Innsbruck, Austria. Participants were randomized to amisulpride, aripiprazole, or olanzapine and they completed neuropsychological assessments at baseline, 6 weeks, 6 and 12 months. The test battery targeted working memory, verbal ability, and processing speed. We used Longitudinal mixed effect (LME) models to assess cognitive change for intention to treat (ITT) and per protocol (PP) medication groups, as well as comparing cognitive performance between F20 and non-F20 participants. The sample baseline global cognitive performance t-score was 42.20. Global performance improved significantly to every follow-up, including for the F20 group. There were however no significant differences in cognitive change over time between neither ITT nor PP medication groups.
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BACKGROUND: The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. METHODS AND FINDINGS: INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. CONCLUSIONS: Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906.
Assuntos
Antivirais/uso terapêutico , Prestação Integrada de Cuidados de Saúde , Usuários de Drogas , Hepatite C Crônica/tratamento farmacológico , Tratamento de Substituição de Opiáceos , Abuso de Substâncias por Via Intravenosa/reabilitação , Adulto , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/diagnóstico , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Most studies investigating antipsychotic effectiveness report either total psychopathology or symptom cluster findings. Studies focusing on a separate symptom, such as hallucinations, a hallmark symptom in schizophrenia, are scarce.Therefore, the current study aims to compare the antihallucinatory effectiveness of 3 pharmacologically different antipsychotics: olanzapine, amisulpride, and aripiprazole. METHODS: The present study is part of the Bergen-Stavanger-Innsbruck-Trondheim study, a 12-month prospective, randomized, pragmatic antipsychotic drug trial in active-phase schizophrenia spectrum disorders. The primary outcome of the present study was change of hallucinations as measured by item P3 (hallucinatory behavior) from the Positive and Negative Syndrome Scale in the subgroup with hallucinations at baseline. Primary analyses were intention to treat. RESULTS: A total of 144 participants were included in the study, where 105 (72%) had a score of 3 or more on the Positive and Negative Syndrome Scale P3 item at baseline, indicating the presence of hallucinations (HALL subgroup).In the HALL subgroup, a significantly less reduction of hallucinations was revealed for participants using olanzapine in weeks 12, 26, 39, and 52 when compared with amisulpride and in weeks 26 and 52 when compared with aripiprazole. In subanalyses for participants never exposed to antipsychotic drugs (antipsychotic-naive) and those who had used antipsychotics before entering the study, antihallucinatory differences were revealed only in the latter group. CONCLUSIONS: A differential antihallucinatory effect of the 3 study drugs was present. The inferior effect of olanzapine seems to be driven by the subgroup of participants exposed to antipsychotic treatment before entering the study.