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1.
Ned Tijdschr Geneeskd ; 1682024 May 30.
Artigo em Holandês | MEDLINE | ID: mdl-38805001

RESUMO

OBJECTIVE: To determine the prevalence of use and misuse of prescription opioids among patients at Dutch emergency departments (EDs). DESIGN: Cross-sectional multicenter study. METHOD: This study was performed at three EDs in the Nijmegen-Arnhem region. ED-patients of 18 years and older were screened for current opioid use. The Current Opioid Misuse Measure (COMM) questionnaire was used to assess opioid misuse. The presence of opioid use disorder was determined using DSM-5 based interviews. RESULTS: A total of 997 patients was screened for opioid use. The prevalence of opioid use was 15.0% (95%CI 12.9 -17.4). 22.6% (95%CI 14.6-32.4) scored positive for opioid misuse, 9.8% (95%CI 4.5-17.8) fulfilled DSM-5 criteria for opioid use disorder. CONCLUSION: Opioid use and misuse are relatively common among patients in Dutch EDs.


Assuntos
Analgésicos Opioides , Serviço Hospitalar de Emergência , Transtornos Relacionados ao Uso de Opioides , Humanos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Estudos Transversais , Masculino , Feminino , Países Baixos/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Prevalência , Adulto , Analgésicos Opioides/uso terapêutico , Inquéritos e Questionários , Pessoa de Meia-Idade
3.
J Psychopharmacol ; 38(5): 481-488, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38519421

RESUMO

OBJECTIVE: Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine. METHODS: The study was performed in 14 subjects with OUD. They received a single dose of 10mg/kg ibogaine hydrochloride. Plasma PKs of ibogaine, noribogaine, and noribogaine glucuronide were obtained during 24 h. Cytochrome P450 isoenzyme 2D6 (CYP2D6) genotyping was performed. The PKs were analyzed by means of nonlinear mixed effects modeling and related with corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity. RESULTS: The PK of ibogaine were highly variable and significantly correlated to CYP2D6 genotype (p < 0.001). The basic clearance of ibogaine (at a CYP2D6 activity score (AS) of 0) was 0.82 L/h. This increased with 30.7 L/h for every point of AS. The relation between ibogaine plasma concentrations and QTc was best described by a sigmoid Emax model. Spearman correlations were significant (p < 0.03) for ibogaine but not noribogaine with QTc (p = 0.109) and cerebellar effects (p = 0.668); neither correlated with the severity of opioid withdrawal symptoms. CONCLUSIONS: The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and/or applying individualized dosing based on CYP2D6 genotype.


Assuntos
Citocromo P-450 CYP2D6 , Genótipo , Alucinógenos , Ibogaína , Transtornos Relacionados ao Uso de Opioides , Humanos , Ibogaína/farmacocinética , Ibogaína/efeitos adversos , Ibogaína/farmacologia , Ibogaína/análogos & derivados , Masculino , Adulto , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Feminino , Alucinógenos/farmacocinética , Alucinógenos/efeitos adversos , Alucinógenos/sangue , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/genética , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/genética , Adulto Jovem , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/genética
4.
Subst Abuse Rehabil ; 15: 9-19, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510337

RESUMO

Purpose: Substance use disorder (SUD) can be a chronic relapsing condition with poor treatment outcomes. Studies exploring factors associated with abstinence or relapse after treatment are often quantitative in nature, applying linear statistical approaches, while abstinence and relapse result from non-linear, complex, dynamic and synergistic processes. This study aims to explore these underlying dynamics using qualitative comparative analysis (QCA) as a mixed methods approach to further our understanding of factors contributing to post-treatment abstinence and relapse. Patients and Methods: In a prospective study, we gathered both qualitative and quantitative data pertaining to post-treatment substance use and the factors linked to substance use outcomes. These factors encompassed psychiatric comorbidity, intellectual disability, social disintegration, post-treatment support, and engagement in activities among patients who had undergone inpatient treatment for severe SUD (n = 58). QCA, a set-theoretic approach that considers the complex interplay of multiple conditions, was applied to discern which factors were necessary or sufficient for the occurrence of either abstinence or relapse. Results: We found two solutions predicting abstinence, and five for relapse. Post-treatment conditions (support and engagement in activities) were important for retaining abstinence. For relapse, individual baseline characteristics (intellectual disability, social disintegration, psychiatric comorbidity) combined with (post-)treatment factors (post-treatment support, activities) were important. Conclusion: Although abstinence and relapse represent opposing outcomes, they each exhibit distinct dynamics. To gain a comprehensive understanding of these dynamics, it is advisable to examine them as separate outcomes. For clinical practice, it can be worthwhile to recognize that fostering the conditions conducive to abstinence may differ from preventing the factors that trigger relapse.


This study explores why some people who struggle with addiction stay clean after treatment, while others relapse. Previous studies often used traditional statistical methods, with inconclusive results due to their inability to capture the complexity of this process. To address this, we used a different approach called qualitative comparative analysis (QCA). We collected information from 58 individuals who received inpatient treatment for their addiction. We looked at different factors like mental health problems, intellectual disability, the support they got from professionals and their social network, and whether they kept themselves busy with activities. We investigated how these factors are related to staying clean or relapse. With the help of QCA, we analyzed how these factors work together to cause either drug-free living or relapse. We found that staying clean was strongly linked to getting support after treatment and being involved in activities like hobbies or work. On the other hand, relapse was more likely in people with personal problems, like intellectual disabilities and mental health problems, when support and activities were lacking after treatment. In summary, our study indicates that staying clean and relapse are different processes with different factors at play. Helping someone stay clean may therefore require different strategies than preventing relapse. This insight can guide development of more personalized healthcare for individuals dealing with addiction.

5.
Br J Gen Pract ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499298

RESUMO

INTRODUCTION: Over the past decade, long-term use of prescription opioids for chronic non-cancer pain (CNCP) has risen globally despite the associated risks. The majority of opioid users receive their first prescription in primary care. AIM: To investigate the perspective of long-term opioid users in primary care regarding the role of healthcare providers (HCP) in their prolonged opioid use. DESIGN AND SETTING: Semi-structured interviews in Dutch primary care Methods: We recruited long-term opioid users for CNCP from seven community pharmacies in the Netherlands. In-depth, semi-structured interviews focussed on experiences with long term opioid use, access to opioids, and the guidance of their HCPs. A directed content analysis was conducted on the transcribed interviews using NVivo. RESULTS: Participants (n=25) mentioned ways HCPs impacted their long-term use of opioids. These encompassed: 1) the initiation of treatment, 2) chronic use of opioids, 3) discontinuation of treatment. Participants stressed the need for risk counselling during initial prescriptions, ongoing medication evaluations including tapering conversations, and more support from their HCP during a tapering attempt. CONCLUSION: Patients' perspective illustrates the important role of HCPs across the spectrum of opioid usage - from initiation to tapering. It underscores the importance of clear risk counselling starting at the initial prescription, continuous medication assessments throughout treatment, addressing tapering at regular intervals and strong support during tapering. These insights carry significant implications for clinical practice, emphasising the importance of informed and patient-centred care when it comes to opioid use for chronic non-cancer pain management.

6.
Transl Psychiatry ; 14(1): 132, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431658

RESUMO

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = -0.32, p = 0.0023, n = 88) and remission (r = -0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Cloridrato de Venlafaxina/uso terapêutico , Depressão , Estratificação de Risco Genético , Estudo de Associação Genômica Ampla , Antidepressivos/uso terapêutico , Resultado do Tratamento
7.
Mol Psychiatry ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503923

RESUMO

Pharmacotherapy is an effective treatment modality across psychiatric disorders. Nevertheless, many patients discontinue their medication at some point. Evidence-based guidance for patients, clinicians, and policymakers on rational discontinuation strategies is vital to enable the best, personalized treatment for any given patient. Nonetheless, there is a scarcity of guidelines on discontinuation strategies. In this perspective, we therefore summarize and critically appraise the evidence on discontinuation of six major psychotropic medication classes: antidepressants, antipsychotics, benzodiazepines, mood stabilizers, opioids, and stimulants. For each medication class, a wide range of topics pertaining to each of the following questions are discussed: (1) Who can discontinue (e.g., what are risk factors for relapse?); (2) When to discontinue (e.g., after 1 year or several years of antidepressant use?); and (3) How to discontinue (e.g., what's the efficacy of dose reduction compared to full cessation and interventions to mitigate relapse risk?). We thus highlight how comparing the evidence across medication classes can identify knowledge gaps, which may pave the way for more integrated research on discontinuation.

8.
Behav Ther ; 55(2): 331-346, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418044

RESUMO

Individuals with mild intellectual disabilities or borderline intellectual functioning are at increased risk to develop a substance use disorder-however, effective treatment programs adapted to this target group are scarce. This study evaluated the effectiveness of Take it Personal!+ in individuals with mild intellectual disabilities or borderline intellectual functioning and substance use disorder. Take it Personal!+ is a personalized treatment based on motivational interviewing and cognitive-behavioral therapy supported by an mHealth application. Data were collected in a nonconcurrent multiple baseline single-case experimental design across individuals with four phases (i.e., baseline, treatment, posttreatment, and follow-up). Twelve participants were randomly allocated to baseline lengths varying between 7 and 11 days. Substance use quantity was assessed during baseline, treatment, and posttreatment with a daily survey using a mobile application. Visual analysis was supported with statistical analysis of the daily surveys by calculating three effect size measures in 10 participants (two participants were excluded from this analysis due to a compliance rate below 50%). Secondary, substance use severity was assessed with standardized questionnaires at baseline, posttreatment, and follow-up and analyzed by calculating the Reliable Change Index. Based on visual analysis of the daily surveys, 10 out of 12 participants showed a decrease in mean substance use quantity from baseline to treatment and, if posttreatment data were available, to posttreatment. Statistical analysis showed an effect of Take it Personal!+ in terms of a decrease in daily substance use in 8 of 10 participants from baseline to treatment and if posttreatment data were available, also to posttreatment. In addition, data of the standardized questionnaires showed a decrease in substance use severity in 8 of 12 participants. These results support the effectiveness of Take it Personal!+ in decreasing substance use in individuals with mild intellectual disabilities or borderline intellectual functioning.


Assuntos
Terapia Cognitivo-Comportamental , Deficiência Intelectual , Transtornos Relacionados ao Uso de Substâncias , Humanos , Deficiência Intelectual/terapia , Deficiência Intelectual/complicações , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento , Projetos de Pesquisa
9.
Psychopharmacology (Berl) ; 241(3): 613-625, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38334790

RESUMO

BACKGROUND AND PURPOSE: The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required. EXPERIMENTAL APPROACH: Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively. KEY RESULTS: All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration. CONCLUSION AND IMPLICATIONS: The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans.


Assuntos
Hidroxibutiratos , Oxibato de Sódio , Síndrome de Abstinência a Substâncias , Humanos , Ratos , Masculino , Animais , Ratos Long-Evans , Individualidade , Condicionamento Operante , Autoadministração
10.
J Eval Clin Pract ; 30(3): 473-480, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38251860

RESUMO

RATIONALE: Prescription opioid use and misuse have increased rapidly in many Western countries in the past decade. Patients (mis)using opioids are at risk of presenting to the emergency department (ED) with opioid-related problems. European data concerning prescription opioid (mis)use among the ED population is lacking. AIMS AND OBJECTIVES: This study aims to determine prevalence of prescription opioid use, misuse, and opioid use disorder (OUD) among Dutch ED patients. Secondary objectives were to explore factors associated with prescription opioid misuse and the number of patients discharged with a new opioid prescription. METHODS: In a cross-sectional multicenter study at three hospitals in the Netherlands, adult ED patients were screened for current prescription opioid use. Opioid users filled out questionnaires regarding opioid (mis)use, and underwent a structured interview to assess OUD criteria. The primary outcomes were prevalence rates of (1) current prescription opioid use, (2) prescription opioid misuse (based on a Current Opioid Misuse Measure [COMM] score > 8), (3) OUD, based on DSM-5 criteria. Independent T-tests, Pearson χ2 and Fisher's Exact tests were used to analyse differences in characteristics between groups. RESULTS: A total of 997 patients were screened, of which 15% (n = 150) used prescription opioids. Out of 93 patients assessed, 22.6% (n = 21) showed signs of prescription opioid misuse, and 9.8% (n = 9, 95% CI: 4.5-17.8) fulfilled criteria for OUD. A medical history of psychiatric disorder was significantly more common in patients with prescription opioid misuse and OUD. CONCLUSION: This study shows that prescription opioid use is relatively common in ED patients in the Netherlands, compared to the overall population. Over one fifth of these patients shows signs of opioid misuse or OUD. Awareness among ED personnel about the high prevalence of prescription opioid (mis)use in their population is critical for signalling opioid-related problems.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Uso Indevido de Medicamentos sob Prescrição , Adulto , Humanos , Analgésicos Opioides/uso terapêutico , Prevalência , Estudos Transversais , Países Baixos/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Prescrições , Serviço Hospitalar de Emergência
11.
BMJ Open ; 13(12): e075246, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070938

RESUMO

OBJECTIVES: Approximately 10% of chronic pain patients who receive opioids develop an opioid use disorder (OUD). Tapering programmes for these patients show high drop-out rates. Insight into chronic pain patients' experiences with tapering programmes for prescription OUD could help improve such programmes. Therefore, we investigated the perspectives of chronic pain patients with prescription OUD to identify facilitators and barriers to initiate and complete a specialised OUD tapering programme. DESIGN: A qualitative study using semi-structured interviews on experiences with initiation and completion of opioid tapering was audio recorded, transcribed and subject to directed content analysis. SETTING: This study was conducted in two facilities with specialised opioid tapering programmes in the Netherlands. PARTICIPANTS: Twenty-five adults with chronic pain undergoing treatment for prescription OUD participated. RESULTS: Participants indicated that tapering is a personal process, where willingness and motivation to taper, perceived (medical) support and pain coping strategies have an impact on the tapering outcome. The opportunity to join a medical-assisted tapering programme, shared decision-making regarding tapering pace, tapering location, and receiving medical and psychological support facilitated completion of an opioid tapering programme. CONCLUSIONS: According to patients, a successful treatment of prescription OUD requires a patient-centred approach that combines personal treatment goals with shared decision-making on opioid tapering. Referral to a specialised tapering programme that incorporates opioid rotation, non-judgmental attitudes, and psychological support can create a safe and supportive environment, fostering successful tapering and recovery.


Assuntos
Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Dor Crônica/tratamento farmacológico , Dor Crônica/psicologia , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Manejo da Dor , Prescrições
12.
J Clin Psychopharmacol ; 43(6): 486-492, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37930199

RESUMO

BACKGROUND: Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific. METHODS: This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks). RESULTS: EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = <0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome. CONCLUSIONS: Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.


Assuntos
Transtorno Depressivo Maior , Transtornos Psicóticos , Distúrbios do Início e da Manutenção do Sono , Humanos , Antidepressivos/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Sono , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Resultado do Tratamento , Cloridrato de Venlafaxina/uso terapêutico
13.
J Clin Med ; 12(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37762855

RESUMO

Recovery capital (RC) encompasses the wide range of resources individuals can employ to recover from Substance Use Disorder (SUD). It consists of five subdomains: human, social, cultural, financial, and community RC. Negative recovery capital (NRC) represents the obstacles to recovery. Research on (N)RC in complex multimorbid populations is scarce. This study offers an initial exploration of the viability of (N)RC in three individuals with SUD, psychiatric comorbidities, and an intellectual disability (a triple diagnosis) in inpatient addiction treatment. We collected case file data, ranked recovery goals, and conducted follow-up interviews. The data were subjected to template analysis, using (N)RC domains as codes. All domains were prevalent and relevant, showing dynamic and reciprocal effects, influenced by critical life events acting as catalysts. Notably, during treatment, patients prioritized individual skill development despite challenges in other domains. RC emerges as a valuable concept for mapping recovery barriers and facilitators in individuals with a triple diagnosis, serving as an alternative to the medical model and complementing the biopsychosocial model. It provides a systematic framework to assess critical factors for recovery in complex cases and accordingly align interventions. Future studies should explore the intersections of NRC domains and the dynamic nature of (N)RC to enhance the understanding of the challenges faced by individuals with a triple diagnosis.

14.
J Nerv Ment Dis ; 211(10): 779-783, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37557068

RESUMO

ABSTRACT: Converging evidence suggests that COVID-19 infects not only the respiratory system, but also has a large impact on the central nervous system (CNS), leading to acute neuropsychiatric symptoms (NPSs) such as anxiety and delirium. It is thus far unclear which acute NPSs are most common in COVID-19 and if NPSs are associated with an altered COVID-19 disease course. We used data from two independent retrospective cohort studies performed in an academic hospital. A total of 93 patients with NPS and 125 patients without NPS were included. Main outcome measures consisted of type of acute NPS, COVID-19 severity (based on CT severity score), admission to the intensive care unit (ICU), and mortality. Most common acute NPSs were delirium, anxiety, and mood symptoms. NPS patients were more often admitted to the ICU than patients without NPS. However, there was no difference in duration of ICU admission, CT severity score, and mortality. Somatic comorbidity was similar between the two groups. These data suggest that delirium, anxiety, and mood symptoms were the most common NPS. Independent of other clinical characteristics, ICU admission in COVID-19 patients was associated with NPS. We recommend that all COVID-19 patients should be actively screened for acute NPS such as delirium, anxiety, and mood symptoms, especially when admitted to an ICU.


Assuntos
COVID-19 , Delírio , Humanos , Estudos Retrospectivos , Estudos de Coortes , Ansiedade/epidemiologia , Ansiedade/etiologia , Unidades de Terapia Intensiva , Delírio/epidemiologia , Delírio/etiologia
15.
J Clin Med ; 12(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37445331

RESUMO

The persisting use of opioids following bariatric surgery has emerged as a prevalent complication, heightening the probability of opioid-related harm (ORM), such as opioid-related fatalities and prescription opioid use disorder (OUD). A comprehensive review of PubMed literature from 1990 to 2023 was conducted to pinpoint physiological influences on postoperative ORM. As a result, we found that patients undertaking bariatric operations often exhibit an inherently higher risk for substance use disorders, likely attributable to genetic predisposition and related neurobiological changes that engender obesity and addiction-like tendencies. Furthermore, chronic pain is a common post-bariatric surgery complaint, and the surgical type impacts opioid needs, with increased long-term opioid use after surgeries. Additionally, the subjective nature of pain perception in patients with obesity can distort pain reporting and the corresponding opioid prescription both before and after surgery. Furthermore, the postoperative alterations to the gastrointestinal structure can affect the microbiome and opioid absorption rates, resulting in fluctuating systemic exposure to orally ingested opioids. The prospect of ORM development post-bariatric surgery appears amplified due to a preexisting susceptibility to addictive habits, surgically induced pain, modified gut-brain interaction and pain management and the changed pharmacokinetics post-surgery. Further research is warranted to clarify these potential risk variables for ORM, specifically OUD, in the bariatric population.

16.
JAMA Netw Open ; 6(5): e2312443, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37155164

RESUMO

Importance: Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects. Objective: To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD). Design, Setting, and Participants: This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications. Intervention: In the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage. Main Outcomes and Measures: The primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores). Results: Of 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT. Conclusions and Relevance: In this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03548675.


Assuntos
Transtorno Depressivo Maior , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Feminino , Adulto , Masculino , Antidepressivos Tricíclicos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico , Antidepressivos/uso terapêutico , Nortriptilina/uso terapêutico , Genótipo
17.
Brain Behav ; 13(7): e3005, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37226589

RESUMO

BACKGROUND: Mindfulness-based interventions have a positive impact on pain, craving, and well-being in both patients with chronic pain and those with opioid use disorder (OUD). Although data are limited, mindfulness-based cognitive therapy (MBCT) might be a promising treatment for patients with chronic noncancer pain combined with OUD. The aim of this qualitative study was to explore the feasibility and process of change during MBCT in this particular population. METHODS: In this qualitative pilot study, 21 patients who were hospitalized for rotation to buprenorphine/naloxone as agonist treatment for chronic pain and OUD were offered MBCT. Semistructured interviews were conducted to explore experienced barriers and facilitators to MBCT. Patients who participated in MBCT were also interviewed on their perceived process of change. RESULTS: Of 21 patients invited to participate in MBCT, 12 initially expressed interest but only four eventually participated in MBCT. The timing of the intervention, group format, somatic complaints, and practical difficulties were identified as the main barriers to participation. Facilitating factors included having a positive attribution toward MBCT, an intrinsic motivation to change, and practical support. The four MBCT participants mentioned several important mechanisms of change, including reduction of opioid craving and improved coping with pain. CONCLUSIONS: MBCT offered in the current study was not feasible for the majority of patients with pain and OUD. Changing the timing of MBCT by providing it at an earlier stage of the treatment and offering MBCT in an online format may facilitate participation.


Assuntos
Dor Crônica , Terapia Cognitivo-Comportamental , Atenção Plena , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Projetos Piloto , Dor Crônica/terapia , Estudos de Viabilidade , Transtornos Relacionados ao Uso de Opioides/terapia , Resultado do Tratamento
19.
Eur Addict Res ; 29(2): 141-149, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37062280

RESUMO

INTRODUCTION: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients' perspective on developing a prescription OUD. METHODS: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. RESULTS: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. CONCLUSION: Patients' experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use.


Assuntos
Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Dor Crônica/induzido quimicamente , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Prescrições
20.
BJPsych Open ; 9(3): e74, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37078115

RESUMO

BACKGROUND: Chronic high-dose (CHD) prescription opioid use is a major public health concern. Although CHD opioid use has been associated with psychiatric disorders, the causality could go both ways. Some studies have already linked psychiatric disorders to an increased risk of transitioning to chronic opioid use, and longitudinal data identifying psychiatric disorders as predictors of CHD opioid use could shed further light on this issue. AIMS: To prospectively examine the relationship between the presence of a psychiatric disorder and subsequent development of CHD opioid use in primary care patients newly receiving opioids. METHOD: Data were included from 137 778 primary care patients in The Netherlands. Cox regression modelling was used to examine the association between psychiatric disorders prior to a new opioid prescription and subsequent CHD opioid use (≥90 days; ≥50 mg/day oral morphine equivalents) in the subsequent 2 years. RESULTS: Of all patients receiving a new opioid prescription, 2.0% developed CHD opioid use. A psychiatric disorder before the start of an opioid prescription increased the risk of CHD opioid use (adjusted hazard ratio HR = 1.74; 95% CI 1.62-1.88), specifically psychotic disorders, substance use disorders, neurocognitive disorders and multiple co-occurring psychiatric episodes. Similarly, pharmacotherapy for psychosis, substance use disorders and mood and/or anxiety disorders increased the risk of CHD opioid use. Psychiatric polypharmacy conferred the greatest risk of developing CHD opioid use. CONCLUSIONS: Psychiatric disorders increase the risk of developing CHD opioid use in patients newly receiving prescription opioids. To reduce the public health burden of CHD opioid use, careful monitoring and optimal treatment of psychiatric conditions are advised when opioid therapy is initiated.

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