Enablers and hindrances for longer-term abstinence in opioid dependent individuals receiving treatment with extended-release naltrexone: A Norwegian longitudinal recovery trial (NaltRec study).

Opioid-dependence is a comprehensive, relapsing disorder with negative individual, - family, - and societal consequences. Recovery is difficult to achieve. Research has shown reduced substance use and improved health- and psychosocial factors with extended-release naltrexone (XR-NTX) treatment. Pharmacological treatment should include psychosocial interventions to improve longer-term recovery. This study explores how voluntary monthly treatment with extended-release naltrexone hydrochloride (Vivitrol®) will influence longer-term recovery, health and psychosocial relationships in opioid-dependent patients. Close relatives' experiences and societal costs will be assessed. This Norwegian naturalistic, multicenter, open-label study includes 150 opioiddependent patients. Patients are assessed every four weeks for 24 weeks, with 28 weeks optional follow-up treatment-period, and at three, six and 12 months posttreatment. Controls are opioid-dependent patients enrolled in Opioid Maintenance Treatment programs (n = 150). Data on recovery will be collected from participants, close relatives, and community health service providers. Genetic analyses of major signaling pathways and national registries on prescriptions and health care use will be analyzed. Recruitment period is September 2018 to September 2020. The assessment of medical, psychological, relational and societal factors may provide novel in-depth knowledge on the complexity of personal recovery-processes. The results are expected to have impact on priorities in treatment and follow-up for opioid dependent patients.

Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs.

BACKGROUND: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals. METHODS: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions. DISCUSSION: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.

Delayed pressure urticaria treated with the selective serotonin reuptake inhibitor escitalopram.

There is increasing evidence of platelet activation and systemic inflammation in chronic spontaneous urticaria and delayed pressure urticaria (DPU). Inflammation may be central to understanding the high comorbidity of depression and anxiety in patients with chronic urticaria (CU). We report a case of DPU and depression in a patient, which responded favourably to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram. Sustained administration of SSRIs is associated with downregulation of serotonin transporters/receptors and depletion of platelet stored serotonin, which may reduce the ability of platelets to aggregate after thrombotic triggers. SSRIs are easier to manage and have significantly less disturbing adverse effects and cardiotoxicity than the tricyclic antidepressants (TCAs). SSRIs may represent an alternative to the traditional use of TCAs in treatment of CU.

Changes in cognitive function during psychogeriatric treatment in relation to benzodiazepine cessation.

INTRODUCTION: The aim of this study was to investigate cognitive functions after admission to a geriatric psychiatric hospital, and to study the short-term effects of cessation of benzodiazepine use on cognitive functions. METHODS: Details of benzodiazepine use and serum concentration measurements were recorded on admission. The Hopkins verbal learning test, the Stroop test, Digit Vigilance Test and the Mini Mental Status Examination were performed on admission, and after 4 weeks of hospitalization. Test results were compared for the total group of patients, as well as for benzodiazepine "continuers" and the "quitters". RESULTS: For all patients (n=224), improved performances were observed in 10 out of 12 cognitive tests. Significant improvements were seen in 4 out of 12 tests. Benzodiazepine "quitters" improved significantly more than the "continuers" (p=0.027) only on the Hopkins verbal learning test, delayed recall performance. DISCUSSION: Among elderly psychiatric patients, cognitive function improved slightly during the 4 weeks of hospital treatment, but only for one of the memory tests, the improvement was related to the cessation of benzodiazepine treatment.

A clinical study of the cognitive effects of benzodiazepines in psychogeriatric patients.

Previous studies have shown cognitive impairment in long-term benzodiazepine users compared to non-users. However, little is known about such effects in a population of geriatric psychiatry patients. The aim of this study was to identify differences between benzodiazepine users and non-users on standardized tests of the cognitive fields of learning and memory, executive functions and vigilance, at admittance to a department of geriatric psychiatry.Hopkins verbal learning test, Stroop test and digit vigilance test were performed in all patients. Test performances were compared between benzodiazepine users (n=168) and non-users (n=73). A multiple linear regression model was used, adjusting for different baseline characteristics (years of education, dementia and depression).No significant differences in test results were found between benzodiazepine users and non-users on 11 out of 12 cognitive tests results. On one of the 12 test results (time used on the digit vigilance test), benzodiazepine users showed better performance compared to non-users (ß=-0.20, p=0.032). This finding was not statistically significant after Bonferroni correction for multiple testing.This study of geriatric psychiatry benzodiazepine users did not reveal cognitive impairment compared to non-users on the cognitive areas tested. Other possible negative consequences of benzodiazepine use should, however, also be considered when prescribing drugs to older patients.

Serum concentrations of citalopram--dose-dependent variation in R- and S-enantiomer ratios.

INTRODUCTION: The antidepressive effect of racemic citalopram (CIT) is exerted by S-CIT, while R-CIT is a partial antagonist to S-CIT. Since R-and S-CIT are metabolized by different pathways, we investigated whether the ratio of S- and R-CIT may differ between individuals on the same dose of racemic CIT, and if a possible variability in the R/S-ratio could be dose-dependent. METHODS: A chiral analysis of R- and S-CIT in serum samples taken from 88 female patients receiving treatment with racemic CIT was performed using high-pressure liquid chromatography. RESULTS: The mean levels of R-CIT were significantly higher than those of S-CIT in all dose groups. The R/S-CIT ratio increased from 1.99 to 2.45 with an increase in the dose (p<0.05), and the interindividual variance in the R/S-CIT ratio was up to four-fold on the same dosage. DISCUSSION: Our findings show that the stereoselective metabolism of citalopram IN VIVO has pharmacokinetic consequences reflected by dose dependent variations of enantiomeric drug concentrations, as well as substantial interindividual variabilities in the ratios of the concentrations. The clinical consequences, however, are unclear and should be further explored.

Serum concentrations of risperidone and 9-OH risperidone following intramuscular injection of long-acting risperidone compared with oral risperidone medication.

OBJECTIVE: To compare serum concentrations of risperidone, 9-hydroxy (OH) risperidone and risperidone plus 9-OH risperidone, as well as the 9-OH risperidone/risperidone ratio in patients receiving depot and oral risperidone. METHOD: Serum concentrations from 78 patients receiving three different doses of risperidone depot were measured and compared with serum concentrations from 82 patients taking three different doses of oral risperidone. RESULTS: Patients receiving risperidone depot had significantly lower serum concentrations of risperidone plus 9-OH risperidone than patients taking oral risperidone. More interestingly, the 9-OH risperidone/risperidone ratio was also significantly lower in patients receiving risperidone depot than in patients taking oral risperidone. CONCLUSION: Serum concentrations of risperidone plus 9-OH risperidone may be a rather poor indication of the antipsychotic efficacy of risperidone unless their ratio is also considered.

Personality and physical symptoms in nonpsychiatric patients with functional gastrointestinal disorder.

OBJECTIVE: We investigated the relationship between personality and reported pain and somatic distress in patients with functional gastrointestinal disorder (FGD) without psychopathology. METHODS: Fifty-six patients and 55 controls completed Buss-Durkee Hostility Inventory (BDHI), NEO Personality Inventory (NEO-PI), Eysenck Personality Questionnaire (EPQ: N+L scales), and Giessener Physical Complaints Checklist (GBB). Patients also completed McGill Pain Questionnaire (MPQ) and Visual Analogue Scale (VAS) for abdominal pain and target symptom (abdominal distress). RESULTS: Patients displayed significantly higher levels of neuroticism and covert aggression than controls. Number of words chosen (NWC) to describe pain and sensory pain index (MPQ), but not pain intensity on VAS, were predicted by indirect aggression -- and less so by neuroticism -- in females and covert aggression in males (stepwise regression model). Patients reported far more extraintestinal somatic complaints than controls. CONCLUSION: Out of nine dimensions of hostility and five dimensions of personality, only neuroticism and concealed aggression are increased in FGD patients without psychiatric comorbidity compared with healthy controls. These personality traits influence pain reports and should be taken into account when evaluating and treating patients with FGD. Neuroticism and concealed aggression are most likely markers of vulnerability to FGD and not merely reflections of being chronic ill or explained by sample bias secondary to illness behavior.

Personality traits predict treatment outcome with an antidepressant in patients with functional gastrointestinal disorder.

BACKGROUND: We investigated the relationship between personality traits and response to treatment with the tetracyclic antidepressant mianserin or placebo in patients with functional gastrointestinal disorder (FGD) without psychopathology. METHODS: Forty-eight patients completed the Buss-Durkee Hostility Inventory, Neuroticism Extroversion Openness -Personality Inventory (NEO-PI), and Eysenck Personality Questionnaire (EPQ), neuroticism + lie subscales, before they were consecutively allocated to a 7-week double-blind treatment study with mianserin or placebo. Treatment response to pain and target symptoms were recorded daily with the Visual Analogue Scale and Clinical Global Improvement Scale at every visit. RESULTS: A low level of neuroticism and little concealed aggressiveness predicted treatment outcome with the antidepressant drug mianserin in non-psychiatric patients with FGD. Inversely, moderate to high neuroticism and marked concealed aggressiveness predicted poor response to treatment. These findings were most prominent in women. Personality traits were better predictors of treatment outcome than serotonergic sensitivity assessed with the fenfluramine test. CONCLUSION: Assessment of the personality traits negativism, irritability, aggression, and neuroticism may predict response to drug treatment of FGD even when serotonergic sensitivity is controlled for. If confirmed in future studies, the findings point towards a more differential psychopharmacologic treatment of FGD.

Reboxetine: tolerability and safety profile in patients with major depression.

Since reboxetine acts selectively on the reuptake of noradrenaline, it has a different side-effects profile than drugs acting predominantly on the serotonin reuptake mechanism. Data from patients treated with reboxetine (n = 1503) or placebo/comparator drugs (n = 1027) show that reboxetine has no significant cardiovascular effects, a low potential for drug interactions, causes no significant impairment of cognitive or motor function and no increase in suicidal ideation. In contrast to certain serotonergic drugs, there is no evidence of any withdrawal syndrome upon abrupt discontinuation or tapering of reboxetine treatment. Sexual dysfunction appears in only a small fraction of the patients and mainly with doses higher than 8 mg daily. The rate of discontinuation due to adverse effects with reboxetine was not significantly different from that observed with placebo in short-term studies. The level of efficacy and apparently favourable tolerability profile makes reboxetine an important alternative in the medical treatment of depressive illness.

Fenfluramine challenge test predicts outcome in pharmacological treatment of patients with functional gastrointestinal disorder.

We investigated if response to the fenfluramine challenge test could predict outcome in 47 nonpsychiatric patients with chronic functional gastrointestinal disorder (FGD) treated with mianserin, a drug closely related to mirtazepine, or placebo. Sixty milligrams of fenfluramine was given orally in the morning on nonfasting basis. Serum cortisol (COR) and prolactin (PRL) were analyzed at baseline, and after 120, 180, and 240 minutes. Patients were then randomized into a 7-week double-blind treatment trial with mianserin or placebo. Response to treatment with mianserin (76% vs.18% for placebo) was closely linked to a high increase in PRL and COR following a fenfluramine challenge test (positive predictive power=72%). Adding length of illness history increased both positive and negative predictive power to 92%. Our results indicate that the fenfluramine challenge test may be a potentially useful tool to identify nonpsychiatric subjects with FGD, who will most likely respond to treatment with a combined alpha2 and 5HT-2 and -3 antagonist.

Fenfluramine and idiopathic pain: a serotonergic study in non-psychiatric patients with functional gastrointestinal disorder.

BACKGROUND: We investigated prolactin and cortisol response to fenfluramine in non-psychiatric patients with chronic functional gastrointestinal disorder (FGD). METHODS: Sixty milligrams fenfluramine was given orally to 55 subjects without any DSM-III axis-1 psychopathology and 29 healthy control subjects matched for sex and age. Serum cortisol and prolactin levels were analysed at base line and after 120, 180, and 240 min. RESULTS: Fenfluramine challenge induced an increase in mean prolactin and cortisol serum values in both patients and controls. Female patients showed lower base-line values of prolactin and higher delta values of cortisol than controls. Male patients and controls showed very uniform values for all variables. Length of illness history influenced delta cortisol values in both sexes. CONCLUSIONS: The cortisol and prolactin responses to fenfluramine suggest a psychobiologic gender difference with a possible stress-induced central serotonergic dysfunction in female patients but not in male patients. The close relationship between length of illness and delta cortisol may also suggest an increased state of distress in females with chronic functional gastrointestinal disorder.

A new pharmacologic treatment of functional gastrointestinal disorder. A double-blind placebo-controlled study with mianserin.

BACKGROUND: The efficacy of unselected monoamine reuptake inhibitors (tricyclic antidepressants) in the treatment of patients with functional gastrointestinal disorders (FGD) has not been convincingly demonstrated. We investigated the efficacy of an antidepressant (mianserin) with a different receptor profile (combined 5-hydroxytryptamine-2 + 3 and alpha-2 antagonist) in FGD. METHODS: After excluding patients with psychopathology and initial placebo responders from the study, eligible patients (n = 49) were randomized to 7 weeks of double-blind treatment with either mianserin, 120 mg/day, or placebo. Efficacy was assessed by using observer-completed ratings, the Global Improvement Scale, and patient self-ratings, Visual Analog Scale, and Disability Scales. RESULTS: Patients taking mianserin reported less abdominal pain, symptoms of abdominal distress, and functional disability than those given placebo (p < 0.001). The efficacy was significant across different lengths of illness periods and types of functional disorder. There was no major change 4 weeks after tapering. CONCLUSION: Mianserin may be an effective and well-tolerated pharmacologic short-term treatment for functional gastrointestinal disorders in patients with no clinical evidence of psychopathology.