The effect of intranasal oxytocin on processing emotional stimuli during alcohol withdrawal: A randomized placebo-controlled double-blind clinical trial.

Alcohol dependence is associated with difficulties in processing emotional stimuli, which can lead to interpersonal problems. The neuropeptide oxytocin has been shown to modulate the processing of emotional stimuli, however, oxytocin treatment has not yet been examined in patients with withdrawal symptoms during alcohol detoxification. The aim of the present study was to investigate the effect of oxytocin on the reading the mind in the eyes test (RMET), which indexes theory of mind ability, during a three-day period of alcohol detoxification at an addiction treatment centre in Norway. We performed a randomized, double-blind, placebo-controlled trial in 39 patients fulfilling criteria for ICD-10 diagnosis of alcohol dependence admitted for alcohol detoxification and withdrawal treatment. Participants were randomized to receive either intranasal oxytocin (24 IU) or placebo, twice daily for three days. We evaluated RMET performance on day 2 and day 3 of detoxification and differences in RMET scores between day 2 and day 3 of detoxification. Frequentist and Bayesian statistical inference suggested that oxytocin administration during alcohol withdrawal in alcohol-dependent patients did not improve RMET performance. However, exploratory analyses provided preliminary evidence that oxytocin might improve performance on the RMET negative emotion subscale (uncorrected p value = 0.038), and that oxytocin treatment might show the most promise for those with high levels of alcohol consumption (i.e., ≥20 alcohol units per day; uncorrected p value = 0.023). Moreover, alcohol consumption levels significantly predicted RMET performance on day 2, but not on day 3, of withdrawal.

Phosphatidylethanol as Blood Biomarker of Alcohol Consumption in Early Pregnancy: An Observational Study in 4,067 Pregnant Women.

BACKGROUND: The teratogenic effects of alcohol are well documented, but there is a lack of screening methods to detect alcohol use during pregnancy. Phosphatidylethanol 16:0/18:1 (PEth) is a specific and sensitive biomarker reflecting alcohol intake up to several weeks after consumption. The aim of this study was to investigate the prevalence of positive PEth values as an indicator of early prenatal alcohol exposure in a general population of pregnant women. METHODS: Rhesus typing is routinely performed in Norway in all pregnancies around gestational week 12. Rhesus-negative women have an additional test taken around week 24. Blood samples submitted to St. Olav University Hospital in Trøndelag, Norway, for Rhesus typing during the period September 2017 to October 2018 were collected. A total of 4,533 whole blood samples from 4,067 women were analyzed for PEth (limit of quantification of 0.003 µM). RESULTS: Fifty-eight women had a positive PEth sample. Of these, 50 women were positive around gestational week 12, 3 women were positive around week 24, and in 5 cases, the timing was unknown. There were no significant differences in proportions of women with positive PEth values related to age, or rural versus urban residency. CONCLUSION: In an unselected pregnant population in Norway, 1.4% had a positive PEth sample around gestational week 12, whereas 0.4% had a positive sample around week 24. The use of PEth as an alcohol biomarker should be further investigated as a diagnostic tool in the antenatal setting.

Efficacy of Self-Administered Intranasal Oxytocin on Alcohol Use and Craving After Detoxification in Patients With Alcohol Dependence. A Double-Blind Placebo-Controlled Trial.

AIMS: The aim of this study was to assess the efficacy of self-administered intranasal oxytocin on alcohol dependence after detoxification. METHODS: In a double-blind, randomized, placebo-controlled trial, 38 patients fulfilling the criteria for ICD-10 diagnosis of alcohol dependence received either 8 IU oxytocin or placebo at their own discretion up to thrice daily for 4 weeks, after completing detoxification. Primary outcome was alcohol intake specified as the amount of alcohol consumed, the number of days to relapse into alcohol use and the proportion of subjects relapsing. Secondary outcomes were self-reported symptoms of craving, sleep and mental distress. RESULTS: There were no significant differences between the oxytocin group and the placebo group in daily alcohol intake in total (mean 1.3 ± 2.9 vs. 2.0 ± 5.0 units; P = 0.63) or on drinking days (mean 8.4 ± 2.7 vs. 7.7 ± 6.0 units; P = 0.76), in the number of days until relapse (P = 0.91) or in the proportion of subjects relapsing (37.5 vs. 41.2%; P = 0.84). Neither were there any statistically significant differences in any other outcomes, except a larger decrease in self-reported nervousness in the oxytocin group (P = 0.022). CONCLUSION: The results were inconclusive as to whether intranasal oxytocin reduced the time to relapse, degree of craving or total amount of alcohol consumed after detoxification. However, the oxytocin group had a larger decrease in self-reported nervousness.

Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin.

BACKGROUND AND AIMS: The alcohol withdrawal syndrome increases autonomic activation and stress in patients during detoxification, leading to alterations in motor activity and sleep irregularities. Intranasal oxytocin has been proposed as a possible treatment of acute alcohol withdrawal. The aim of the present study was to explore whether actigraphy could be used as a tool to register symptoms during alcohol detoxification, whether oxytocin affected actigraphy variables related to motor activity and sleep compared to placebo during detoxification, and whether actigraphy-recorded motor function during detoxification was different from that in healthy controls. METHODS: This study was a part of a randomized, double blind, placebo-controlled trial in which 40 patients with alcohol use disorder admitted for acute detoxification were included. Of these, 20 received insufflations with intranasal oxytocin and 20 received placebo. Outcomes were actigraphy-recorded motor activity during 5-hour sequences following the insufflations and a full 24-hour period, as well as actigraphy-recorded sleep. Results were related to clinical variables of alcohol intake and withdrawal, including self-reported sleep. Finally, the actigraphy results were compared to those in a group of 34 healthy individuals. RESULTS: There were no significant differences between the oxytocin group and the placebo group for any of actigraphy variables registered. Neither were there any correlations between actigraphy-recorded motor function and clinical symptoms of alcohol withdrawal, but there was a significant association between self-reported and actigraphy-recorded sleep. Compared to healthy controls, motor activity during alcohol withdrawal was lower in the evenings and showed increased variability. CONCLUSION: Intranasal oxytocin did not affect actigraphy-recorded motor activity nor sleep in patients with acute alcohol withdrawal. There were no findings indicating that actigraphy can be used to evaluate the degree of withdrawal symptoms during detoxification. However, patients undergoing acute alcohol withdrawal had a motor activity pattern different from than in healthy controls.

Effect of intranasal oxytocin on alcohol withdrawal syndrome: A randomized placebo-controlled double-blind clinical trial.

BACKGROUND: In a pilot study, intranasal oxytocin was demonstrated to reduce the benzodiazepine dose needed to relieve withdrawal symptoms during alcohol detoxification. The aim of the present study was to compare the effect of oxytocin and placebo during a three-day period of alcohol detoxification at an addiction treatment center in Norway. METHODS: Randomized, double-blind, placebo-controlled trial with 40 patients fulfilling criteria for ICD-10 diagnosis of alcohol dependence (F10.2), admitted for alcohol detoxification and withdrawal treatment. The benzodiazepine oxazepam was given as symptom-triggered treatment based on the scores of the Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) scale. Participants were randomized to receive either intranasal oxytocin (24 IU twice daily) or placebo. PRIMARY OUTCOME: Oxazepam dose required to complete a three-day course of detoxification. SECONDARY OUTCOMES: Scores of the CIWA-Ar, the 10-item Hopkins Symptom Check List (HSCL-10), and self-reported total number of hours of sleep. RESULTS: The mean total oxazepam dose (± standard deviation) was 56.8 ± 72.8 mg in the oxytocin group and 79.0 ± 122.9 in the placebo group (p = 0.490; difference -22.3 mg; 95% confidence interval (CI) -86.9 to +42.4 mg). The findings were inconclusive as to whether a difference in the CIWA-Ar score (5.94 ± 3.86 vs. 6.48 ± 3.92; p = 0.665) or in any of the other secondary outcomes was present. No serious adverse events were reported. CONCLUSION: Compared to placebo, intranasal oxytocin did not significantly reduce the oxazepam dose needed to complete a 3-day course of alcohol detoxification and withdrawal treatment.

Medication adherence in outpatients with severe mental disorders: relation between self-reports and serum level.

Medication nonadherence in severe mental disorders is an important clinical issue, but estimates vary between studies. There is a need for valid self-reports for both research and clinical practice. This study examined the level of adherence to prescribed medication in outpatients with severe mental disorders and evaluated the validity of a simple self-report rating of adherence. From an ongoing study of severe mental disorders, 280 patients with schizophrenia and bipolar disorder who were prescribed psychopharmacological agents were included. We assessed adherence with serum concentration of medicines and tested the sensitivity and specificity of a simple self-report questionnaire for patients and compared with a report from health personnel. Adherence rate defined by serum concentrations within reference level was 61.6% in the total sample, 58.4% for schizophrenia and 66.3% for bipolar disorder. The patients' self-report scores overestimated adherence, but correlated significantly to health personnel scores (r = 0.50) and to serum concentration of medication (r = 0.52); the positive predictive value was 70%, and the negative predictive value was 91%. In this naturalistic sample, outpatients with severe mental disorders showed relatively good adherence to prescribed medication, and self-report questionnaires seem to be a valid method for measuring adherence.

Adverse drug reactions of antidepressants and antipsychotics: experience, knowledge and attitudes among Norwegian psychiatrists.

Efficient prevention of adverse drug reactions (ADRs) requires knowledge about their severity and pharmacological mechanisms and is dependent on reliable data on their frequencies and possible risk factors. The study was conducted to investigate the prescribers' experience and understanding of the ADRs of psychotropic drugs, and their attitude towards reporting these. In a questionnaire, physicians treating adult psychiatric patients were asked which ADRs that they regarded bothersome for some of the most widely used antidepressants and antipsychotics. Questions about the relationship between blockade of drug receptors and ADRs, and about the physicians' personal experience of and attitudes towards reporting of ADRs were also included. In total, 70 of 91 questionnaires (78%) were returned. The mean number of ADRs regarded bothersome ranged from 2.4 to 9.3 for the various drugs/drug classes. Qualified psychiatrists stated a significantly higher number of bothersome ADRs than did the residents. The percentage of physicians associating blockade of a receptor with a specific ADR varied from 76% (histamine receptor blockade and sedation) to 37% (alpha(1)-adrenergic blockade and tachycardia). Thirty-nine per cent of the physicians had never reported an ADR to the Norwegian Medicines Agency. The number of ADRs considered bothersome was relatively high. The pattern of these ADRs generally mirrored the typical ADR profiles of the drugs. The knowledge of the underlying mechanisms of ADRs was more or less incomplete. The reporting rate of ADRs to the national regulatory authorities was low.

Prolonged pharmacokinetic drug interaction between terbinafine and amitriptyline.

Drugs with long terminal half-lives, such as terbinafine, have a potential for involvement in both long-lasting drug-drug interactions and interactions appearing weeks after discontinuation. We present a case report on a 37-year-old white woman with normal CYP2D6 metabolic capacity who was treated with amitriptyline, valproate, and olanzapine when terbinafine was introduced. Shortly thereafter she experienced extreme dryness of the mouth, nausea, and dizziness accompanied by a large increase in the serum concentrations of amitriptyline and nortriptyline. Terbinafine therapy was discontinued, and the amitriptyline dose was reduced. Surprisingly, the serum concentrations of amitriptyline and nortriptyline did not return to baseline until approximately 6 months later. Studies have shown that terbinafine is a highly potent competitive inhibitor of CYP2D6. CYP2D6 is an important intermediate enzyme in metabolism of amitriptyline to nortriptyline. Nortriptyline is further metabolized to 10-hydroxy metabolites, mainly by CYP2D6. It is, therefore, likely that the concomitant use of terbinafine was the major cause of the increased serum concentrations of amitriptyline and nortriptyline. Very different terbinafine elimination half-lives (17-400 hours) are stated in the physicians' reference guides. If the shortest estimates are used when adjusting the dose of interacting drugs, the risk of underestimating the duration of the interaction is large. Based on our data there is a risk of clinically significant drug-drug interactions for at least 3 months after stopping terbinafine intake.