Social educator students' readiness to address sexual health in their future profession.

BACKGROUND: Norwegian social educator students' attitudes towards addressing sexual health are unknown, even if their future clients often have needs related to sexual issues. PURPOSE: To investigate social educator students' readiness to address sexual health in their future profession. METHODS: In 2019, 213 social educator students (response rate 34%) responded to the Students' Attitudes towards addressing Sexual Health Extended online questionnaire. RESULTS: Most of the social educator students felt comfortable and ready to address sexual health in their future profession, but thought they had insufficient competence and education concerning sexual health. There were gender and age differences when discussing sexual health among persons with intellectual disabilities. CONCLUSION: Despite most Norwegian social educator students feeling ready to address sexual health, they needed additional competences and education. Further research is needed concerning the effectiveness of educational interventions targeting competence in sexual health, to ensure sufficient support for clients in this field.

Substantial Differences in Serum Concentrations of Psychoactive Drugs Measured in Samples Stored for 2 Days or More on Standard Serum Tubes Versus Serum Tubes Containing Gel Separators.

BACKGROUND: Drugs may potentially adsorb to blood collection tubes containing gel separators in the preanalytical phase of therapeutic drug monitoring. The aim of this study was to compare measured concentrations of 28 psychoactive drugs and 13 metabolites in spiked serum samples stored on standard (plain) tubes versus barrier gel tubes during a 2-6-day period at room temperature. METHODS: Drug-free ("blank") serum samples spiked with mixes of antidepressants, antipsychotics, or mood stabilizers (valproic acid and lamotrigine), including relevant metabolites, were transferred to tubes with and without gel, that is, BD Vacutainer SST II Advance gel tubes and BD Vacutainer Glass Serum Tubes (Becton-Dickinson Company, Plymouth, United Kingdom). Mean serum concentrations of the drugs or metabolites measured by ultra-high performance liquid chromatography-tandem mass spectrometry analyses of protein-precipitated samples were compared after storage on plain or gel tubes at 3 time points (day 0, day 2/48 hours, and day 6/144 hours) in room temperature. RESULTS: Mean serum concentrations of all antidepressants, except for one metabolite, and 13 of 18 antipsychotic drugs were significantly lower in gel tubes compared with plain tubes after 2 days of storage (2%-28% lower, P < 0.05). After 6 days of storage, mean serum concentrations of all antipsychotic drugs and antidepressants were significantly lower in gel tubes versus plain tubes (9%-49% lower, P < 0.02), except for amisulpride and O-desmethylvenlafaxine. Serum concentrations of the mood stabilizers were not significantly different in gel tubes compared with plain tubes (P > 0.1). There was a clear relationship between log P (partition coefficient) and residual serum concentrations during gel tube storage (r -0.50 and -0.42 at day 2 and day 6, respectively; P < 0.02). CONCLUSIONS: This study shows that storage on gel for more than 2 days significantly decreases the serum concentrations of antidepressant and antipsychotic drugs as compared to storage in plain tubes. Thus, using tubes with gel separators in the therapeutic drug monitoring of psychoactive drugs should be reconsidered.

Valproic Acid significantly lowers serum concentrations of olanzapine-an interaction effect comparable with smoking.

BACKGROUND: Preliminary reports have indicated that valproic acid (VPA) reduces serum concentrations of olanzapine (OLZ). The aim of this study was to investigate the impact of VPA and other antiepileptic drugs (AEDs) on serum concentrations of OLZ and 3 of its major metabolites in a large-scale material of therapeutic drug monitoring samples. METHODS: OLZ-treated patients were stratified into subgroups according to coadministration of various AEDs, that is, lamotrigine (LTG; 110 patients/153 samples), VPA (92/166), LTG + VPA (7/12), carbamazepine (CBZ) (8/8), oxcarbazepine (2/3), gabapentin (3/4), levetiracetam (2/3), and topiramate (2/2). A control group treated with OLZ without AEDs was also included (205/247). Dose-adjusted serum concentrations (C:D ratios) of OLZ and its major metabolites (N-desmethyl, N-oxide, and 10-N-glucuronide) were compared between AED subgroups and controls, using linear mixed model analyses with age, gender, and cigarette smoking as covariates. RESULTS: Significantly lower OLZ C:D ratios were found in patients comedicated with VPA (-32%, P < 0.001), VPA + LTG (-31%, P < 0.01), and CBZ (-50%, P < 0.001), compared with controls. The 10-N-glucuronide concentration was significantly lower in patients comedicated with VPA (-26%, P < 0.001), whereas CBZ significantly lowered N-desmethyl (-42%, P = 0.001) and N-oxide (-52%, P < 0.001) metabolite concentrations. C:D ratios of OLZ and metabolites were not significantly affected by comedication with LTG or any of the other AEDs. All covariates were significant determinants of OLZ C:D ratio, that is, age 60 years or above +35% (P < 0.001), female gender +11% (P < 0.01) and smoking -32% (P < 0.001). CONCLUSIONS: Concurrent use of VPA significantly decreases serum concentrations of OLZ to an extent comparable with smoking. The mechanism behind the interaction could not be derived from the results of this study.

Impact of the CYP2D6 genotype on steady-state serum concentrations of aripiprazole and dehydroaripiprazole.

OBJECTIVE: Aripiprazole is an atypical antipsychotic drug which is metabolized by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6). The aim of the present study was to investigate the impact of the CYP2D6 genotype on serum concentrations of aripiprazole (ARI) and to determine the sum of ARI and the active metabolite dehydroaripiprazole (DARI) in psychiatric patients. METHODS: Data on steady-state serum concentrations and the CYP2D6 genotypes of patients treated with ARI were extracted from a routine therapeutic drug monitoring database. The 62 patients included in the analysis were stratified into the following subgroups according to CYP2D6 genotype: *1/*1 (homozygous extensive metabolizers, EMs; n = 37), *1/*3-6 (heterozygous extensive metabolizers, HEMs; n = 17) and *3-6/*3-6 (poor metabolizers, PMs; n = 8). Dose-adjusted serum concentrations (C/D ratios) of ARI and ARI + DARI were compared between the subgroups. RESULTS: The median serum concentration of ARI was 1.7-fold higher in PMs than in EMs (45.5 vs. 26.3 nM/mg, p < 0.01). The observed serum concentration of the active sum of ARI + DARI was 1.5-fold higher in PMs than in EMs (53.9 vs. 37.0 nM/mg, p < 0.05). Numerical differences in serum concentrations between HEMs and EMs were less pronounced, but statistically significant for both ARI (p < 0.05) and ARI + DARI (p < 0.05). CONCLUSION: The present study demonstrates that serum concentrations of both ARI and the active sum of ARI + DARI in psychiatric patients were significantly affected by CYP2D6 genotype. The observed differences in median C/D ratios indicate that PMs typically need 30-40% lower doses to achieve a similar steady-state serum concentration as EMs.

Interactive effects of sex and 5-HTTLPR on mood and impulsivity during tryptophan depletion in healthy people.

BACKGROUND: Serotonin (5-HT) plays a central role in mood regulation and impulsivity. We studied whether healthy men and women react differently on mood and impulsivity measures during acute tryptophan depletion (ATD). We also studied the relative contribution of a functional length triallelic polymorphism in the promoter region of the serotonin transporter, designated 5-HTTLPR, to the behavioral responses to ATD. METHODS: Thirty-nine men and 44 women participated in a randomized, double-blind, parallel group ATD study. Behavioral measures of impulsivity and mood were obtained. RESULTS: During ATD, women reported mood reduction and showed a cautious response style, which is commonly associated with depression. Men showed an impulsive response style and did not report mood reduction. The 5-HTTLPR influenced the mood response to ATD in women. CONCLUSIONS: Healthy men became more impulsive, whereas healthy women showed mood reduction in response to ATD. This suggests that 5-HT could be one mechanism contributing to the sex differences in the prevalence of mood and impulsivity disorders. The influence of 5-HTTLPR on mood responses in women further substantiates the relevance of this variant in the pathophysiology of at least a subgroup of patients with major depressive disorder.

Pharmacokinetic variability of aripiprazole and the active metabolite dehydroaripiprazole in psychiatric patients.

Aripiprazole is a new atypical antipsychotic drug with a partial agonist activity at dopamine 2 and serotonin 1A receptors. The metabolism of aripiprazole involves both cytochrome P450 2D6 (CYP2D6) and CYP3A4. This study investigated the pharmacokinetic variability of aripiprazole and the active metabolite dehydroaripiprazole on the basis of 155 drug monitoring samples from psychiatric patients treated with therapeutic doses of aripiprazole (10-30 mg/day). Serum concentrations of drug and metabolite were determined by liquid chromatographic and tandem mass spectrometric detection. Pharmacokinetic variability was expressed as the range in concentration/dose (C/D) ratios, and the effect of sex and occasionally coprescribed CYP2D6 or CYP3A4 inhibitors/inducers was studied. In addition, the dose-concentration relationship and combined interquartile range of concentrations obtained at low dose (10-15 mg/day) and high dose (20-30 mg/day) were described. Individual C/D ratios ranged 37-fold for aripiprazole, 78-fold for dehydroaripiprazole, and 27-fold for the active sum of aripiprazole + dehydroaripiprazole. Median C/D ratios in male and female patients differed by less than 15%, and none of the differences were significant (P > 0.14). Cases of concurrent CYP3A4 inducers/inhibitors were not found, but three patients were coprescribed the potent CYP2D6 inhibitors paroxetine or fluoxetine. No consistent difference in C/D ratio was observed in these three patients compared with the rest of the patients. There was a proportional dose-concentration relationship in the population, and the combined interquartile ranges were 230 to 960 nmol/L for aripiprazole and 330 to 1210 nmol/L for aripiprazole + dehydroaripiprazole. In conclusion, pharmacokinetic variability of aripiprazole is extensive in psychiatric patients but apparently not dependent on dose or sex. The variability of the pharmacologic active sum of aripiprazole + dehydroaripiprazole is 25% to 30% less than aripiprazole, suggesting that variability of aripiprazole is partly determined by metabolism to dehydroaripiprazole.

Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals.

RATIONALE: Reduced serotonergic activity has been associated with impulsive behavior; however, intervention studies have been scarce. OBJECTIVES: To examine whether induced lowering of serotonin (5-HT) levels would increase behavioral measures of impulsivity. METHODS: Twenty-four healthy young males ingested a mixture of the essential amino acids except for tryptophan in a balanced, randomized, double-blind, placebo-controlled, cross-over study design. The continuous-performance test-identical pairs was administered when the plasma concentration of tryptophan was expected to be at the lowest point. The plasma concentrations of 23 amino acids were measured at baseline and 5 h after the ingestion of the amino acid mixture. RESULTS: The intervention led to a dramatic fall in free and total plasma tryptophan, and the tryptophan/large neutral amino acids ratio. This in turn has been shown to lower the level of 5-HT in the central nervous system. The tryptophan depletion resulted in a statistically significant more impulsive- or disinhibited response style on the continuous-performance test-identical pairs when the subjects were solving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer correct responses and a decreased ability to discriminate between stimuli. CONCLUSIONS: These results indicate that a rapid lowering of tryptophan increases impulsiveness and decreases discriminating ability in normal individuals. The effect of 5-HT depletion on discriminating ability in this study was similar to that previously reported in depressed patients.