- Comparative Study of Postmortem Concentrations of Antidepressants in Several Different Matrices. [Journal Article]
- JAJ Anal Toxicol 2018 May 14
- Peripheral blood (PB) is considered to be the golden standard for measuring postmortem drug concentrations. In several cases, PB is however not available, but information regarding drug findings migh...
Peripheral blood (PB) is considered to be the golden standard for measuring postmortem drug concentrations. In several cases, PB is however not available, but information regarding drug findings might still be crucial in order to determine the cause of death. Antidepressants are frequently detected in postmortem samples from forensic toxicology cases, but the literature investigating concentrations in other matrices than peripheral and heart blood is limited.We here describe a study for comparison of concentrations for a large number of different drugs in six different matrices. A total of 173 postmortem cases were included in the study material. The results from 44 cases with findings of antidepressants (amitriptyline/nortriptyline, citalopram, mianserin, mirtazapine, paroxetine, sertraline, trimipramine and venlafaxine) are presented in this article. Concentrations in peripheral and cardiac blood (CB), pericardial fluid (PF), two muscle samples and vitreous humour (VH) are compared. Ratios between concentrations in different matrices have also been compiled from available literature.All the investigated antidepressants were detected in all different matrices, and comparable concentration levels were found in the different matrices with a few exceptions. Concentrations in VH were generally lower than in the other matrices, and in a few cases with low concentrations in blood the antidepressants were not detected in VH. For most of the cases, ratios of 0.5-2 were found between concentration in PB and that in the other matrices. Some deviant concentrations where however found.This study shows that CB, PF, muscle and VH can provide important indications of the corresponding concentrations in PB when PB is not available.
- Efficacy, acceptability, and tolerability of antidepressant treatments for patients with post-stroke depression: a network meta-analysis. [Journal Article]
- BJBraz J Med Biol Res 2018; 51(7):e7218
- The aim of this study was to investigate the efficacy, acceptability, and tolerability of antidepressants in treating post-stroke depression (PSD) by performing a network meta-analysis of randomized ...
The aim of this study was to investigate the efficacy, acceptability, and tolerability of antidepressants in treating post-stroke depression (PSD) by performing a network meta-analysis of randomized controlled trials of the current literature. Eligible studies were retrieved from online databases, and relevant data were extracted. The primary outcome was efficacy as measured by the mean change in overall depressive symptoms. Secondary outcomes included discontinued treatment for any reason and specifically due to adverse events. Fourteen trials were eligible, which included 949 participants and 9 antidepressant treatments. Few significant differences were found for all outcomes. For the primary outcome, doxepin, paroxetine, and nortriptyline were significantly more effective than a placebo [standardized mean differences: -1.93 (95%CI=-3.56 to -0.29), -1.39 (95%CI=-2.59 to -0.21), and -1.25 (95%CI=-2.46 to -0.04), respectively]. Insufficient evidence exists to select a preferred antidepressant for treating patients with post-stroke depression, and our study provides little evidence that paroxetine may be the potential choice when starting treatment for PSD. Future studies with paroxetine and larger sample sizes, multiple medical centers, and sufficient intervention durations is needed for improving the current evidence.
- Exploding Head Syndrome as Aura of Migraine with Brainstem Aura: A Case Report. [Journal Article]
- JOJ Oral Facial Pain Headache 2018 Spring; 32(2):e34-e36
- This article reports a case of exploding head syndrome (EHS) as an aura of migraine with brainstem aura (MBA). A middle-aged man presented with intermittent episodes of a brief sensation of explosion...
This article reports a case of exploding head syndrome (EHS) as an aura of migraine with brainstem aura (MBA). A middle-aged man presented with intermittent episodes of a brief sensation of explosion in the head, visual flashing, vertigo, hearing loss, tinnitus, confusion, ataxia, dysarthria, and bilateral visual impairment followed by migraine headache. The condition was diagnosed as MBA. Explosive head sensation, sensory phenomena, and headaches improved over time with nortriptyline. This case shows that EHS can present as a primary aura symptom in patients with MBA.
- In vitro assessment of competitive and time-dependent inhibition of the nevirapine metabolism by nortriptyline in rats. [Journal Article]
- BPBiochem Pharmacol 2018 Apr 17; 154:1-9
- Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it i...
Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it is inexpensive, readily absorbed after oral administration and non-teratogenic. In the present work, the mechanism of a previously described pharmacokinetic interaction between NVP and the antidepressant drug nortriptyline (NT) was studied using rat hepatic microsomes. The obtained results showed a competitive inhibition of the NVP metabolism by NT. The three main NVP metabolites (2-OH-NVP, 3-OH-NVP and 12-OH-NVP) where competitively inhibited with similar inhibitory constant values (Ki = 4.01, 3.97 and 4.40 μM, respectively). Time-dependent inhibition of the NVP metabolism was also detected, with a 2.5-fold reduction in the IC50 values of NT for 2-, 3-, and 12-OH-NVP formation when NT was preincubated with the microsomal suspension in the presence of an NADPH-generating system. A concentration-dependent inhibition of the formation of NVP metabolites by the main NT metabolite (10-OH-NT) was also observed, however, the inhibitory potency of 10-OH-NT was much lower than that of the parent drug. The apparent hepatic intrinsic clearance of NVP determined in these in vitro experiments was used to predict the in vivo clearance of NVP using the "well-stirred" and the "parallel-tube" models, resulting in values close to those previously observed in vivo clearance. Finally, a good prediction of the increase in the plasma concentrations of NVP when co-administered with NT was obtained employing the inhibitory constant of NT determined in vitro and the estimated plasma concentration of NT entering the liver.
- Antidepressants for preventing postnatal depression. [Review]
- CDCochrane Database Syst Rev 2018 04 18; 4:CD004363
- CONCLUSIONS: Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.
- Short- and Long-term Effects of Neuromodulators for Unexplained Chronic Cough. [Journal Article]
- OHOtolaryngol Head Neck Surg 2018 Apr 01; :194599818768517
- Objective To evaluate the short- and long-term effects of tricyclic antidepressants (TCAs) and gabapentin in the treatment of unexplained chronic cough (UCC). Study Design Prospective cohort. Setting...
Objective To evaluate the short- and long-term effects of tricyclic antidepressants (TCAs) and gabapentin in the treatment of unexplained chronic cough (UCC). Study Design Prospective cohort. Setting Tertiary care hospital. Subjects and Methods Patients seen between July 2016 and March 2017 were included following a formal workup and clinical evaluation indicative of UCC. Patients were placed on either a TCA (amitriptyline or nortriptyline) or gabapentin. Leicester Cough Questionnaire (LCQ) and percentage improvement scores were obtained prior to treatment initiation and at 2 and 6 months of neuromodulator treatment. A linear mixed model assessed the change in LCQ score between the 2 treatment time points and baseline scores. Results Twenty-eight patients completed a total of 37 neuromodulator trials. Gabapentin demonstrated statistically significant improvement in LCQ scores at 2 months (2.48 points, P≤ .01) and 6 months (5.40 points, P = .01) of treatment as compared with baseline. Patients taking TCAs demonstrated statistically significant improvement of LCQ scores at 2 months of treatment (3.46 points, P≤ .01). However, the majority of patients discontinued treatment, most commonly secondary to the development of tachyphylaxis after 2 months, precluding analysis at 6 months. Conclusion While both neuromodulator classes demonstrated short-term benefit, the majority of patients discontinue treatment prior to 6 months, with patients taking TCAs discontinuing more frequently than patients on gabapentin. Future investigations are warranted evaluating tachyphylaxis and the utility of dual treatment therapies designed to address peripheral and central sensory pathways involved in UCC.
- Estimating environmental fate of tricyclic antidepressants in wastewater treatment plant. [Journal Article]
- STSci Total Environ 2018 Sep 01; 634:52-58
- TCAs are known to be toxicants and endocrine disrupting agents. Generally, after being used, TCAs are passed through wastewater treatment plants (WWTPs) to be treated. However, still trace amounts (n...
TCAs are known to be toxicants and endocrine disrupting agents. Generally, after being used, TCAs are passed through wastewater treatment plants (WWTPs) to be treated. However, still trace amounts (ng/L to μg/L) of TCAs have been founded even in the treated water. Therefore, the aim of this study is to elucidate the environmental behaviors of TCAs in the sewage water from WWTPs (Jeonju, Korea). For the experiments, seven TCAs (amitriptyline, imipramine, clomipramine, desipramine, protriptyline, nortriptyline, and doxepin) were selected. Hydrolysibility, biodegradability, and adsorbability of the selected seven TCAs were evaluated. Based on the results, it was concluded that TCAs are not readily hydrolyzed in water and also not biodegraded by aerobic sludge. The 60% to 85% of TCAs were adsorbed immediately onto the activated sludge within 1 s via electrostatic and hydrophobic interactions. It was clearly observed that adsorption affinities were dependent on the types of activated sludge (i.e. anaerobic and aerobic sludge). The affinities of aerobic and anaerobic sludge towards the TCAs at trace concentrations e.g., 1 to 10 μg/L, were estimated to be in the range from 0.021 ± 0.000 to 0.087 ± 0.000 L/μg and from 0.001 ± 0.000 to 0.108 ± 0.001 L/μg, respectively.
- Antidepressant drug-specific prediction of depression treatment outcomes from genetic and clinical variables. [Journal Article]
- SRSci Rep 2018 Apr 03; 8(1):5530
- Individuals with depression differ substantially in their response to treatment with antidepressants. Specific predictors explain only a small proportion of these differences. To meaningfully predict...
Individuals with depression differ substantially in their response to treatment with antidepressants. Specific predictors explain only a small proportion of these differences. To meaningfully predict who will respond to which antidepressant, it may be necessary to combine multiple biomarkers and clinical variables. Using statistical learning on common genetic variants and clinical information in a training sample of 280 individuals randomly allocated to 12-week treatment with antidepressants escitalopram or nortriptyline, we derived models to predict remission with each antidepressant drug. We tested the reproducibility of each prediction in a validation set of 150 participants not used in model derivation. An elastic net logistic model based on eleven genetic and six clinical variables predicted remission with escitalopram in the validation dataset with area under the curve 0.77 (95%CI; 0.66-0.88; p = 0.004), explaining approximately 30% of variance in who achieves remission. A model derived from 20 genetic variables predicted remission with nortriptyline in the validation dataset with an area under the curve 0.77 (95%CI; 0.65-0.90; p < 0.001), explaining approximately 36% of variance in who achieves remission. The predictive models were antidepressant drug-specific. Validated drug-specific predictions suggest that a relatively small number of genetic and clinical variables can help select treatment between escitalopram and nortriptyline.
- Smoking cessation treatment outcomes among people with and without mental and substance use disorders: An observational real-world study. [Journal Article]
- EPEur Psychiatry 2018 Mar 30; 52:22-28
- CONCLUSIONS: The inclusion of individuals with and without MSUD in the same protocol, allowing for individuals with MSUD undergoing their psychiatric treatment, generates at least comparable success rates between the groups. Predictors of treatment success were similar to those found in the general population. Facilities that treat patients with MSUD should treat tobacco use in order to reduce the disparities in morbidity and mortality experienced by this population.
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- JAMAJAMA 2018 Mar 27; 319(12):1271-1272