| 1. |
- Andersson, David A., et al.
(författare)
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Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na+/K+ ATPase on EDHF relaxations in the rat hepatic artery
- 2000
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188. ; 129:7, s. 1490-1496
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Tidskriftsartikel (refereegranskat)abstract
- 1. In the rat hepatic artery, the SK(Ca) inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 μM) and d-tubocurarine (100 μM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM). 2. The IK(Ca) inhibitors clotrimazole (3 μM) and 2-chlorophenyl-bisphenyl-methanol (3 μM) strongly depressed EDHF relaxations when each of them was combined with apamin (300 nM). The cytochrome P450 mono-oxygenase inhibitor ketoconazole (10 μM) had no effect in the presence of apamin. 3. Ciclazindol (10 μM), which abolishes EDHF relaxations in the presence of apamin, almost completely prevented the calcium ionophore (A23187) stimulated 86Rb+ influx via the Gardos channel (IK(Ca)) in human erythrocytes. 4. The Na(+/)K+ ATPase inhibitor ouabain (500 μM) and the K(IR) blocker Ba2+ (30 μM) neither alone nor in combination inhibited EDHF relaxations. Ba2+ was also without effect in the presence of either apamin or charybdotoxin. 5. In contrast to EDHF, an increase in extracellular [K+] from 4.6 mM to 9.6, 14.6 and 19.6 mM inconsistently relaxed arteries. In K+-free physiological salt solution, re-admission of K+ always caused complete and sustained relaxations which were abolished by ouabain but unaffected by Ba2+. 6. The present study provides pharmacological evidence for the involvement of SK(Ca) and IK(Ca) in the action of EDHF in the rat hepatic artery. Our results are not consistent with the idea that EDHF is K+ activating Na+/K+ ATPase and K(IR) in this blood vessel.
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| 2. |
- Arnison, Tor, Filosofie doktor, 1984-, et al.
(författare)
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Safety of and response to electroconvulsive therapy during pregnancy : Results from population‐based nationwide registries
- 2023
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Ingår i: Acta Psychiatrica Scandinavica. - : John Wiley & Sons. - 0001-690X .- 1600-0447.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Psychiatric disorders are common during pregnancy, affecting up to 16% of pregnant women. Severe depression and anxiety have significant negative effects on the health of both the mother and the developing fetus. Electroconvulsive therapy (ECT) is considered a treatment option for pregnant women with severe psychiatric disorders when other treatments have been ineffective or pose risks to the fetus. Knowledge of the safety and efficacy of ECT during pregnancy, however, remains limited.Methods: Data were obtained from nationwide registries of pregnant women in Sweden who received ECT for a severe psychiatric disorder from January 2008 to December 2021. ECT-related outcomes in pregnant women were compared by propensity score matching with a group of non-pregnant women who also received ECT. Pregnancy-related outcomes were compared with two additional control groups: one consisting of the same group of women who did not receive ECT during another pregnancy and the other composed of pregnant women admitted to inpatient psychiatric care but who did not receive ECT, matched based on propensity score.Results: Ninety-five pregnant women received ECT during the study period, accounting for 97 pregnancies. The response rate to ECT in pregnant women (n = 54) was similar to the matched control group of non-pregnant women (74% vs. 65%; OR 1.61; 95% CI 0.79-3.27). Rates of adverse events related to ECT were similar to those in the control group. There were no pre-term births or severe adverse outcomes related to the pregnancy, that were close in time to ECT. Therefore, no adverse outcomes related to pregnancy and childbirth could be directly attributed to ECT. The likelihood of premature birth and a 5-min Apgar score <7 in the newborn were both significantly higher in the ECT group, compared with the matched non-ECT group (OR 2.33, 95% CI 1.15-4.73, p = 0.008, and OR 3.68, 95% CI 1.58-8.55, p < 0.001, respectively). By contrast, no significant differences were observed when women in the pregnant ECT group were compared with the same group lacking ECT during another pregnancy.Conclusions: ECT was associated with a positive treatment response in pregnant women with severe psychiatric disorders. The response rate to ECT was similar in pregnant and non-pregnant women. Nevertheless, the risks of premature birth and of a slightly poorer condition in newborns were higher in women who did than did not receive ECT, emphasizing the need for increased attention to severe psychiatric disorders during pregnancy.
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| 3. |
- Bautista, D M, et al.
(författare)
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Pungent products from garlic activate the sensory ion channel TRPA1
- 2005
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:34, s. 12248-12252
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Tidskriftsartikel (refereegranskat)abstract
- Garlic belongs to the Allium family of plants that produce organosulfur compounds, such as allicin and diallyl disulfide (DADS), which account for their pungency and spicy aroma. Many health benefits have been ascribed to Allium extracts, including hypotensive and vasorelaxant activities. However, the molecular mechanisms underlying these effects remain unknown. Intriguingly, allicin and DADS share structural similarities with allyl isothiocyanate, the pungent ingredient in wasabi and other mustard plants that induces pain and inflammation by activating TRPA1, an excitatory ion channel on primary sensory neurons of the pain pathway. Here we show that allicin and DADS excite an allyl isothiocyanate-sensitive subpopulation of sensory neurons and induce vasodilation by activating capsaicin-sensitive perivascular sensory nerve endings. Moreover, allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous systems. These and other results suggest that garlic excites sensory neurons primarily through activation of TRPA1. Thus different plant genera, including Allium and Brassica, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence.
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| 4. |
- Berge, Jonas, et al.
(författare)
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Associations between off-label low-dose olanzapine or quetiapine and cardiometabolic mortality
- 2022
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Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956 .- 1879-1379. ; 149, s. 352-358
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Tidskriftsartikel (refereegranskat)abstract
- Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64–1.15, P = 0.307). However, compared to no treatment, treatment for <6 months was significantly associated with a reduced risk (adjusted HR 0.56, 95% CI 0.37–0.87, P = 0.010) whereas treatment for 6–12 months was significantly associated with an increased risk (adjusted HR 1.89, 95% CI 1.22–2.92, P = 0.004), but not significantly beyond 12 months. Among those treated, each year exposed to an average 5 mg/day was significantly associated with increased cardiometabolic mortality (adjusted HR 1.45, 95% CI 1.06–1.99, P = 0.019). Overall, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. Clinicians should consider potential cardiometabolic sequelae at lower doses.
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| 5. |
- Carli, V, et al.
(författare)
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A Naturalistic, European Multi-Center Clinical Study of Electrodermal Reactivity and Suicide Risk Among Patients With Depression
- 2022
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 765128-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Electrodermal hyporeactivity has been proposed as a marker of suicidal risk. The EUDOR-A study investigated the prevalence of electrodermal hyporeactivity among patients with depression and its association with attempted and completed suicide.Methods:Between August 2014 and March 2016, 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase) were recruited at 15 European psychiatric centers. Each patient was followed-up for 1 year. Electrodermal activity was assessed at baseline with the ElectroDermal Orienting Reactivity Test. Data on the sociodemographic characteristics, clinical diagnoses, and treatment of the subjects were also collected. The severity of the depressive symptoms was assessed through the Montgomery–Asberg Depression Rating Scale. Information regarding number, time, and method of suicide attempts was gathered at baseline and at the end of the 1-year follow-up. The same data were collected in case of completed suicide.Results:Hyporeactive patients were shown to be significantly more at risk of suicide attempt compared to reactive patients, both at baseline and follow-up. A sensitivity of 29.86% and a positive predictive value (PPV) of 46.77% were found for attempted suicide at baseline, while a sensitivity of 35.36% and a PPV of 8.92% were found for attempted suicide at follow-up. The sensitivity and PPV for completed suicide were 25.00 and 0.61%, respectively. However, when controlled for suicide attempt at baseline, the association between hyporeactivity and follow-up suicide attempt was no longer significant. The low number of completed suicides did not allow any analysis.
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| 6. |
- Ekstrand, Joakim, et al.
(författare)
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Ketamine or ECT? What have we learned from the KetECT and ELEKT-D trials?
- 2024
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- Two recent clinical trials, KetECT and ELEKT-D, compared the effectiveness of ketamine and electroconvulsive therapy (ECT) for major depressive disorder. Notably, these trials reported marked differences in ECT's clinical outcomes of, with remission rates of 63% for KetECT and a strikingly lower rate of 22% for ELEKT-D, while the remission rates for ketamine were 46% and 38%, respectively. Considering that the primary objective of both trials was to compare the standard treatment (ECT) with an experimental intervention (ketamine), it is crucial to highlight the pronounced disparities in ECT's clinical outcomes. This article offers a comprehensive comparison of these trials while also exploring how patient characteristics, treatment protocols, and study designs may contribute to such pronounced outcome discrepancies. These differences highlight the heterogeneous nature of depression and underscore the need for personalized treatments. These studies also provide valuable insights into identifying the most suitable candidates for ketamine and ECT.
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| 7. |
- Ekstrand, Joakim, et al.
(författare)
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Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression : A Randomized, Open-Label, Non-Inferiority Trial (KetECT)
- 2022
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 25:5, s. 339-349
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression.METHODS: Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale score ≤10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session.RESULTS: In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52).CONCLUSION: Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.
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| 8. |
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| 9. |
- Gillving, Cecilia, 1999-, et al.
(författare)
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Seizure Duration and Electroconvulsive Therapy in Major Depressive Disorder
- 2024
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome. OBJECTIVE To explore the association between seizure duration, potential confounding variables, and ECT treatment outcome. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study obtained data from the Swedish National Quality Register for ECT. Patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019, were included. The electroencephalographic (EEG) seizure duration from the first ECT treatment session for each patient was used for analysis. Data analyses were performed between March 2021 and May 2024. MAIN OUTCOMES AND MEASURESThe primary outcome was remission, defined as a cutoff score of less than 10 points on the self-assessment version of the Montgomery-& Aring;sberg Depression Rating Scale within 1 week after ECT. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) between different seizure duration groups. Furthermore, the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate were explored. RESULTS Among the 6998 patients included, 4229 (60.4%) were female and the mean (SD) age was 55.2 (18.6) years. Overall, 2749 patients (39.3%) achieved remission after ECT. Patients with EEG seizure duration of 60 to 69 seconds had the highest remission rates compared with patients with seizure duration of less than 20 seconds (OR, 2.17; 95% CI, 1.63-2.88; P < .001). Anticonvulsant medications were associated with shorter seizure duration (eg, lamotrigine: beta coefficient [SE], -6.02 [1.08]; P < .001) and lower remission rates (eg, lamotrigine: adjusted OR, 0.67; 95% CI, 0.53-0.84; P < .001). CONCLUSIONS AND RELEVANCE This study found an association between seizure length and remission from MDD. Use of anticonvulsant medication during ECT was associated with shorter seizure duration and lower remission rates after ECT.
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| 10. |
- Holck, Amanda, et al.
(författare)
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Peripheral serotonin levels as a predictor of antidepressant treatment response : A systematic review
- 2024
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Ingår i: Progress in Neuro-Psychopharmacology and Biological Psychiatry. - 0278-5846. ; 133
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Forskningsöversikt (refereegranskat)abstract
- There are currently no reliable biomarkers to predict clinical response to pharmacological treatments of depressive disorders. Peripheral blood 5-hydroxytryptamine (5-HT; serotonin) has been suggested as a biomarker of antidepressant treatment response, but there has not been an attempt to systematically summarize and evaluate the scientific evidence of this hypothesis. In this systematic review we searched MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials. Twenty-six relevant studies investigating peripheral 5-HT as an antidepressant biomarker were identified. In all, we did not find robust support for an association between baseline 5-HT and treatment response. Several larger studies with lower risk of bias, however, showed that higher baseline 5-HT was associated with a greater antidepressant response to SSRIs, prompting future studies to investigate this hypothesis. Our results also confirm previous reports that SSRI treatment is associated with a decrease in peripheral 5-HT levels; however, we were not able to confirm that larger decreases of 5-HT are associated with better treatment outcome as results were inconclusive.
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