| 1. |
- Akinola, LS, et al.
(författare)
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Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice
- 2022
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 36:11, s. 1280-1293
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Tidskriftsartikel (refereegranskat)abstract
- Because of their implications in several pathological conditions, α4β2* nicotinic acetylcholine receptors (nAChRs) are potential targets for the treatment of nicotine dependence, pain, and many psychiatric and neurodegenerative diseases. However, they exist in various subtypes, and finding selective tools to investigate them has proved challenging. The nicotinic receptor agonist, 5-iodo-A-85380 (5IA), has helped in delineating the function of β2-containing subtypes in vitro; however, much is still unknown about its behavioral effects. Furthermore, its effectiveness on α6-containing subtypes is limited. Aims: To investigate the effects of 5IA on nociception (formalin, hot-plate, and tail-flick tests), locomotion, hypothermia, and conditioned reward after acute and repeated administration, and to examine the potential role of β2 and α6 nAChR subunits in these effects. Lastly, its selectivity for expressed low sensitivity (LS) and high sensitivity (HS) α4β2 receptors is investigated. Results: 5IA dose-dependently induced hypothermia, locomotion suppression, conditioned place preference, and antinociception (only in the formalin test but not in the hot-plate or tail-flick tests). Furthermore, these effects were mediated by β2 but not α6 nicotinic subunits. Finally, we show that 5-iodo-A-85380 potently activates both stoichiometries of α4β2 nAChRs with differential efficacies, being a full agonist on HS α4(2)β2(3) nAChRs, and a partial agonist on LS α4(3)β2(2) nAChRs and α6-containing subtypes as well.
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| 2. |
- Arnone, Danilo, et al.
(författare)
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Efficacy of onabotulinumtoxinA in the treatment of unipolar major depression : Systematic review, meta-analysis and meta-regression analyses of double-blind randomised controlled trials
- 2021
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Ingår i: Journal of Psychopharmacology. - : Sage Publications. - 0269-8811 .- 1461-7285. ; 35:8, s. 910-918
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Forskningsöversikt (refereegranskat)abstract
- Background: OnabotulinumtoxinA is a novel therapeutic intervention whose mechanism of action is believed to modify the negative facial feedback, thus abating symptoms of depression. This putative new antidepressant agent offers minimal systemic side effects and negligible risk of pharmacological interactions. We set out to examine the evidence for the use of onabotulinumtoxinA in major depression.Methods: A systematic search of the literature identified double-blind randomised controlled trials (RCTs) investigating the use of onabotulinumtoxinA in the treatment of major depression versus placebo. Data, reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), was combined in meta-analyses (PROSPERO registration ID: CRD42020183538).Results: The search identified five RCTs (four double-blind) comparing onabotulinumtoxinA to placebo. OnabotulinumtoxinA was more effective than placebo when administered within the 20-40 IU dose range in double-blind RCTs. The analysis was free of publication bias and significantly heterogeneous. Meta-regression analyses indicated that onabotulinumtoxinA was more efficacious in women and in higher doses in female patients and less effective with polypharmacy, especially when an increasing number of antidepressants were prescribed. The effectiveness of onabotulinumtoxinA was higher in more recently published double-blind RCTs.Conclusion: The meta-analysis supports the efficacy of the intervention with the results being highly heterogeneous across studies. In view of the heterogeneity of the findings and the significant moderators of benefit (sex, year of study completion and the interaction between sex and dose), more research is required to better understand the role of onabotulinumtoxinA in the treatment of depression.
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| 3. |
- Falhammar, H, et al.
(författare)
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Reduced risk for hospitalization due to hyponatraemia in lithium treated patients: A Swedish population-based case-control study
- 2021
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 35:2, s. 184-189
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Tidskriftsartikel (refereegranskat)abstract
- Many drugs used in psychiatry have been reported to cause hyponatraemia. However, lithium may be an exception due to its potential for causing nephrogenic diabetes insipidus, but clinical data are largely absent. The objective of this investigation was to study the association between lithium therapy and hospitalization due to hyponatraemia.Methods:This study was a register-based case–control investigation of the general Swedish population. Patients hospitalized with a principal diagnosis of hyponatraemia ( n=11,213) were compared with matched controls ( n=44,801). Analyses using multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations and socioeconomic factors were deployed to calculate the association between severe hyponatraemia and the use of lithium. Additionally, newly initiated (⩽90 days) and ongoing lithium therapy was studied separately.Results:Compared with controls, the unadjusted odds ratio (OR) (95% confidence interval (CI)) for hospitalization due to hyponatraemia was 1.07 (0.70–1.59) for lithium. However, after adjustment for confounding factors the risk was reduced (adjusted OR: 0.53 (0.31–0.87)). Newly initiated lithium therapy was not significantly associated with hyponatraemia (adjusted OR 0.73 (0.35–5.38)). In contrast, for ongoing therapy the corresponding adjusted OR was significantly reduced (adjusted OR: 0.52 (0.30–0.87)).Conclusions:A marked inverse association was found between ongoing lithium therapy and hospitalization due to hyponatraemia.
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| 4. |
- Frick, Andreas, Docent, et al.
(författare)
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Habitual caffeine consumption moderates the antidepressant effect of dorsomedial intermittent theta-burst transcranial magnetic stimulation
- 2021
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Ingår i: Journal of Psychopharmacology. - : Sage Publications. - 0269-8811 .- 1461-7285. ; 35:12, s. 1536-1541
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Tidskriftsartikel (refereegranskat)abstract
- Background:Potentiating current antidepressant treatment is much needed. Based on animal studies, caffeine may augment the effects of currently available antidepressants.Objective:Here, we tested whether habitual caffeine consumption moderates the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) using intermittent theta-burst stimulation (iTBS).Methods:Forty patients with current depressive episodes were randomized to active iTBS (n = 19) or sham treatment (n = 21; shielded side of the coil and weak transcutaneous electrical stimulation) delivered two times per day for 10–15 weekdays. Neuronavigated stimulation was applied to the dorsomedial prefrontal cortex. Symptom improvement was measured using change in self-reported Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pretreatment habitual caffeine consumption was quantified using self-reports of number of cups of coffee and energy drinks consumed the 2 days before the treatment starts.Results:Habitual caffeine consumption was associated with symptom improvement following active iTBS (r = 0.51, 95% confidence interval (CI): 0.08–0.78, p = 0.025) but not following sham treatment (r = −0.02, 95% CI: −0.45 to 0.42, p = 0.938). A multiple regression analysis corroborated the findings by showing a significant caffeine consumption × treatment group interaction (β = 0.62, p = 0.043), but no main effects of treatment group (β = 0.22, p = 0.140) or caffeine consumption (β = −0.01, p = 0.948). No group differences in pretreatment symptom scores or caffeine consumption were detected (p values > 0.86).Conclusion:Habitual caffeine consumption moderated the antidepressant effect of dorsomedial iTBS, consistent with caffeine improving antidepressant pharmacological treatments in animals. Caffeine is an antagonist of adenosine receptors and may enhance antidepressant effects through downstream dopaminergic targets.
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| 5. |
- Golic, Mihaela, et al.
(författare)
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Starting lithium in patients with compromised renal function - is it wise?
- 2021
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 35:2, s. 190-197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known of the risks involved for patients who, at the start of lithium treatment, already have compromised renal function. Aims: To assess the risk of developing severe renal impairment (chronic kidney disease (CKD) 4-5) among those patients and to explore predictors for the progression. Methods: A retrospective longitudinal cohort study using data from Sahlgrenska University Hospital's laboratory database 1981-2017. We compared the risk of developing CKD 4-5 in two patient cohorts: an exposed cohort of 83 patients who had high serum creatinine prior to start of lithium and a reference cohort of 83 patients with normal serum creatinine, matched by gender, duration of lithium treatment and age at the start of lithium treatment. The patients' medical charts were reviewed and the Swedish Renal Registry was used to identify patients with renal replacement therapy. Results: There were no significant differences between the exposed and reference cohorts with respect to our matching criteria. Almost half the patients in the exposed cohort versus only 10% of the reference patients progressed to CKD 4-5 (HR 6.7, 95%CI 3.1-14.3,p< 0.001) during a mean observation time of more than 10 years. The progressors were older at the start of lithium treatment and were characterised by a higher burden of comorbid somatic diseases, in particular cardiovascular diseases. Conclusions: Compromised renal function prior to initiating lithium treatment increases the risk of developing severe renal impairment. Monitoring of renal function should include somatic comorbidity among older patients.
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| 6. |
- Golic, Mihaela, et al.
(författare)
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The low risk for early renal damage during lithium treatment has not changed over time
- 2022
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Modern lithium management guidelines were introduced to improve the renal prognosis of lithium patients. Aims: To examine whether prospects for severe renal impairment (defined as chronic kidney disease at least stage 4 (CKD4)), in long-term lithium patients, have changed over time after the introduction of lithium monitoring guidelines. Methods: The time to and hazard for CKD4 were compared between three patient cohorts who started long-term lithium in three consecutive decades: 1980s, 1990s and 2000s. The follow-up time was 10 years after completion of 1-year treatment. The data were collected from Sahlgrenska University Hospital’s laboratory database. Results: In all, 2169 patients were included: 623 in Cohort 1 (started lithium during 1980s), 874 in Cohort 2 (1990s) and 672 in Cohort 3 (2000s). Compliance with lithium monitoring guidelines improved, and mean serum lithium decreased, through the cohorts. In all, 22 patients developed CKD4 during follow-up. The time to CKD4 was the same in all three cohorts (overall: 10.96 years, 95% confidence interval: 10.94–11 years). Age and serum creatinine concentration at start were significant risk factors, while sex had no prognostic value. After adjusting for the significant covariates, there was no statistically significant difference in the hazard for CKD4 between the three cohorts. Conclusion: The risk for severe renal damage during the first decade of long-term lithium is low, but has not changed over time. Our data suggest that improved compliance with lithium guidelines is not reflected in less risk for severe renal damage. © The Author(s) 2022.
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| 7. |
- Guiraud, J., et al.
(författare)
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Sodium oxybate for the maintenance of abstinence in alcohol-dependent patients: An international, multicenter, randomized, double-blind, placebo-controlled trial
- 2022
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 36:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3-3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6-68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites (n = 3-66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD.
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| 8. |
- Jones, G, et al.
(författare)
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Associations between MDMA/ecstasy use and physical health in a U.S. population-based survey sample
- 2022
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 36:10, s. 1129-1135
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Tidskriftsartikel (refereegranskat)abstract
- 3,4-Methylenedioxymethamphetamine (MDMA/“ecstasy”) is an empathogen that can give rise to increased pleasure and empathy and may effectively treat post-traumatic stress disorder. Although prior research has demonstrated associations between ecstasy use and favorable mental health outcomes, the associations between ecstasy and physical health have largely been unexplored. Thus, the goal of this study was to examine the associations between ecstasy use and physical health in a population-based survey sample. Method: This study utilized data from the National Survey on Drug Use and Health (2005–2018), a yearly survey that collects information on substance use and health outcomes in a nationally representative sample of U.S. adults. We used multinomial, ordered, and logistic regression models to test the associations between lifetime ecstasy use and various markers of physical health (self-reported body mass index, overall health, past year heart condition and/or cancer, past year heart disease, past year hypertension, and past year diabetes), controlling for a range of potential confounders. Results: Lifetime ecstasy use was associated with significantly lower risk of self-reported overweightness and obesity (adjusted relative risk ratio range: 0.55–0.88) and lower odds of self-reported past year heart condition and/or cancer (adjusted odds ratio (aOR): 0.67), hypertension (aOR: 0.85), and diabetes (aOR: 0.58). Ecstasy use was also associated with significantly higher odds of better self-reported overall health (aOR: 1.18). Conclusion: Ecstasy shares protective associations with various physical health markers. Future longitudinal studies and clinical trials are needed to more rigorously test these associations.
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| 9. |
- Ledwos, N, et al.
(författare)
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Therapeutic uses of psychedelics for eating disorders and body dysmorphic disorder
- 2023
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 37:1, s. 3-13
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Tidskriftsartikel (refereegranskat)abstract
- Clinical use of psychedelics has gained considerable attention, with promising benefits across a range of mental disorders. Current pharmacological and psychotherapeutic treatments for body dysmorphic disorder (BDD) and eating disorders (EDs) have limited efficacy. As such, other treatment options such as psychedelic-assisted therapies are being explored in these clinical groups. Aims: This systematic review evaluates evidence related to the therapeutic potential of psychedelics in individuals diagnosed with BDD and EDs. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review of all study designs published to the end of February 2022 that identified changes in ED/BDD symptom severity from psychedelics using validated measures to assess symptom changes. Results: Our search detected a total of 372 studies, of which five met inclusion criteria (two exploratory studies, two case reports, and one prospective study). These were included in the data evaluation. Effects of psychedelics on BDD and various ED symptoms were identified mostly through thematic analyses and self-reports. Conclusions: Our findings highlight that more research is needed to determine the safety and efficacy of psychedelics in BDD and EDs and we suggest avenues for future exploration.
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| 10. |
- Lieber, Ingrid, et al.
(författare)
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Lithium-associated hypothyroidism and potential for reversibility after lithium discontinuation : findings from the LiSIE retrospective cohort study
- 2020
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Ingår i: Journal of Psychopharmacology. - : Sage Publications. - 0269-8811 .- 1461-7285. ; 34:3, s. 293-303
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between lithium and thyroid dysfunction has long been known. However, it remains unknown if lithium-associated hypothyroidism is reversible once lithium treatment has been stopped.Aims: To determine whether lithium-associated hypothyroidism was reversible in patients who subsequently discontinued lithium.Methods: A retrospective cohort study in the Swedish region of Norrbotten into the effects and side- effects of lithium treatment and other drugs for relapse prevention (Lithium – Study into Effects and Side Effects). For this particular study, we reviewed medical records between 1997 and 2015 of patients with lithium-associated hypothyroidism who had discontinued lithium.Results: Of 1340 patients screened, 90 were included. Of these, 27% had overt hypothyroidism at the start of thyroid replacement therapy. The mean delay from starting lithium to starting thyroid replacement therapy was 2.3 years (SD 4.7). In total, 50% of patients received thyroid replacement therapy within 10 months of starting lithium. Of 85 patients available for follow-up, 41% stopped thyroid replacement therapy after lithium discontinuation. Only six patients reinstated thyroid replacement therapy subsequently. Of these, only one had overt hypothyroidism.Conclusions: Lithium-associated hypothyroidism seems reversible in most patients once lithium has been discontinued. In such cases, thyroid replacement therapy discontinuation could be attempted much more often than currently done. Based on the limited evidence of our study, we can expect hypothyroidism to recur early after thyroid replacement therapy discontinuation, if at all.
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