| 1. |
- Bergendal, A, et al.
(author)
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Concomitant use of two or more antipsychotic drugs is common in Sweden
- 2015
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In: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 5:4, s. 224-31
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Journal article (peer-reviewed)abstract
- To assess the prevalence of concomitant use of two or more antipsychotic drugs and other psychotropic drugs in the Swedish population. Methods: Data for this observational cohort study were collected from the Swedish Prescribed Drug Register including all dispensed drugs to the entire Swedish population (9.4 million inhabitants). We identified all individuals with at least one dispensed prescription of antipsychotic drug during January to June 2008. After 12 months, a second exposure period was chosen. Individuals who were dispensed two or more antipsychotic drugs in both periods were considered long-time users of antipsychotic polypharmacy. Results: In 2008, 1.5% of the Swedish population was dispensed antipsychotic drugs, the majority (75%) using only one antipsychotic drug. Out of individuals who were dispensed 2 or more antipsychotic drugs during the first period, 62% also was also dispensed at least 2 antipsychotic drugs during the second period. A total of 665 different unique combinations were used in 2008. Individuals prescribed two or more antipsychotic drugs during both periods were more often dispensed anxiolytics and sedatives than those who were dispensed only one antipsychotic drug. Elderly were dispensed antipsychotic drugs much more often than younger persons. Conclusions: In Sweden, 25% of patients dispensed antipsychotic drugs receive a combination of two or more antipsychotic drugs. Individuals who are dispensed antipsychotic polypharmacy are more often dispensed anxiolytics and sedatives than those prescribed only one antipsychotic drug. Long-term observational studies are needed to assess the efficacy and safety of such combinations.
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| 2. |
- Borroto-Escuela, DO, et al.
(author)
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Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia
- 2016
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In: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 6:2, s. 77-94
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Journal article (peer-reviewed)abstract
- The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2– N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of pathological allosteric facilitatory 5-HT2A–D2 interaction increasing D2 protomer signaling. Neurotensin (NTS1)–D2 heterocomplexes also exist in the ventral and dorsal striatum, and likely also in midbrain DA nerve cells as NTS1-D2 autoreceptor complexes where neurotensin produces antipsychotic and propsychotic actions, respectively.
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| 3. |
- Brenner, P, et al.
(author)
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Excess deaths in treatment-resistant depression
- 2021
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In: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 11, s. 20451253211006508-
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Journal article (peer-reviewed)abstract
- Patients with treatment-resistant depression (TRD) have an increased mortality risk compared with other patients with depression, but it is not known how this translates into absolute numbers of excess deaths. Methods: Swedish national registers were used to identify a cohort of 118,774 antidepressant initiators 18–69 years old with a depression diagnosis. Patients who initiated a third consecutive treatment trial were classified as having TRD. Flexible parametric survival models were used to estimate the mortality risk due to all causes and external causes (suicides and accidents), comparing TRD patients with patients with other depression while adjusting for clinical and sociodemographic covariates and including interactions with TRD, age, and Charlson comorbidity index (CCI) for a number of somatic comorbidities. Standardized survival was estimated, as were numbers of excess deaths among TRD patients within each age and comorbidity category. Results: Compared with the mortality risk of other depressed patients, patients with TRD experienced excess deaths in most age and comorbidity categories in the range of 7–16 deaths per 1000 patients during 5 years. Highest numbers for all-cause excess deaths were found among patients 18–29 years old with CCI 1, where 16 [95% confidence interval 5–28] of the expected 37 [25–48] deaths per 1000 patients were excess deaths. The majority of the excess deaths were due to external causes. Conclusion: Patients with TRD experience significant numbers of excess deaths compared with other patients with depression.
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| 4. |
- Carlborg, A, et al.
(author)
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Characteristics of bipolar disorder patients treated with immediate- and extended-release quetiapine in a real clinical setting: a longitudinal, cohort study of 1761 patients
- 2015
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In: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 5:1, s. 13-21
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Journal article (peer-reviewed)abstract
- The objective of this work was to study characteristics and clinical treatment patterns of bipolar disorder (BD) patients admitted to hospital and treated with quetiapine (immediate-release [IR] or extended-release [XR] formulations). Methods: BD patients admitted to hospital and prescribed quetiapine IR were followed by linking two Swedish nationwide registries; the hospitalization and drug dispense registries [ClinicalTrials.gov identifier: NCT01455961]. The study period was from 1 January 2008, to end of 31 December 2011. Data was primarily analysed using descriptive methods. Results: Quetiapine IR was used in 1761 patients of whom 1303 subsequently switched to XR (switch XR) and 458 remained on IR (continuous IR). At baseline, Switch XR patients were younger (−3.3 years), more frequently employed (+7.1%), had higher prevalence of single depressive episodes (+6.7%) and anxiety disorders (+5.8%), lower mean daily IR dose (−19.3%) and fewer medications for somatic disorders (−7.5%) than continuous IR patients. During follow up, the number of concomitant psychiatric medications was lower in switch XR patients (−6%) and higher in continuous IR patients (+6%). Mean daily quetiapine dose was 21% higher in switch XR versus continuous IR patients. Prescriptions of lower quetiapine dosages calculated below 50 mg per day in the XR switch and IR continuous groups were seen in 8% versus 10% of the patients, respectively. Conclusions: Differential use of quetiapine XR and IR in bipolar disorder patients with different and important characteristics was demonstrated. Patients who were switched to quetiapine XR had a higher psychiatric disease burden, were younger and had a higher degree of employment. These differences demonstrate the heterogeneity among bipolar disorder patients and indicate the need in clinical practice for individualized treatment to reduce the risk for both patient and society related losses.
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| 5. |
- Eriksson, L, et al.
(author)
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Use of quetiapine XR and quetiapine IR in clinical practice for hospitalized patients with schizophrenia: a retrospective study
- 2012
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In: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 2:6, s. 217-26
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Journal article (peer-reviewed)abstract
- Quetiapine fumarate, a first-line treatment for schizophrenia, exists in two formulations: extended release (XR) and immediate release (IR). This naturalistic, noninterventional study evaluated use of quetiapine XR/IR among in-patients with schizophrenia [ClinicalTrials.gov identifier: NCT01214135]. Data were collected from medical records. Categorical and numerical outcomes were compared using χ2 and t tests. Of 178 enrolled patients, 66% and 34% used quetiapine XR and IR respectively. Based on mean daily dose, XR was used as antipsychotic medication in 64% of patients compared with 40% of patients on IR (dose ≥ 400 mg/day; p = 0.002) and in higher doses than IR (494 versus 345 mg/day; p = 0.001; calculated averages). Schizophrenia was more commonly reported as reason for use of XR than IR (20% versus 0%; p = 0.0003). Patients with comorbid substance abuse or somatic disease were more likely to receive XR ( p = 0.003; p = 0.03). Treatment cessation due to nonadherence was less common in patients on XR (3.4% versus 12%; p = 0.03). Polypharmacy was seen in 98% of patients. Quetiapine XR/IR usage varies in hospitalized patients with schizophrenia. XR is more often used in antipsychotic dosage; IR is more commonly used at lower doses as add-on therapy. Both quetiapine XR and IR have their place in clinical practice and provide treatment choice in schizophrenia.
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| 6. |
- Lieber, Ingrid, et al.
(author)
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Incidence of hyperthyroidism in patients with bipolar or schizoaffective disorder with or without lithium : 21-year follow-up from the LiSIE retrospective cohort study
- 2023
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In: Therapeutic Advances in Psychopharmacology. - : Sage Publications. - 2045-1253 .- 2045-1261. ; 13
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Journal article (peer-reviewed)abstract
- Background: Lithium-associated hyperthyroidism is much rarer than lithium-associated hypothyroidism. Yet, it may be of substantial clinical significance for affected individuals. For instance, lithium-associated hyperthyroidism could destabilise mood, mimic manic episodes and impact physical health. Only few studies have explored incidence rates of lithium-associated hyperthyroidism. Even fewer studies have compared incidence rates according to lithium exposure history.Objectives: To determine the impact of lithium treatment on the incidence rate of hyperthyroidism in patients with bipolar or schizoaffective disorder and assess its aetiology.Design: This study is part of the LiSIE (Lithium - Study into Effects and Side Effects) retrospective cohort study.Methods: Between 1997 and 2017, patients in the Swedish region of Norrbotten with a diagnosis of bipolar or schizoaffective disorder were screened for all episodes of overt hyperthyroidism in form of thyrotoxicosis or thyroiditis. Incidence rates of episodes of hyperthyroidism per 1000 person-years (PY) were compared in relation to lithium exposure; concurrent, previous, or no exposure ever (lithium-naïve patients).Results: In 1562 patients, we identified 16 episodes of hyperthyroidism corresponding to an incidence rate of 0.88 episodes per 1000 PY. Ninety-four percent of episodes had occurred in women. Patients who had concurrently been exposed to lithium, had an incidence rate of 1.35 episodes per 1000 PY. Patients who had previously been exposed to lithium had an incidence rate of 0.79 per 1000 PY. Patients who had never been exposed to lithium had an incidence rate of 0.47 per 1000 PY. There were no significant differences in the risk ratios for patients with concurrent or previous exposure compared with lithium-naïve patients, neither for hyperthyroidism overall, thyrotoxicosis, or thyroiditis.Conclusion: Lithium-associated hyperthyroidism seems uncommon. The risk of hyperthyroidism does not seem significantly higher in patients with current or previous lithium exposure than in lithium-naïve patients.
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| 7. |
- Ott, Michael, et al.
(author)
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Lithium treatment, nephrogenic diabetes insipidus and the risk of hypernatraemia : a retrospective cohort study
- 2019
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In: Therapeutic Advances in Psychopharmacology. - : Sage Publications. - 2045-1253 .- 2045-1261. ; 9
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Journal article (peer-reviewed)abstract
- Background: Hypernatraemia is a serious condition that can potentially become life threatening. It is known that lithium is associated with polyuria and nephrogenic diabetes insipidus, risk factors for hypernatraemia. In this study, we tested the hypothesis that lithium treatment was a risk factor for hypernatraemia.Methods: We performed a retrospective cohort study in the Swedish region of Norrbotten into the effects and potential adverse effects of lithium treatment and other mood stabilizers (LiSIE). For this particular study, we included all patients who had experienced at least one episode with a sodium concentration > 150 mmol/L between 1997 and 2013. Medical records were reviewed regarding past or current lithium exposure, diabetes insipidus and other potential risk factors for hypernatraemia.Results: Of 2463 patients included, 185 (7.5%) had experienced 204 episodes of hypernatraemia within the 17-year review period. In patients 65 years or older, infections dominated as the cause with 51%. In patients younger than 65 years, intoxications, particularly with alcohol, dominated as the cause with 35%. In the whole sample, dehydration accounted for 12% of episodes, 25% of which in the context of suspected or confirmed nephrogenic diabetes insipidus. Of all episodes, 25% resulted in death, with infection being the most common cause of death in 62% of cases.Conclusions: In our sample, infections and harmful use of substances including alcohol were the most common causes of hypernatraemia. Both current and past use of lithium also led to episodes of hypernatraemia, when associated with nephrogenic diabetes insipidus. Clinicians should remain vigilant, have a low threshold for checking sodium concentrations and consider even risk factors for hypernatraemia beyond lithium.
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| 8. |
- Ott, Michael, et al.
(author)
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Management of severe arterial hypertension associated with serotonin syndrome : a case report analysis based on systematic review techniques
- 2019
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In: Therapeutic Advances in Psychopharmacology. - : Sage Publications. - 2045-1253 .- 2045-1261. ; 9, s. 1-32
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Research review (peer-reviewed)abstract
- Serotonin syndrome is thought to arise from serotonin excess. In many cases, symptoms are mild and self-limiting. But serotonin syndrome can become life threatening, when neuromuscular hyperexcitability spins out of control. Uncontainable neuromuscular hyperexcitability may lead to cardiovascular complications, linked to extreme changes in blood pressure. Currently, there is little guidance on how to control blood pressure in hyperserotonergic states. We report a case with treatment-resistant arterial hypertension, followed by a clinical review (using systematic review principles and techniques) of the available evidence from case reports published between 2004 and 2016 to identify measures to control arterial hypertension associated with serotonin syndrome. We conclude that classic antihypertensives may not be effective for the treatment of severe hypertension associated with serotonin syndrome. Benzodiazepines may lower blood pressure. Patients with severe hypertension not responding to benzodiazepines may benefit from cyproheptadine, propofol or both. In severe cases, higher cyproheptadine doses than currently recommended may be necessary.
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| 9. |
- Ott, Michael, et al.
(author)
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Wernicke's encephalopathy - from basic science to clinical practice. Part 1 : understanding the role of thiamine
- 2020
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In: Therapeutic Advances in Psychopharmacology. - : Sage Publications. - 2045-1253 .- 2045-1261. ; 10
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Research review (peer-reviewed)abstract
- Wernicke's encephalopathy (WE) is an acute neuropsychiatric state. Untreated, WE can lead to coma or death, or progress to Korsakoff syndrome (KS) - a dementia characterized by irreversible loss of anterograde memory. Thiamine (vitamin B1) deficiency lies at the heart of this condition. Yet, our understanding of thiamine regarding prophylaxis and treatment of WE remains limited. This may contribute to the current undertreatment of WE in clinical practice. The overall aim of this review is to identify the best strategies for prophylaxis and treatment of WE in regard to (a) dose of thiamine, (b) mode of administration, (c) timing of switch from one mode of administration to another, (d) duration of administration, and (e) use of magnesium along thiamine as an essential cofactor. Evidence from randomized controlled trials and other intervention studies is virtually absent. Therefore, we have to resort to basic science for proof of principle instead. Here, we present the first part of our clinical review, in which we explore the physiology of thiamine and the pathophysiology of thiamine deficiency. We first explore both of these in their historical context. We then review the pharmacodynamics and pharmacokinetics of thiamine, exploring the roles of the six currently known thiamine compounds, their transporters, and target enzymes. We also explore the significance of magnesium as a cofactor in thiamine-facilitated enzymatic reactions and thiamine transport. In the second (forthcoming) part of this review, we will use the findings of the current review to make evidence-based inferences about strategies for prophylaxis and treatment of WE.
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| 10. |
- Reimers, Arne, et al.
(author)
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The emerging role of omega-3 fatty acids as a therapeutic option in neuropsychiatric disorders
- 2019
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In: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 9
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Research review (peer-reviewed)abstract
- The prevalence of neurologic and psychiatric diseases has been increasing for decades and, given the moderate therapeutic efficacy and safety profile of existing pharmacological treatments, there is an urgent need for new therapeutic approaches. Nutrition has recently been recognized as an important factor for the prevention and treatment of neuropsychiatric disorders. The omega-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play critical roles in neuronal cell function and neurotransmission as well as inflammatory and immune reactions that are involved in neuropsychiatric disease states. A large number of experimental and epidemiological studies provide a strong basis for interventional clinical trials that assessed the clinical efficacy of n-3 PUFAs in various neurological and psychiatric disorders. Most of these trials found beneficial effects of dietary supplementation with EPA and DHA, and no serious safety concerns have emerged. This review gives an introduction to recent findings on the clinical efficacy of n-3 PUFAs in various neuropsychiatric disorders and the underlying biochemical mechanisms. In addition, the reader will be enabled to identify common methodological weaknesses of clinical studies on n-3 PUFAs, and suggestions for the design of future studies are given.
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