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1.
  • Clapham, Eric (författare)
  • Suicide in schizophrenia and adverse events during antipsychotic medication
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis considers side effects and other adverse events during treatment with antipsychotic medication. All included studies use an epidemiological methodology with data from Swedish population-based health registers. The first two studies utilise a nested case-control design, whereas the third and fourth studies rely on cohort designs.The first study considers the impact of extrapyramidal symptoms on suicidality in a schizophrenia spectrum patient group in Stockholm County in Sweden. In this sample, extrapyramidal symptoms are found to be associated with a decreased risk of suicide.The second study involves suicidal communication, blindly extracted from patient records, as risk factors for suicide among patients with schizophrenia spectrum disorders. More severe forms of suicidal ideation and behaviour, such as suicide attempt, are associated with a higher risk of death by suicide, which is consistent with current clinical practice regarding suicide risk assessments.The third study considers the risk of bone fracture during treatment with antipsychotic medications. The study finds that risperidone is not associated with an increased risk of fracture compared with first-generation antipsychotics.The fourth study considers the risk of perimyocarditis and heart failure during treatment with clozapine and the chemically similar medications olanzapine and quetiapine. It finds that clozapine is associated with a substantially elevated risk of perimyocarditis in the short term and a more modest risk of heart failure in the long term, compared with no antipsychotic treatment. Treatment with at least one of olanzapine or quetiapine is not found to be associated with an increased risk of these adverse cardiac events, compared with no antipsychotic medication.
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2.
  • Gibbs, Anna, et al. (författare)
  • COVID-19-associated mortality in individuals with serious mental disorders in Sweden during the first two years of the pandemic : a population-based register study
  • 2024
  • Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reports at the beginning of the COVID-19 pandemic suggested differences in COVID-19-associated mortality between individuals with serious mental disorders (SMD) and the population at large.Aim: To compare the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden over the two main pandemic years.Methods: We compared the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden during 2020 and 2021. For SMD, we included psychotic disorder, bipolar disorder, and severe depression. The analysis was based on summary data from the Swedish Board of Health and Welfare covering the entire adult Swedish population.Results: The overall relative risk (RR) for experiencing a COVID-19-associated death was 1.66 (CI 1.50–1.83; p < 0.001) for individuals with SMD versus individuals without SMD. The corresponding RRs were 3.25 (CI 2.84–3.71; p < 0.001) for individuals with psychotic disorder, 1.06 (CI 0.88–1.26; p = 0.54) for individuals with bipolar disorder, and 1.03 (CI 0.80–1.32; p = 0.80) for individuals with severe depression. Compared to their respective counterparts in the non-SMD group, in the psychotic disorder and severe depression group, the RR were higher in women than in men. In the bipolar disorder group, the RR was higher in men than in women. The RR of COVID-19-associated death was generally higher in younger individuals with SMD. Individuals with psychosis between 18 and 59 years had the highest RR of COVID-19-associated death with 7.25 (CI 4.54–11.59; p<0.001).Conclusions: Individuals with SMD, and particularly those with psychotic disorders, had a higher risk of COVID-19-associated death than the general population. As this is a pattern also seen with other infections, people with SMD may be similarly vulnerable in future pandemics.
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3.
  • Lieber, Ingrid, 1990- (författare)
  • Affective disorders and their treatments : implications for thyroid function
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundThe relationship between affective disorders, mood-stabilisers and thyroid dysfunction is complex and poorly understood. Symptoms of thyroid dysfunction can overlap with symptoms of affective disorder, destabilise mood, and impact physical health. Subjective symptoms and biochemical abnormalities may not always match, especially when changes in thyroid function are only mild. Therefore, diagnosis and treatment of both hypothyroidism and hyperthyroidism in individuals with affective disorders remain complex. For lithium, a first-line treatment for bipolar disorder, an impact on thyroid function was first described in 1968. Since that time, it has become evident that lithium is much more frequently associated with hypothyroidism than hyperthyroidism. But even for lithium, many aspects of how associated thyroid dysfunction should be handled remain unclear. Aims The overall aim of this thesis was, in five studies, to examine aspects of the diagnosis and treatment of thyroid dysfunction in individuals with affective disorders, with a particular focus on lithium. The individual aims of the five studies were todetermine if lithium-associated hypothyroidism was reversible in individuals who had discontinued lithium.identify patterns and trends in thyroid hormone replacement therapy prescribed for individuals with bipolar or schizoaffective disorder.assess whether elevated thyroxine concentrations (hyperthyroxinaemia) were a risk factor for lithium intoxication caused by a change in tubular renal function.examine the incidence rate and aetiology of lithium-associated hyperthyroidism in individuals with bipolar or schizoaffective disorder.explore the attitudes of practising clinicians towards the diagnosis and treatment of subclinical hypothyroidism in individuals with or without affective disorder or anxiety.MethodsStudies 1–4 were part of the LiSIE (Lithium - Study into Effects and Side Effects) retrospective cohort study. LiSIE compares the effects and adverse effects of lithium treatment and other mood stabilisers in the Norrbotten Region and the Region of Västerbotten over a time period of up to 21 years between 1997–2017. For our studies, we used data from the Norrbotten Region only. Study 5 used a three-round modified Delphi consensus-building process. Study 5 was conducted with clinicians from three specialties, general practice, endocrinology and psychiatry, from two countries with similar health care systems, Sweden and the UK. ResultsStudy 1: Of 1340 potentially eligible individuals with lithium treatment, 90 individuals (who had developed hypothyroidism while treated with lithium and later discontinued lithium), were included. Of these, 27% had overt hypothyroidism at the start of thyroid hormone replacement therapy. Of the 85 individuals available for follow-up, 41% stopped thyroid hormone replacement therapy after lithium discontinuation. Only six individuals reinstated thyroid hormone replacement therapy subsequently. Only one had overt hypothyroidism.Study 2: Of 1564 potentially eligible individuals with bipolar or schizoaffective disorder, 291 (27%) had received thyroid hormone replacement therapy at some point during the 21-year review period. In 41% of cases, thyroid hormone replacement therapy was started for subclinical hypothyroidism. At the start of thyroid hormone replacement therapy, the median thyroid stimulating hormone (TSH) concentration was 6.0 (IQR 4.0) mIU/L. The median free serum thyroxine (fT4) was 11.8 (IQR 3.9) pmol/L. The median TSH concentration at the start of thyroid hormone replacement therapy decreased annually by 0.10 mIU/L, being significantly higher in individuals treated with lithium than in individuals treated with other mood stabilisers.Study 3: Of 1562 potentially eligible individuals with bipolar or schizoaffective disorder, 53 individuals had experienced a total of 65 episodes of unintentional lithium intoxication during the review period. In nine episodes, there was elevated fT4 at the time of lithium intoxication, corresponding to an incidence of 1.3 episodes/1000 person-years. For all nine episodes of unintentional lithium intoxication, we could identify alternative explanations that were more plausible than hyperthyroxinaemia. Study 4: In 1562 individuals with bipolar disorder or schizoaffective disorder, we identified 16 episodes of hyperthyroidism, corresponding to an incidence rate of 0.9 episodes/1000 person-years. Individuals who had concurrently been exposed to lithium, had an incidence rate of 1.3 episodes/1000 person-years. Individuals who had been previously exposed to lithium had an incidence rate of 0.8/1000 person-years. Individuals who had never been exposed to lithium (lithium naïve) had a 0.5/1000 person-years incidence rate. There were no significant differences in the risk ratios for individuals with concurrent or previous exposure compared to lithium-naïve individuals, neither for hyperthyroidism overall, nor for thyrotoxicosis or thyroiditis. Study 5: For the expert panel, 60 clinicians; 20 general practitioners, 20 endocrinologists and 20 psychiatrists were recruited. Fifty-three (88%) participants completed all three rounds. The participants reached a consensus on five of the 26 practice statements. The participants agreed that (a) repeated testing was required for the diagnosis of subclinical hypothyroidism, (b) antibody screening should usually occur, and (c and d) antibody screening would strengthen the indication for thyroid hormone replacement therapy in both individuals with and without affective disorder or anxiety. The participants disagreed with (e) requiring a TSH threshold of ≥ 20 mIU/L before starting thyroid hormone replacement therapy.ConclusionsStudy 1: In most cases, lithium-associated hypothyroidism appears reversible. Therefore, thyroid hormone replacement therapy could be discontinued more often once lithium is stopped. Study 2: In most cases, thyroid hormone replacement therapy was started with mild or absent thyroid function changes. The TSH level at which thyroid hormone replacement therapy was initiated decreased over time. When starting thyroid hormone replacement therapy for subclinical hypothyroidism in people with bipolar or schizoaffective disorder, clinicians must carefully weigh the benefits and risks.Study 3: Lithium intoxication with simultaneously elevated fT4 is uncommon. A direct causal link between elevated fT4 and altered tubular renal function remains elusive. An increased frequency of routine thyroid function tests is unlikely to decrease the risk of lithium intoxication. Study 4: Lithium-associated hyperthyroidism is uncommon. The risk of hyperthyroidism does not differ significantly between lithium-exposed and lithium-naïve individuals.Study 5: Attitudes toward diagnosing and treating subclinical hypothyroidism remain diverse. A threshold of an TSH of at least 20 mIU/L for thyroid hormone replacement therapy start, suggested in a previously published guideline, was deemed too high. As the evidence regarding diagnosis and treatment of subclinical hypothyroidism remains limited, future guidelines should consider the views of a broad range of practising clinicians to increase their clinical acceptability and usefulness. 
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4.
  • Öhlund, Louise, 1983- (författare)
  • Factors affecting the pharmacological treatment of bipolar disorder
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: In patients with bipolar disorder, long-term treatment with mood-stabilisers is often required to prevent manic and depressive episodes. At present, our knowledge remains limited regarding factors that influence the outcomes of mood-stabiliser treatment.Lithium is a first-line treatment of bipolar disorder, thought to be superior regarding the prevention of acute relapse, self-harm and suicide. But despite its therapeutic superiority, patients may find lithium difficult to take long-term. The reasons why patients discontinue lithium treatment remain largely unknown. Neither do we know whether lithium is equally effective in patients with bipolar I and bipolar II disorder. Finally, there is only little evidence on how patients with a dual diagnosis of bipolar disorder and adult attention-deficit hyperactivity disorder (ADHD) should be treated. In this patient group, central stimulant treatment may be of benefit, as long as mood-stabilisers are given simultaneously to prevent manic relapses. However, there are no studies that have explored the impact of central stimulants on suicidal and non-suicidal self-injurious behaviour in patients with such a dual diagnosis.Aim: The overall aim of this thesis was to study three factors that may modify treatment outcomes in patients with bipolar disorder or schizoaffective disorder; (1) adherence to lithium and reasons for lithium discontinuation, (2) impact of lithium discontinuation on clinical course in different bipolar disorder subtypes, and (3) impact of central stimulants on suicidal and non-suicidal self-injurious behaviour in patients with a dual diagnosis of bipolar disorder and ADHD.Method shared by all studies: All three studies were part of LiSIE (Lithium – Study into Effects and Side Effects), a retrospective cohort study in the regions of Norrbotten and Västerbotten, exploring effects and side-effects of lithium and other mood-stabilisers.  For our studies, we identified 1566 individuals who had been diagnosed with bipolar disorder or schizoaffective disorder. Study II and III are based on 1564 patients due to consent withdrawal in one patient and diagnosis reassessment in another. For the respective study included in this thesis, we extracted routine clinical data from the medical records.Study I identified and assessed the reasons for lithium discontinuation in 468 patients with bipolar disorder or schizoaffective disorder in relation to (a) type of underlying disorder, bipolar I or schizoaffective disorder versus bipolar II or other bipolar disorder, (b) gender, and (c) person taking the initiative to discontinue lithium (doctor or patient).Study II applied a mirror-image design to examine the clinical course and need for hospital admissions in 194 patients with either bipolar I or schizoaffective disorder or bipolar II or other bipolar disorder within two years before and after lithium discontinuation.Study III assessed occurrence of suicidal or non-suicidal self-injurious behaviour in 206 patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD. This study also used a mirror-image design, comparing the number of suicide attempts and non-suicidal self-injury events within six months and two years before and after central stimulant initiation.Results: Study I: More than half of all patients discontinued lithium at some point. Lithium discontinuation mainly occurred because of adverse effects. More patients with bipolar II or other bipolar disorder than patients with bipolar I or schizoaffective disorder discontinued lithium because of a perceived lack of effect. Men were more likely to discontinue lithium when feeling well. They were also less likely to consult with a doctor prior discontinuation.Study II: The number of hospital admissions and bed-days doubled after lithium discontinuation. This increase was exclusively attributable to patients with bipolar I or schizoaffective disorder. Not having consulted with a doctor prior to lithium discontinuation or no treatment with an alternative mood-stabiliser at the time of lithium discontinuation led to more admissions.Study III: In patients with a dual diagnosis of bipolar or schizoaffective disorder and ADHD, central stimulant treatment reduced the number of suicide attempts and non-suicidal self-injury events. There was no increase in number of hospital admissions.Conclusion: Lithium discontinuation in patients with bipolar disorder or schizoaffective disorder is common and mainly occurs because of adverse effects. It is important that patients who may benefit from lithium can continue their treatment. Therefore, clinicians should discuss and manage potential adverse effects of lithium treatment with patients before initiation and continuously during treatment. Particularly men may require proactive follow-up since they may be more likely to discontinue their treatment without consulting a doctor.Lithium discontinuation in patients with bipolar I or schizoaffective disorder comes at a cost of deteriorated mental health and increased hospital utilisation. In patients with bipolar II or other bipolar disorder, judged on the impact of discontinuation alone, lithium did not appear to prevent more severe depressive episodes requiring hospital admissions. The higher relapse risk in patients with bipolar I or schizoaffective disorder points towards a need to apply a higher threshold for lithium discontinuation in this group.In patients with both bipolar disorder and ADHD, addition of central stimulant treatment may reduce the risk of suicide attempts and non-suicidal self-injury events. This suggests that central stimulants can be safely given in this patient group, as long mood-stabiliser treatment are given concomitantly.
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