[Methylphenidate-induced psychosis in a young adult with newly diagnosed ADHD: A case report].

In view of the ongoing rise of ADHD prescriptions among adults in Iceland, it is important that doctors are aware that psychosis is a rare but at times a serious adverse reaction to such treatment. In 2022 5% of adults were prescribed medication to treat ADHD in Iceland. In this case report we present a case of methylphenidate-induced psychosis in a young man with no previous history of psychotic episodes who required admission to the psychiatric intensive care unit.

[Functional recovery after first episode psychosis rehabilitation in an early intervention psychosis center in Iceland].

BACKGROUND: Because of the early onset and disabling symptoms of schizophrenia spectrum disorders many individuals with these disorders are unemployed from an early age and disability pension rates are high. The aim of this study was to assess functional recovery and identify vocational predictors among young first episode psychosis patients registered in an early intervention psychosis center in Iceland in 2010-2020. METHODS: The study is a retrospective cohort study based on the medical records of those who were discharged from Laugaras, the only early intervention psychosis program in Iceland after six months or longer rehabilitation in 2010-2020 (n=144). Univariate and multivariate logistic regression was used to identify vocational predictors. RESULTS: 75% of patients were unemployed at admission to the early intervention center but over half of the patients were employed or in school at discharge. Vocational rehabilitation was the strongest vocational predictor (OR 13.93, 95% CI 3.85-63.89). Other vocational predictors were those that reflect a disabling psychiatric disorder and social functioning before the onset of early intervention. 66% of patients had a history of cannabis use which had a negative impact on employment and education at discharge. CONCLUSIONS: In spite of intensive rehabilitation at an early intervention center, almost half of the patients were neither employed nor in school at discharge. The strongest vocational predictor was vocational rehabilitation which was also one of few vocational predictors that can be influenced by admission to an early intervention psychosis center. It therefore seems important to ensure that effective vocational rehabilitation is readily available at early intervention psychosis centers.

HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry.

The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E-06) and agranulocytosis (OR = 10.49, P = 1.83E-06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E-08; agranulocytosis: OR = 16.31, P = 1.39E-06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland.

Purpose of the article: Clozapine is the only evidence based treatment for treatment-resistant schizophrenia. Constipation is a well known side effect of clozapine treatment. The aims of this study are to describe the prevalence of constipation and ileus during clozapine treatment of patients with schizophrenia in Iceland and to assess the concomitant use of medication that can cause constipation, and laxatives used to treat constipation. MATERIALS AND METHODS: We identified 188 patients treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital, during the study period 1.1.1998 - 21.11.2014. Cases of constipation and ileus were identified using an electronic search with keywords related to ileus in the patients' electronic health records. Detailed medication use was available for 154 patients that used clozapine for at least one year. RESULTS: Four out of 188 patients were diagnosed with ileus that resulted in admission to hospital. Two of these required a permanent stoma as a consequence of their ileus. Laxatives were prescribed for 24 out of 154 patients (15.4%) while on clozapine. In total 40.9% of the patients either had laxatives prescribed or had constipation documented in the medical records. Apart from clozapine, other medications known to cause constipation were prescribed to 28 out of 154 patients (18.2%). CONCLUSIONS: Constipation is a common problem during clozapine treatment which can progress to full-blown ileus which can be fatal. Clinicians need to monitor signs of constipation during treatment with clozapine and respond to it with lifestyle advice and laxative treatment.

Truncating mutations in RBM12 are associated with psychosis.

Thus far, a handful of highly penetrant mutations conferring risk of psychosis have been discovered. Here we used whole-genome sequencing and long-range phasing to investigate an Icelandic kindred containing ten individuals with psychosis (schizophrenia, schizoaffective disorder or psychotic bipolar disorder). We found that all affected individuals carry RBM12 (RNA-binding-motif protein 12) c.2377G>T (P = 2.2 × 10-4), a nonsense mutation that results in the production of a truncated protein lacking a predicted RNA-recognition motif. We replicated the association in a Finnish family in which a second RBM12 truncating mutation (c.2532delT) segregates with psychosis (P = 0.020). c.2377G>T is not fully penetrant for psychosis; however, we found that carriers unaffected by psychosis resemble patients with schizophrenia in their non-psychotic psychiatric disorder and neuropsychological test profile (P = 0.0043) as well as in their life outcomes (including an increased chance of receiving disability benefits, P = 0.011). As RBM12 has not previously been linked to psychosis, this work provides new insight into psychiatric disease.

Risk of diabetes and dyslipidemia during clozapine and other antipsychotic drug treatment of schizophrenia in Iceland.

BACKGROUND: Type 2 diabetes (T2D) and raised blood lipids are associated with the use of antipsychotics, not least clozapine. AIMS: To describe the prevalence of high blood glucose levels, T2D, and dyslipidemia, in association with the use of clozapine or other antipsychotics in patients with schizophrenia in Iceland. METHOD: This study identified 188 patients treated with clozapine and 395 patients never treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital. The comparison group consisted of Icelandic population controls. Data were obtained on blood glucose, HbA1c, and blood lipid levels from these health records. RESULTS: The prevalence of T2D was 14.3% in the clozapine group, where the mean age was 51.2 years, and 13.7% in the never-on-clozapine group, where the mean age was 58.6 years. Males on clozapine were 2.3-times more likely and females 4.4-times more likely to have developed T2D than controls from an age-adjusted Icelandic cohort, while males on other antipsychotics were 1.5-times more likely and females 2.3-times as likely to have T2D than controls. Only one case of ketoacidosis was identified. Triglyceride levels were significantly higher in both treatment groups compared to controls in the age-adjusted Icelandic cohort. CONCLUSIONS: Clinicians must take active steps to reduce the risk of T2D and raised triglycerides in patients with schizophrenia. Antipsychotics were associated with a greater risk of T2D developing in females compared to males.

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

BACKGROUND: Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. METHODS: The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. RESULTS: The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm3). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. CONCLUSIONS: Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.

Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records.

BACKGROUND: Clozapine is the only drug approved for treatment-resistant schizophrenia. There is evidence that clozapine is underutilized. AIMS: To evaluate the initiation and discontinuation of clozapine at Landspitali University Hospital in Iceland and the prevalence of antipsychotic polypharmacy in clozapine-treated patients. METHODS: The study is a part of an ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients on clozapine or who have been on clozapine by using a keyword search in the electronic health records and by reviewing their medical records. RESULTS: Mean age at first treatment with clozapine was 37.8 years. Mean follow-up period on clozapine was 11 years. After 20 years of treatment 71.2% of patients were still on clozapine. After one year of treatment 84.4% of patients were still receiving clozapine treatment. We estimate that 11.4% of patients with schizophrenia in Iceland are taking clozapine and that 16% have been treated with clozapine at some point. Polypharmacy is common, since nearly 2/3, 65.6%, of patients taking clozapine use at least one other antipsychotic and 16.9% are also receiving depot injections. CONCLUSIONS: We need to increase the awareness of psychiatrists in Iceland with regard to treatment with clozapine, since only about half of the estimated population of patients with treatment-resistant schizophrenia in Iceland have ever been treated with clozapine. Nearly two thirds of patients who are prescribed clozapine in Iceland remain on it long-term.

[The Preadmission Nursing Home Assessment (PNHA) in Iceland in 1992-2001 - Relationship to survival and admission to a long term care facility.].

OBJECTIVE: PNHA is a standardized evaluation of the elderly which everyone who applies for an admission to long term care (LTC) in Iceland must undergo. The objective of this study is to describe the elderly who asked for an admission to LTC in The Reykjavík metropolitan area and in Akureyri over a 10 year period. A special attention is paid to factors that could possibly predict survival after PNHA. MATERIAL AND METHODS: Every PNHA evaluation is stored in a database by SKYRR Inc. Information from that database regarding all who lived in the greater Reykjavík area and Akureyri and had undergone their first PNHA during the period from January 1st 1992 to 31st of December 2001, was collected. Information about survival was collected from the the Icelandic national registry. There were 4272 individuals in the study group. SPSS was used for statistical analysis. RESULTS: The average enrolment age of men in nursing homes(NH) in Reykjavík was 82.7 -/+ 0.5 years and for women 84.4 -/+ 0.4 (p<0.01). Men were about one third of residents in NH's. The average waiting time for men from the first PNHA to NH placement was 219 -/+ 20 days and for women 290 -/+ 22 days (p<0.01). Of those who were waiting for NH's, 22% of men and 14% of women died without being admitted (p<0,01). The mean survival of men in NH's in Reykjavík was 2.5 -/+ 0.2 years and for women 3.1 -/+ 0.2 years (p<0.01). Factors predicting longer survival for men in Reykjavík were lower age, good mobility and being able to eat but for women the factors were lower age and good mobility. CONCLUSIONS: It's in all stakeholders' interest that elderly people are enabled to live at home for as long as possible. Factors that predict survival should be taken into account when the elderly are prioritized for admission to NH's so that elderly who are predicted to have the lowest survival rate of assessed are those admitted first.