Jan Brink Valentin

Comparative Effectiveness of Risperidone Long-Acting Injectable vs First-Generation Antipsychotic Long-Acting Injectables in Schizophrenia: Results From a Nationwide, Retrospective Inception Cohort Study

OBJECTIVE To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). METHODS Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinicians/patients choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. RESULTS Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87-1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86-1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86-1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78-1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. CONCLUSIONS In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second-generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects/patient centered outcomes. In future, head-to-head trials and additional nationwide database studies including other SGA-LAIs is needed.

Risk of psychiatric disorders, self-harm behaviour and service use associated with bariatric surgery

To investigate psychiatric outcomes after bariatric surgery, including suicide, self‐harm, psychiatric service use and substance misuse.

Internet-based CBT for social phobia and panic disorder in a specialised anxiety clinic in routine care: results of a pilot randomised controlled trial

Ample studies have demonstrated that internet-based cognitive behavioural therapy (iCBT) for anxiety disorders is effective and acceptable in controlled settings. Studies assessing the clinical effectiveness of iCBT for anxiety disorders among routine care populations are, however, not as numerous. The purpose of this study was to assess the effectiveness of iCBT among anxiety patients, who were on a waiting list for intensive outpatient treatment, in a specialised routine care clinic.1 A randomised controlled pilot trial was conducted. Recruited patients were on a waiting list and had a primary diagnosis of either social phobia or panic disorder. Participants were randomised into either receiving iCBT with minimal therapist contact (received access to the programme FearFighter® (FF) and received support from a clinician via telephone) or no treatment (stayed on the waiting list). The primary outcome was self-reported symptomatic change of anxiety on Beck Anxiety Inventory (BAI). The secondary outcomes were comorbid depression measured on Beck Depression Inventory (BDI-II) and quality of life measured with the EuroQol one-item visual-analogue scale (EQ-vas). All results were analysed by intention-to-treat analyses using a mixed-effects approach. N = 158 patients were assessed for eligibility of which N = 67 met all eligibility inclusion criteria, signed informed consent forms, and were randomised. Post-treatment assessment was completed by N = 47 (70%). In the intervention group, N = 11 (31%) completed all modules of FF. No significant differences of change of symptomatic levels were found between the intervention and control group for anxiety (BAI: mean diff. = 2.42; 95% CI − 1.03 to 5.86; p = 0.17; d = 0.06) or for depression (BDI-II: mean diff. 1.87; 95% CI − 2.25 to 6.00; p = 0.37; d = 0.02). A large and significant effect was found in self-reported quality of life in favour of the experimental group (EQ-vas: mean diff. − 20.88; 95% CI − 30.64 to − 11.11; p < 0.001; d = 0.81). This study was not able to document statistically significant clinical effect of iCBT with minimal therapist contact compared to a waiting list control group in a specialised anxiety clinic in routine care. However, a large and significant effect was seen on self-reported quality of life. Although these results offer an interesting perspective on iCBT in specialised care, they should be interpreted with caution, due to the limitations of the study. A large scale fully powered RCT is recommended.

Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer′s dementia, when controlling for known risk factors, including current antipsychotic exposure, on all‐cause mortality.

Diagnostic conversion to bipolar disorder in unipolar depressed patients participating in trials on antidepressants

OBJECTIVE In unipolar depressed patients participating in trials on antidepressants, we investigated if illness characteristics at baseline could predict conversion to bipolar disorder. METHOD A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years (SD=11.9) participating in three randomized trials on antidepressants conducted in the period 1985-1994. The independent effects of explanatory variables were examined by applying Cox regression analyses. RESULTS The overall risk of conversion was 20.7%, with a mean follow-up time of 15.2 years per patient. The risk of conversion was associated with an increasing number of previous depressive episodes at baseline, [HR 1.18, 95% CI (1.10-1.26)]. No association with gender, age, age at first depressive episode, duration of baseline episode, subtype of depression or any of the investigated HAM-D subscales included was found. LIMITATIONS The patients were followed-up through the Danish Psychiatric Central Research Register, which resulted in inherent limitations such as possible misclassification of outcome. CONCLUSION In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants, the risk of conversion was associated with the number of previous depressive episodes. Therefore, this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely, or at least be informed about the possible increased risk of conversion.

Antipsychotic treatment effects on cardiovascular, cancer, infection, and intentional self-harm as cause of death in patients with Alzheimer's dementia

Abstract Background Alzheimers disease (AD), the most common disease causing dementia, is linked to increased mortality. However, the effect of antipsychotic use on specific causes of mortality has not yet been investigated thoroughly. Methods Utilizing the Danish nationwide registers, we defined a cohort of patients diagnosed with AD. Utilizing separate Cox regressions for specific causes of mortality, we investigated the effects of cumulative antipsychotic dosage after diagnosis and current antipsychotic exposure in the time period 2000–2011. Results In total, 45,894 patients were followed for 3,803,996 person-years. A total of 6129 cardiovascular related deaths, 2088 cancer related deaths, 1620 infection related deaths, and 28 intentional self-harm related deaths are presented. Current antipsychotic exposure increased mortality rate with HR between 1.92 and 2.31 for cardiovascular, cancer, and infection related death. Cumulative antipsychotic dosages were most commonly associated with increased rates of mortality for cardiovascular and infection as cause of death, whereas the associations were less clear with cancer and intentional self-harm as cause of death. Conclusions We showed that cumulative antipsychotic drug dosages increased mortality rates for cardiovascular and infection as cause of death. These findings highlight the need for further investigations of long-term effects of treatment and of possible sub-groups who could benefit from treatment.

Are Weight Status and Cognition Associated? An Examination of Cognitive Development in Children and Adolescents with Anorexia Nervosa 1 Year after First Hospitalisation

Abstract Objective The aim of this study was to characterise the association between the cognitive profile and weight restoration in children and adolescents with anorexia nervosa. Methods The study was a longitudinal, matched case–control, multicentre study. An assessment of cognitive functions was conducted by using the Wechsler Intelligence Scale for Children–III/the Wechsler Adult Intelligence Scale–III, the Test of Memory and Learning–second edition, Trail Making Tests A and B, the Rey–Osterrieth Complex Figure Test and the Cambridge Neuropsychological Test Automated Battery. Results One hundred twenty individuals, 60 patients with anorexia nervosa with mean age of 14.65 (SD 1.820) years and 60 healthy controls with mean age of 14.76 (SD 1.704) years, participated. No association was found between weight recovery and cognitive functions. However, a significant increase in motor speed was found in Trail Making Test A (p = 0.004), Reaction Time (RTI) five‐choice movement time (p = 0.002) and RTI simple movement time (p = 0.011), resulting in a normalisation corresponding to that found in healthy controls. Furthermore, a significantly lower score in the perceptual organization index (p = 0.029) was found at follow‐up. Conclusions Weight recovery appears not to be associated with cognition. Copyright

Are Weight Status and Cognition Associated

Abstract Objective The aim of this study was to characterise the association between the cognitive profile and weight restoration in children and adolescents with anorexia nervosa. Methods The study was a longitudinal, matched case–control, multicentre study. An assessment of cognitive functions was conducted by using the Wechsler Intelligence Scale for Children–III/the Wechsler Adult Intelligence Scale–III, the Test of Memory and Learning–second edition, Trail Making Tests A and B, the Rey–Osterrieth Complex Figure Test and the Cambridge Neuropsychological Test Automated Battery. Results One hundred twenty individuals, 60 patients with anorexia nervosa with mean age of 14.65 (SD 1.820) years and 60 healthy controls with mean age of 14.76 (SD 1.704) years, participated. No association was found between weight recovery and cognitive functions. However, a significant increase in motor speed was found in Trail Making Test A (p = 0.004), Reaction Time (RTI) five‐choice movement time (p = 0.002) and RTI simple movement time (p = 0.011), resulting in a normalisation corresponding to that found in healthy controls. Furthermore, a significantly lower score in the perceptual organization index (p = 0.029) was found at follow‐up. Conclusions Weight recovery appears not to be associated with cognition. Copyright

Effects of Antipsychotics on Secular Mortality Trends in Patients With Alzheimer’s Disease

OBJECTIVE To investigate secular changes in mortality rates between patients with Alzheimers disease (AD) and the general population as well as changes in antipsychotic drug treatment and the association between drug treatment and mortality in patients with AD in Denmark during a 12-year study period. METHODS This nationwide, retrospective cohort study identified all-cause mortality in all Danish patients with incident ICD-10-defined AD from 2000 through 2011. The cumulative antipsychotic dosages from dementia diagnosis until end of study for each participant were calculated and categorized in 1 of 5 groups per the World Health Organization Defined Daily Doses (DDDs). Data were obtained from relevant Danish national registers. RESULTS The study included 32,001 patients (11,194 male and 20,807 female). During the study period, an increasing trend was found in median survival time, but no decline was seen in standardized mortality ratios, which spanned from 1.19 (95% CI, 0.98-1.46) in 2001 to 1.52 (95% CI, 1.38-1.68) in 2011. The findings showed a decline in proportion of patients with incident AD exposed to antipsychotic drugs as well as decline in mean annual cumulative DDDs. Adjusted Cox regression analyses revealed that current exposure to antipsychotic drugs was associated with increased mortality, although hazard ratios declined during the study period from 2.24 (95% CI, 2.07-2.43) in 2000-2002 to 1.24 (95% CI, 1.09-1.41) in 2009-2011, with P values < .001. CONCLUSIONS These findings appear to underscore the current guideline recommendations for using antipsychotic drugs at only the lowest effective dose and only in patients for whom all non-pharmacologic options have been exhausted. Furthermore, these results seem to indicate that the reduced use of antipsychotic drugs has no impact on relative mortality, suggesting that the AD population has gained less from improvements in care of other diseases that impact mortality rates in patients with AD as well as in the general population.

Second-generation LAI are associated to favorable outcome in a cohort of incident patients diagnosed with schizophrenia

OBJECTIVE Investigate the associations of long-acting injectable (LAI) second generation antipsychotic drugs with number of relapses, psychiatric admissions, days hospitalized, intentional self-harm events, and costs linked to hospitalizations in incident patients diagnosed with schizophrenia. METHOD A nationwide, population-based, retrospective study utilizing mirror-image models before and after initiation of LAI SGA. RESULTS 10,509 patients were included as study population, with analyses being conducted on 2223 patients in a six-month period, 1383 in a 12-month period, 713 in a 24-month period. After initiation of LAI antipsychotics, patients experienced a reduction in number of relapses with an incidence rate ratio (IRR) of 0.60 for the first six months, IRR 0.64 for the first 12 months and IRR 0.64 for the first 24 months following initiation of LAI, all P < 0.001. The number of psychiatric admissions was reduced in a similar manner with respective IRR of 0.59, 0.60 and 0.64, all P < 0.001. Psychiatric bed-days were reduced with 58, 100 and 164 days for the respective periods after LAI initiation, all P < 0.001. In a Cox regression model in patients initiated on LAI, higher age at diagnosis, hazard rate ratio (HR) 0.99, 95%CI(0.98-0.99), P < 0.001, and a later calendar year of diagnosis, HR 0.99, 95%CI(0.98-1.00), P < 0.05, were associated with a lower risk of relapse, whereas mainly psychiatric comorbidity, HR 1.07, 95% CI (1.04-1.11), P < 0.001, and cardiovascular disease, HR 1.12, 95%CI(1.01-1.26), P < 0.05, were associated with relapse. CONCLUSION Even though the design does not allow inferences regarding causality, these population-based findings support the use of second generation LAI antipsychotics.