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There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an 18F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (Kocc;30–60 value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean Kocc;30–60 was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions.

Tardive dyskinesia (TD) is a movement disorder resulting from treatment with typical and atypical antipsychotics. An estimated 16-50% of patients treated with antipsychotics have TD, but this number may be underestimated. The objectives of this study were to build an algorithm for use in electronic health records (EHRs) for the detection and characterization of TD patients, and to estimate the prevalence of TD in a population of patients exposed to antipsychotic medications. This retrospective observational study included patients identified in the Optum EHR Database who received a new or refill prescription for an antipsychotic medication between January 2011 and December 2015 (follow-up through June 2016). TD mentions were identified in the natural language-processed clinical notes, and an algorithm was built to classify the likelihood that the mention represented documentation of a TD diagnosis as probable, possible, unlikely, or negative. The final TD population comprised a subgroup identified using this algorithm, with ≥1 probable TD mention (highly likely TD). 164,417 patients were identified for the antipsychotic population, with1,314 comprising the final TD population. Conservatively, the estimated average annual prevalence of TD in patients receiving antipsychotics was 0.8% of the antipsychotic user population. The average annual prevalence may be as high as 1.9% per antipsychotic user per year, allowing for a more-inclusive algorithm using both probable and possible TD. Most TD patients were prescribed atypical antipsychotics (1049/1314, 79.8%). Schizophrenia (601/1314, 45.7%), and paranoid and schizophrenia-like disorders (277/1314, 21.1%) were more prevalent in the TD population compared with the entire antipsychotic drug cohort (13,308/164,417; 8.1% and 19,359/164,417; 11.8%, respectively). Despite a lower TD prevalence than previously estimated and the predominant use of atypical antipsychotics, identified TD patients appear to have a substantial comorbidity burden that requires special treatment and management consideration.

ABSTRACTObjectivesThere is a paucity of available research to guide clinical practice in delusional disorder (DD), particularly in late life. This study aimed to evaluate antipsychotic use and treatment outcomes in patients with DD aged 65 years and older. Secondarily, we sought to examine associated clinical features and socio-demographic variables. Design and settingThis descriptive study reviewed all consecutive cases of DD referred to an Australian old age psychiatry service over a 12-year period. Fifty-five patients were assessed in the inpatient and/or community setting, with data verified from a review of all individual medical records. MeasurementsData were collected with respect to antipsychotic use, outcomes, and clinical features. Socio-demographic variables of DD cases were compared to a non-matched comparison group (n=278) and an age and gender matched comparison group with a 1:1 ratio (n=55). ResultsThe predominant type of DD was persecutory (87%). Non-prominent hallucinations were experienced by 18%, and depressive symptoms occurred in 22%. There was a statistically significant association between having DD and social isolation (χ 2= 11.04 (DF=1) p<0.001; McNemar’s test p<0.001). Atypical antipsychotic medication was prescribed in 32 cases, with follow-up permitted in 51 of the 55 cases (mean duration 36.6 months). Sustained recovery occurred in 20%, and improvement in an additional 35% of the study sample. Four patients subsequently developed dementia, and two developed mild cognitive impairment. ConclusionsClinical improvement, including sustained recovery, occurred in more than half of those with late life DD. The majority of those who improved (96%) received atypical antipsychotics.

Second-generation antipsychotics have been thought to cause fewer extrapyramidal side-effects (EPS) than first-generation antipsychotics, but recent pragmatic trials have indicated equivalence. To determine whether second-generation antipsychotics had better outcomes in terms of EPS than first-generation drugs. We conducted an intention-to-treat, secondary analysis of data from an earlier randomised controlled trial (n = 227). A clinically significant difference was defined as double or half the symptoms in groups prescribed first- v. second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). We also examined EPS in terms of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had resolved at these time points. At baseline those randomised to the first-generation antipsychotic group (n = 118) had similar EPS to the second-generation group (n = 109). Indications of resolved Parkinsonism (OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR = 2.2) in the second-generation drug group at 12 weeks were not statistically significant and the effects were not present by 52 weeks. Patients in the second-generation group were dramatically (30-fold) less likely to be prescribed adjunctive anticholinergic medication, despite equivalence in terms of EPS. The expected improvement in EPS profiles for participants randomised to second-generation drugs was not found; the prognosis over 1 year of those in the first-generation arm was no worse in these terms. The place of careful prescription of first-generation drugs in contemporary practice remains to be defined, potentially improving clinical effectiveness and avoiding life-shortening metabolic disturbances in some patients currently treated with the narrow range of second-generation antipsychotics used in routine practice. This has educational implications because a generation of psychiatrists now has little or no experience with first-generation antipsychotic prescription.

Background Paliperidone is a second-generation antipsychotic agent that is effective in the treatment of schizophrenia and schizoaffective disorder as well as an adjunct to mood stabilizers and antidepressants for bipolar and depressive disorders. Paliperidone is available in both oral and injection forms. Here we report an unexpected case of cutaneous allergic reaction induced by paliperidone long-acting injection (LAI) following oral tolerance. Case presentation A 55-year-old man with first episode delusional disorder was treated with paliperidone tablets with tolerance. On day seven he received the paliperidone LAI and developed an allergic reaction in minutes including flushing of the face, widespread urticaria with mild airway constriction. The allergic symptoms were relived following the administration of antihistamine within several minutes. Conclusion The allergic reaction that occurred post administration of the paliperidone LAI but not the oral tablets suggest it is likely due to the excipients in the formulation of the LAI rather than paliperidone itself. This case highlights the necessity of monitoring allergic reactions in psychiatric patients when converting from oral to LAI format of paliperidone.

Antipsychotic drugs fail to achieve adequate response in 30–50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.

Background The aim of the TAILOR trial is to investigate the effect of closely monitored tapering/discontinuation versus maintenance therapy with antipsychotic medication in patients with newly diagnosed schizophrenia or persistent delusional disorder and with minimum 3 months’ remission of psychotic symptoms. Methods and design Two hundred and fifty patients will be included from the psychiatric early intervention program, OPUS, in two regions in Denmark. Inclusion criteria are: ICD-10 diagnoses schizophrenia (F20, except F20.6) or persistent delusional disorder (F22), minimum 3 months’ remission of psychotic symptoms and in treatment with antipsychotic medication (except clozapine). The patients will be randomized to maintenance therapy or tapering/discontinuation with antipsychotic medication in a 1-year intervention. The tapering/discontinuation group will be using a smartphone application to monitor early warning signs of psychotic relapse. Patients will be assessed at baseline, 1-, 2- and 5-year follow-up regarding psychotic and negative symptoms, side-effects of antipsychotic medication, social functioning, cognitive functioning, perceived health status, patient satisfaction, substance and alcohol use, sexual functioning and quality of life. The primary outcome will be remission of psychotic symptoms and no antipsychotic medication after 1 year. Secondary outcome measures will include: co-occurrence of remission of psychotic symptoms and 0–1-mg haloperidol equivalents of antipsychotic medication after 1-year intervention; antipsychotic dose; antipsychotic side effects; negative symptoms; social functioning; cognitive functioning; and patient satisfaction. Exploratory outcomes will include remission, clinical recovery, substance and alcohol use, sexual functioning, quality of life, self-beliefs of coping and user experience of support from health workers. Safety measures will include death, admissions to psychiatric hospital, severe self-harm and psychotic relapses. Discussion The TAILOR trial will contribute knowledge about the effect of tapering/discontinuation of antipsychotic medication in the early phases of schizophrenia and related disorders and the results may guide future clinical treatment regimens of antipsychotic treatment. Trial registration EU Clinical Trials Register – EudraCT number: 2016-000565-23 . Registered on 5 February 2016.

Previous studies of lymphocyte distribution in schizophrenia have yielded inconsistent results, as summarized in the present study. Based on our own original data, potential confounds that might explain these variations are analyzed and discussed. Blood samples from 26 patients with acute paranoid schizophrenia were investigated in comparison with 32 matched healthy controls by flow cytometry (CD3, CD4, CD8, CD19, and CD56 phenotyping). A subgroup of drug-free patients was followed up after 6 weeks of treatment. Cotinine levels and the free cortisol index (FCI) were provided in order to control for medication, smoking, and stress. Cotinine levels correlated with natural killer (NK) cell counts (CD3 − /CD56 + : r  = −0.383, P  = 0.003) while the FCI was related to B cell numbers (CD19 + : r  = 0.390, P  = 0.003). Considering these covariates, a lower level of T helper cells ( P  = 0.010), a reduced CD4/CD8 ratio ( P  = 0.029), and elevated B cells ( P  = 0.008) were found during acute psychosis. After 6 weeks of medication, an inverse pattern was observed in initially drug-free patients: total T cell ( P  = 0.005), T helper ( P  = 0.003), and T suppressor/cytotoxic cells ( P  = 0.005) increased, while B cell counts declined ( P  = 0.049). In conclusion, acute paranoid schizophrenia may be accompanied by a reduced T cell defense and a shift towards B cell immunity, which normalizes in response to treatment. In addition to disease stage or subtype and medication, cigarette smoking and stress are important co-factors.

Background Quality of life (QoL) is considered an important outcome in health research. It can be rated by the patient, or by an external assessor. We wished to identify the predictors of any discrepancies between these two approaches in people with schizophrenia. Methods Patients with DSM schizophrenia and related disorders (N = 80) completed both patient-rated (Lancashire Quality of Life Profile; LQOLP) and assessor-rated (Heinrich’s Quality of Life Scale; QLS) measures of QoL. Results Patient-rated (LQOLP) and assessor-rated (QLS) measures showed a modest correlation ( r  = 0.38). In a regression analysis, independent predictors of subjectively-rated QoL being higher than objectively-assessed QoL in the same patient, were low insight score (BIS), negative symptoms (PANSS), absence of depression (CDSS), and less positive attitude toward prescribed treatment (DAI). Conclusions In people with schizophrenia, scores on objectively- and subjectively-rated measures of quality of life can differ markedly. When comparing subjective to objective assessments, patients with depressive symptoms will value their QoL lower, and those with low insight will value their QoL higher. This has important implications for the utility and interpretation of QoL measures in schizophrenia.