Alice Caldiroli

Misdiagnosis, duration of untreated illness (DUI) and outcome in bipolar patients with psychotic symptoms: A naturalistic study.

BACKGROUND A number of data show the negative role of duration of untreated illness (DUI) on outcome in mood disorders, but no investigation has been carried out about the impact of this variable in bipolar disorder (BD) with psychotic symptoms. Clinical experience shows that many bipolar patients with psychotic symptoms receive other diagnoses and often are chronically treated with first generation antipsychotics, with the effect to reduce duration of untreated psychosis/untreated episode with psychotic symptoms (DUP), but not DUI. Purpose of the study was to define the rate of misdiagnosis and the impact of DUP/DUI on outcome of bipolar patients with psychotic symptoms. METHOD Clinical information (DUP, DUI, first received diagnosis) about bipolar outpatients with psychotic symptoms (N=240) were extrapolated through a retrospective review of the clinical charts, Lombardy database and, if necessary, through clinical interviews with patients and their relatives. Outcome measures included psychiatric and substance abuse comorbidity, occupational status, Global Assessment of Functioning (GAF), number of hospitalizations and of suicidal attempts, number of depressive/manic recurrences. Patients were divided in two groups according to the DUP (1 year) and DUI (8 years) median, and the groups were compared through analyses of variance (ANOVAs) for continuous variables or χ(2) tests for dichotomous ones. Multivariate analysis of variance (MANOVA) with duration of illness as covariate was then performed to eliminate the effect of this variable. Finally, binary logistic regressions were performed considering age at onset, DUI, DUP as independent variables and outcome variables as dependent ones (presence of hospitalizations/suicidal attempts, GAF scores<50, occupational status). RESULTS Most of patients (61.5%) received a first diagnosis different from BD with the most frequent DSM-diagnosis being delusional disorder (17.9%). Patients with longer DUP were not different in outcome measures with respect to patients with shorter DUP. Patients with a DUI >8 years presented higher number of hospitalizations (F=6.04, p=0.015), higher number of manic recurrences (F=5.25, p=0.023), higher number of depressive recurrences (F=7.13, p=0.008) and lower GAF scores (F=17.74, p<0.001). Statistical significance persisted for number of hospitalizations (p<0.001) and GAF scores (p=0.003) after MANOVA. Finally binary logistic regression showed that a longer DUI was predictive of GAF scores<50 (F=17.74, p<0.001). DISCUSSION More than half of bipolar patients with psychotic symptoms receive a different diagnosis at first contact with psychiatric services. DUI (but not DUP) is a predictor of outcome in bipolar patients with psychotic symptoms. This indicates that an early diagnosis and proper treatment with a mood stabilizer (or an atypical antipsychotic with mood stabilizing effects) may improve long-term outcome of these patients. In the light of the naturalistic design of the present paper, these results have to be considered as preliminary and have to be confirmed by prospective controlled studies.

Biological aspects and candidate biomarkers for psychotic bipolar disorder: A systematic review.

We carried out a systematic review of the available literature about potential biomarkers of psychotic bipolar disorder (BD‐P), a specific subset presenting worse outcome and greater risk of relapse than non‐psychotic bipolar disorder (BD‐NP).

The impact of mood episodes and duration of illness on cognition in bipolar disorder

OBJECTIVE A number of studies showed cognitive impairment in bipolar patients but few researches have studied the impact of mood episodes or duration of illness on neuropsychological functioning. METHODS Cognitive functioning was examined in 110 bipolar 1 outpatients with different mood state (mania, major depression, mixed episode and euthymia). The neuropsychological battery included The Visual Search Test, Trail Making Test, Corsi Test, Frontal Assessment Battery (FAB), Cognitive Estimation Task (CET) and Tower of London and it assessed attention, memory and executive/planning functions. Failures in the different cognitive tests were compared between groups using χ(2) tests with Bonferronis corrections. Finally a binary logistic regression was performed in order to find an eventual association between age and duration of illness and CET bizarreness. RESULTS All the symptomatic patients (manic, depressed, mixed) failed more frequently The Visual Search Test in comparison with euthymics (χ(2)=9.882, df=3, p=0.017, phi=0.30; rate of failures: manic patients 32.2%, depressed patients 30.6%, euthymics 0%, mixed patients 18.2%). CET was performed worse by manic and euthymic patients (χ(2)=10.086, df=3, p=0.015, phi=0.31; rate of failures: manic patients 46.4%, depressed patients 22.9%, euthymics 52.1%, mixed patients 18.2%). Finally, a longer duration of illness was found to be predictive of more bizarreness at CET (OR=1.06, p=0.01). CONCLUSIONS Bipolar patients present impairment in different cognitive domains even in euthymic phases. Frontal dysfunction might be associated with a long duration of illness as shown by number of bizarreness at CET in chronic bipolar patients.

Prominent clinical dimension, duration of illness and treatment response in schizophrenia: a naturalistic study.

Objective Preliminary data indicate that predominant positive symptoms are predictive of subsequent treatment response, while negative and cognitive symptoms are associated with poor outcome. Purpose of the present study was to investigate the relation between the predominant clinical dimension, duration of illness and acute antipsychotic response in a sample of schizophrenic inpatients. Methods Fifty-one schizophrenic inpatients, receiving an antipsychotic mono-therapy, were dimensionally assessed at the admission in the Acute Psychiatric Unit of the University of Milan. Treatment response was selected as parameter of outcome and defined as a reduction >50% of baseline total The Positive and Negative Syndrome Scale (PANSS) score. Demographic and clinical variables between responders and non-responders were compared using one-way analysis of variance for continuous variables and χ2 test for dichotomous ones. Binary logistic regression was performed to find if dimensional scores and duration of illness were associated with acute antipsychotic response. Results A longer duration of illness was found in non-responders respect to responders (15.61 years vs. 8.28 years)(F=4.98, p=0.03). Higher scores on PANSS positive sub-scale (OR=1.3, p=0.03), lower scores on cognitive PANSS scores (OR=0.75, p=0.05) and shorter duration of illness (OR=0.93, p=0.04) were found to be predictive of acute antipsychotic response. Conclusion These preliminary results show that a long duration of illness as well as a more severe cognitive impairment is predictive of treatment non-response, indicating a worse outcome for chronic patients with predominant cognitive symptoms.

Augmentative Asenapine in a Recurrent Manic Catatonic Patient with Partial Response to Clozapine

Catatonia is a severe but treatable neuropsychiatric syndrome known since the middle of the nineteenth century. It has been considered for a long time as a subtype of schizophrenia, even though this association occurs only in 10% of cases. In contrast, it is frequently observed in bipolar patients. First-line treatment consists of benzodiazepines, while in case of resistance electroconvulsive therapy (ECT) and clozapine have shown positive results. In addition, recent studies reported the efficacy of some atypical antipsychotics. The present case shows the clinical response to augmentative asenapine in a catatonic manic patient with a partial response to clozapine.

Correlation between neuropsychological and social cognition measures and symptom dimensions in schizophrenic patients

Neurocognitive and social cognition deficits have been largely reported in Schizophrenia (SKZ) but their association with psychopathology remains uncertain. Our purpose was to explore the relationship between symptom dimensions and neuropsychological performances. We enrolled 35 stabilized schizophrenic outpatients of the Department of Psychiatry of Policlinico Hospital, University of Milan, who completed psychiatric Rating Scales, the Brief Assessment of Cognition in Schizophrenia (BACS) and the Executive and Social Cognition Battery (ESCB). Disorganized dimension seems to have the most significant impact on cognition, being associated with performance in several BACS subtests (verbal memory, working memory, motor speed, symbol coding, Tower of London) and ESCB tasks (MET and Hotel task number of tasks attempted, number of broken MET rules, sum of deviations in Hotel Task). Positive dimension correlated with performance in verbal fluency, negative dimension with IOWA Test results, cognitive dimension with MET number of inefficiencies and Eyes test score. Impulsive-aggressive and depressive dimensions weakly correlated only with Faux Pas test. Our study supports the existence of a specific disorganized dimension in SKZ, separated from cognitive dimension evaluated through clinical instruments (e.g. PANSS), but capable of influencing cognitive abilities. Furthermore, it strengthens the validity of ecological tasks in evaluating cognition in SKZ.

Are antidepressants equally effective in the long-term treatment of major depressive disorder?

Few studies have compared simultaneously different antidepressants in long‐term treatment of major depressive disorder (MDD). Long‐term prevention of recurrences should be the main goal of MDD treatment. The purpose of this study was to compare antidepressants of different pharmacological classes in terms of retention in treatment (no discontinuation for recurrences, hospitalizations, side effects).

Psychiatric Conditions in Parkinson Disease A Comparison With Classical Psychiatric Disorders

Psychiatric conditions often complicate the outcome of patients affected by Parkinson disease (PD), but they differ from classical psychiatric disorders in terms of underlying biological mechanisms, clinical presentation, and treatment response. The purpose of the present review is to illustrate the biological and clinical aspects of psychiatric conditions associated with PD, with particular reference to the differences with respect to classical psychiatric disorders. A careful search of articles on main databases was performed in order to obtain a comprehensive review about the main psychiatric conditions associated with PD. A manual selection of the articles was then performed in order to consider only those articles that concerned with the topic of the review. Psychiatric conditions in patients with PD present substantial differences with respect to classical psychiatric disorders. Their clinical presentation does not align with the symptom profiles represented by Diagnostic and Statistical Manual for Mental Disorders and International Classification of Diseases. Furthermore, psychiatry treatment guidelines are of poor help in managing psychiatric symptoms of patients with PD. Specific diagnostic tools and treatment guidelines are needed to allow early diagnosis and adequate treatment of psychiatric conditions in comorbidity with PD.

Pharmacokinetic evaluation of pregabalin for the treatment of generalized anxiety disorder

ABSTRACT Introduction: Pregabalin is an alternative compound to SSRIs and SNRIs for the first-line treatment of generalized anxiety disorder (GAD). Areas covered: We describe the pharmacokinetic properties of pregabalin and their implications for the treatment of GAD. A search in the main database sources (Medline, ISI, Web of Knowledge and Medscape) was performed in order to obtain a comprehensive and balanced evaluation about the clinical implications of the pharmacokinetic properties of pregabalin in the treatment of GAD. The word “pregabalin” was associated with “pharmacokinetics”, “interactions”’, “GAD”, “anxiety” and “tolerability”. No restriction criteria were established in relation to methodology or publication year. Only English-language articles were selected. Expert opinion: Pregabalin is a safe and efficacious compound for GAD treatment. Short half-life (preventing persistence of side effects), absence of active metabolites and no interactions with CYP450 enzymatic system are all favorable pharmacokinetic properties for the treatment of GAD patients, including those with comorbid depressive symptoms or medical conditions. On the other hand, prescription of pregabalin should be handled with caution to minimize the incidence of renal impairment (especially in elderly patients), where a history of substance misuse or concomitant medications (e.g. anti-hypertensives or some antibiotics) are risk factors that can affect renal function.

Obesity and obstetric complications are associated with rapid-cycling in Italian patients with bipolar disorder

BACKGROUND Rapid cycling (RC) worsens the course of bipolar disorder (BD) being associated with poor response to pharmacotherapy. Previous studies identified clinical variables potentially associated with RCBD: however, in many cases, results were discordant or unreplicated. The present study was aimed to compare clinical variables between RC and non RC bipolar patients and to identify related risk factors. METHODS A sample of 238 bipolar patients was enrolled from 3 different community mental health centers. Descriptive analyses were performed on total sample, and patients were compared in terms of socio-demographic and clinical variables according to the presence of RC by multivariate analyses of variance (MANOVAs, continuous variables) or χ2 tests (qualitative variables). Binary logistic regression was performed to calculate odds ratios. RESULTS Twenty-eight patients (11.8%) had RC. The two groups were not different in terms of age, age at onset, gender distribution, type of family history, type of substance use disorder, history of antidepressant therapy, main antidepressant, psychotic symptoms, comorbid anxiety disorders, suicide attempts, thyroid diseases, diabetes, type of BD, duration of untreated illness, illness duration, duration of antidepressant treatment and GAF scores. In contrast, RC patients had more often a history of obstetric complications (p<0.05), obesity (p<0.05) and a trend to hypercholesterolemia (p=0.08). In addition, RC bipolar patients presented more frequently lifetime MDMA misuse (p<0.05) than patients without RC. DISCUSSION Findings from the present study seem to indicate that obesity and obstetric complications are risk factors for the development of RC in BD. In addition, lifetime MDMA misuse may be more frequent in RC bipolar patients.