Psychotropic Medication of Acute Episodes of Mood Disorders: Current Prescription Attitude in Two Psychiatric Wards in Cagliari, Italy.

BACKGROUND: Medication of acute episodes of mood disorders has changed over the last decades following the results of randomized clinical trials. OBJECTIVE: The aim of this study was to analyze medication prescribed at discharge from two psychiatric wards. We focused on hospitalization as one of the best opportunities to start prophylaxis. METHODS: We examined retrospectively the clinical records of 357 patients hospitalized for mood episodes in two psychiatric wards in the Cagliari area (SPDC-1 and SPDC-2) between 1 January and 31 December 2016. We focused on the psychotropic medication prescribed at discharge from the hospital. RESULTS: Most patients were discharged with antipsychotics (86%) and/or benzodiazepines (89%). Combined medication was frequent, including various co-administration of first-generation and/or second-generation antipsychotics (26% of patients), or antipsychotics combined with mood-stabilizers (51% of patients). There was a preferential prescription of first-generation antipsychotics in SPDC-1, and of second-generation antipsychotics in SPDC-2. Prescription of lithium was significantly more frequent in SPDC-1. CONCLUSION: Although the treatment was in line with randomized clinical trials, the choice of individual psychotropic agents differed significantly between the two wards. Different prescription attitudes can have consequences on the long-term outcome of patients discharged from the hospital after an acute mood episode.

The role of set-shifting in auditory verbal hallucinations.

BACKGROUND: Auditory verbal hallucinations (AVHs) are a cardinal characteristic of psychosis. Recent research on the neuropsychological mechanism of AVHs has focused on source monitoring failure, but a few studies have suggested the involvement of attention, working memory, processing speed, verbal learning, memory, and executive functions. In this study we examined the neuropsychological profile of patients with AVHs, assuming that the mechanism underlying this symptom could be a dysfunction of specific cognitive domains. METHODS: A large neuropsychological battery including set-shifting, working memory, processing speed, attention, fluency, verbal learning and memory, and executive functions was administered to 90 patients with psychotic disorders and 44 healthy controls. The group of patients was divided into two groups: 46 patients with AVHs in the current episode and 44 who denied auditory hallucinations or other modalities in the current episode. AVHs were assessed with the Psychotic Symptom Rating Scales (PSYRATS); the Launay-Slade Hallucination Scale was used to measure long-term propensity to auditory verbal hallucination-like experiences (HLEs) in the sample. RESULTS: Patients showed poorer performances on all neuropsychological measures compared to the healthy controls' group. In the original dataset without missing data (n=58), patients with AVHs (n=29) presented poorer set shifting and verbal learning, higher levels of visual attention, and marginally significant poorer semantic fluency compared to patients without AVHs (n=29). In the logistic model on the multiple imputed dataset (n=90, 100 imputed datasets), lower capacity of set shifting and semantic fluency distinguished patients with AVHs from those without them. CONCLUSIONS: Patients experiencing persistent AVHs might fail to shift their attention away from the voices; poorer semantic fluency could be a secondary deficit of set-shifting failure.

Deficits in metaphor but not in idiomatic processing are related to verbal hallucinations in patients with psychosis.

There is scant evidence that the verbal cognitive deficits observed in patients with psychosis are related to auditory verbal hallucinations. The understanding of metaphors and idiomatic expressions was investigated in a cohort of 90 patients with active psychosis, and in 44 healthy controls. The Psychotic Symptom Rating Scales (PSYRATS: verbal hallucinations subscale) was used to measure the current verbal hallucinations episode; a subscore of the Launay-Slade Hallucination Scale was used to measure long-term propensity to auditory verbal hallucination-like experiences (HLEs) in the sample. The concurrent influence of education, IQ, and cognitive functioning in memory, attention, fluency, and processing speed on metaphor and idioms processing was investigated. Patients performed worse than healthy controls on all neuropsychological measures. Metaphor, but not idioms processing was poorer in patients with verbal hallucinations (n=46) when compared to patients without verbal hallucinations in the current episode (n=44). By taking into account confounding variables, the ability to produce explanations of metaphors was related to scores on the verbal HLEs in the whole sample of patients. Metaphor-comprehension deficit was related to the occurrence of auditory verbal hallucinations in patients with psychosis, suggesting that abnormal pragmatic inferential abilities have an impact on the mechanisms that cause hallucinatory experiences.

Clozapine toxicity due to a multiple drug interaction: a case report.

INTRODUCTION: We report the case of a multiple drug interaction involving clozapine, antifungals and oral contraceptives, which resulted in an increased clozapine plasma level, pericarditis with pericardial effusion and eosinophilia in a young Caucasian woman. These symptoms and signs disappeared a few days after discontinuation of clozapine. At present, we are not aware of reports of clozapine-antifungals interaction, whereas there is only one other case report on the interaction between oral contraceptives and clozapine. The purpose of this case report is to show the risk of potentially serious adverse effects stemming from drug interactions involving medications routinely used in clinical practice. CASE PRESENTATION: A 29-year-old Caucasian woman diagnosed with a schizoaffective disorder was admitted to a psychiatric unit for acute psychosis (hallucinations, delusions and catatonic behavior). She denied smoking tobacco products and was on long-term oral contraceptives. During the first month of hospitalization she was treated with antipsychotics and for 1 week she took simultaneously fluconazole and miconazole gel, after being diagnosed with oral candidiasis. On the last day of antifungals treatment, 29 days after admission, clozapine was started with resolution of psychotic symptoms. After 3 weeks, her clozapine plasma level had increased to 542 ng/mL and eosinophilia was observed. She complained of nausea, vomiting and palpitations; echocardiography showed echocardiographic abnormalities and pericardial effusion. Oral contraceptives were discontinued and after 1 week clozapine was interrupted, with a complete resolution of side effects and pericardial effusion within 4 days. CONCLUSIONS: Clozapine is metabolized by cytochrome P450. The use of inhibitors or other substrates of cytochrome P450, such as antifungals and oral contraceptives, can cause long-lasting interactions and clozapine toxicity. The Naranjo algorithm shows clozapine is a definite cause of pericarditis (score 9) and both clozapine-antifungals and clozapine-contraceptives interactions resulted probable (score 5) in Drug Interaction Probability Scale. A good knowledge on drugs that act as substrates, inhibitors or inducers of cytochrome P450 is mandatory. When those drugs are used in patients taking clozapine, blood level monitoring of clozapine should be recommended, since a lower dose of clozapine might be required to prevent clozapine toxicity.