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Ilaria Cuomo,1,2 Georgios D Kotzalidis,1 Simone de Persis,2 Daria Piacentino,1 Filippo Perrini,2 Emanuela Amici,2 Sergio De Filippis1,2 1Department of Neurosciences, Mental Health, and Sensory Organs (NESMOS), Sapienza School of Medicine and Psychology, Sant’Andrea Hospital, Rome, Italy; 2Department of Neuropsychiatry, Villa von Siebenthal Neuropsychiatric Hospital and Clinic, Genzano di Roma, Rome, Italy Background: To overcome nonadherence in patients with psychosis switch to long-acting injectable (LAI) antipsychotic formulations is adopted. Most oral versus LAI comparisons showed similar antipsychotic responses. Psychoses often overlap with substance use disorder (SUD). Head-to-head LAI comparisons have hitherto focused only on non-comorbid populations. Objective: The objective of this study was to compare two LAIs, administered for 12 months, in initially hospitalized patients with psychosis comorbid with SUD in their clinical and quality of life (QoL) outcomes. Patients and methods: Inpatients were recruited during 2016 and switched randomly to 400 mg intramuscular aripiprazole monohydrate (AM) (N=50) or to 100 mg intramuscular paliperidone palmitate (PP) once-monthly (N=51); patients were discharged and followed up for 12 months. Patients were rated at baseline and after 1 year through the Clinical Global Impression scale – severity (CGIs), substance craving intensity was rated through a visual analog scale for substance craving, and QoL through the World Health Organization (WHOQOL-BREF) scale. We addressed confounders with backward stepwise logistic regression and three-way analysis of variance. Results: PP were older and had more cases of schizophrenia spectrum and less bipolar disorders than AM, but AM had a stronger craving for substances at baseline. Both LAIs were associated with significant improvements in all outcomes, with AM displaying stronger effect sizes than PP. The two groups did not differ on baseline WHOQOL-BREF scores in any domain, but at the 1-year follow-up, AM fared better on all domains. The two groups did not differ in final severity, but PP scored higher than AM in craving at the 1-year endpoint. Limitation: The CGIs is not a refined tool for severity and the substance craving may be subject to recall bias. Conclusion: 1-year AM and PP was followed by improved clinical status and QoL and reduced substance craving in a population with psychosis and SUD comorbidity. AM, compared to PP, improved craving and QoL at the 1-year follow-up. Keywords: psychosis, schizophrenia spectrum and other psychotic disorders, bipolar disorder, long-acting injectable antipsychotic drugs, aripiprazole once-monthly, paliperidone once-monthly

Background/Objectives : Lithium taken during pregnancy was linked in the past with increased risk for foetal/newborn malformations, but clinicians believe that it is worse for newborn children not to treat the mothers' underlying psychiatric illness. We set to review the available evidence of adverse foetal outcomes in women who received lithium treatment for some time during their pregnancy. Methods : We searched four databases and a register to seek papers reporting neonatal outcomes of women who took lithium during their pregnancy by using the appropriate terms. We adopted the PRISMA statement and used Delphi rounds among all the authors to assess eligibility and the Cochrane Risk-of-Bias tool to evaluate the RoB of the included studies. Results : We found 28 eligible studies, 10 of which met the criteria for inclusion in the meta-analysis. The studies regarded 1402 newborn babies and 2595 women exposed to lithium. Overall, the systematic review found slightly increased adverse pregnancy outcomes for women taking lithium for both the first trimester only and any time during pregnancy, while the meta-analysis found increased odds for cardiac or other malformations, preterm birth, and a large size for gestational age with lithium at any time during pregnancy. Conclusions : Women with BD planning a pregnancy should consider discontinuing lithium when euthymic; lithium use during the first trimester and at any time during pregnancy increases the odds for some adverse pregnancy outcomes. Once the pregnancy has started, there is no reason for discontinuing lithium; close foetal monitoring and regular blood lithium levels may obviate some disadvantages of lithium administration during pregnancy.

Background: Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS., Methods: We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity., Results: TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus)., Conclusions: We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Age-at-onset (AAO) affects psychiatric disorder outcome; substance (SUDs) or alcohol use disorders (AUDs) may influence their onset. Affective temperaments may affect early AAO and drug-use proneness. Objectives: To investigate whether SUD/AUD moderated temperamental effects in determining AAO of mental disorders. Methods: We included 300 post-acute inpatients with schizophrenia-spectrum and other psychotic (SSOPDs), major depressive (MDD) or bipolar (BD) disorders (168 men; mean age, 40.63 years ± 11.82 men, 43.21 years ± 12.69 women) with (N = 110) or without (N = 190) SUD/AUD. Patients completed cross-sectionally TEMPS-A. We carried moderation analysis with each regression-significant TEMPS temperament as independent variable, SUD/AUD presence/absence as dichotomous moderator, and AAO as dependent variable. Significance was set at p  < 0.05. Results: AAO was lower in patients with SUD/AUD diagnosis than in patients without (23.74 ± 10.09 vs . 27.73 ± 10.35, respectively, p  = 0.001, η2 = 0.034). SUD/AUD patients scored higher on the hyperthymic (10.22 ± 4.08, p  < 0.001, η2 = 0.069) and irritable (8.26 ± 4.69, p  < 0.01, η2 = 0.026) temperaments than nonSUD/AUD patients. Moderation analysis showed only direct effects of irritable (β = -0.55, p  < 0.005) and hyperthymic (β = -0.95, p  < 0.001) temperaments on AAO and no significant SUD/AUD and interaction effects. Limitations . Cross-sectional design. Conclusions: When irritable and hyperthymic traits prevail over other temperaments, AAO is earlier in SSOPDs, MDD, and BD. SUD/AUD presence/absence does not moderate the relationship between temperament and AAO.

Background: Long-acting injectable (LAI) aripiprazole was found to be efficacious in schizophrenia. In common clinical practice, the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence. Recently, some investigators advanced the idea of early LAI use also in young people with schizophrenia at their first psychotic episode (FEP). Objective: Our study aimed to assess the effect of LAI aripiprazole once monthly (AOM) in the treatment of FEP in patients aged 18-26 years. Methods: We included 50 patients with DSM-5 schizophrenia as assessed with SCID, and used the Clinical Global Impressions Scale-Severity of Illness (CGI-S) and the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity and the World Health Organization Quality of Life (WHOQOL), the Short Form Health Survey (SF-36) and the Personal and Social Performance Scale (PSP) to assess quality of life (QoL) and global health perception at baseline and 3, 6, 9, and 12 months after the first AOM injection. Results: AOM was associated with a progressive improvement, compared to baseline, of both positive ( p < 0.001) and negative ( p < 0.001) symptoms and in general psychopathology ( p < 0.001) and decrease in global severity ( p < 0.001). We also observed progressive improvement in QoL and social and personal functioning. Treatment adherence was 78% at study endpoint. Our results support that AOM may improve psychotic symptoms, QoL and social functioning in young FEP patients. Further studies should compare AOM to its oral formulation in the treatment of young patients with schizophrenia at the outset of their illness., (Copyright © 2020 Giordano, Tomassini, Cuomo, Amici, Perrini, Callovini, Carannante, Kotzalidis and De Filippis.)

Background: Several second-generation antipsychotics (SGAs) are available in long-acting injectable (LAI) formulations., Objective: To systematically review the effects of the two formulations, Monohydrate and Lauroxil, of Aripiprazole LAI in patients with schizophrenia and bipolar disorder during an acute episode or during maintenance treatment., Methods: On September 18, 2018, we adopted the following search strategy: (aripiprazole OR OPC-14597 OR Abilify) AND (long-acting OR depot OR LAI OR once monthly OR prolonged release OR monohydrate OR lauroxil) on PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials. Furthermore, we searched the ClinicalTrials.gov site for possible additional studies., Results: We included 28 papers dealing with randomised assignment of aripiprazole LAI formulations in schizophrenia and bipolar disorder in survival studies after stabilisation, in acute studies, and in head-to-head comparisons. Both monohydrate and lauroxil formulations reduced relapses/recurrences with respect to comparators (placebo or 50 mg once-monthly monohydrate) and improved symptomatology in acute schizophrenia., Limitations: Only a small number of studies were included in our review, with widely overlapping samples. While a high proportion of studies were wholly or partly industry-sponsored, their outcomes do not appear to have been affected., Conclusion: Aripiprazole LAI may to be efficacious in reducing relapse of schizophrenia and bipolar disorder in the long term in stabilised patients and in improving symptoms of schizophrenia during its acute phase, with both monohydrate and lauroxil formulations showing efficacy.

Background: Placebo response appears to be increasing in antidepressant, antipsychotic and various internal medicine trials. A similar trend has been reported for OCD during 1989-1999. Placebo response is generally considered as the extent to which placebo treatment is associated with core symptom improvement. In this analysis, we used Joinpoint regression to assess the time trend of both placebo response and placebo responder rates according to the year of publication with no time restriction in OCD drug trials., Methods: We included drug and/or psychotherapy trials vs. placebo from PubMed, Embase, CINAHL, and PsycINFO retrieved through the search (placebo OR sham) AND (obsessive* OR OCD). We included studies through investigator consensus. We then performed on data of included studies log-linear joinpoint segmented regression models using a p<0.05 cutoff., Results: We included 113 studies from 112 published papers. Placebo mean annual response rates in OCD studies significantly increased from 1991 to 2017 with an annual percent change (APC) of 0.66%, while placebo mean annual responder rates also significantly increased from 2010 to 2017, with an APC of 5.45%. Drug mean annual response rates in OCD studies significantly increased from 1987 to 2012 with an APC of 0.72%, while the corresponding responder rates did not show statistically significant APC changes between 1984 and 2017., Conclusion: We observed a tendency for placebo to increase both measures of response in OCD clinical drug trials through the years that tend to approximate the responses shown by drugs. Changes in the type of study (moving from classical head to head comparisons to add-on studies in treatmentresistant populations) and countries involved in experimentation may partially account for some portion of these results. It appears that placebo effects are becoming more elusive and out of control., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Bipolar disorder (BD) is often treated with anticonvulsants. Lacosamide has not been tested in BD. We assessed its effects in a hospital setting in patients with BD without epilepsy., Methods: We treated 102 consecutive hospitalized patients with acute BD with lacosamide 50-300 mg/day. We compared this sample with a retrospective sample treated with other antiepileptics (OAE). We rated patients after 3, 7, 15, and 30 days of treatment with the Brief Psychiatric Rating Scale, Young Mania Rating Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Clinical Global Impressions - Severity, and Global Assessment of Functioning., Results: Patients receiving lacosamide were significantly younger and had fewer mixed episodes at intake, and less substance use disorder comorbidity than those receiving OAE. Both groups showed positive effects on all measures. The two groups did not differ on any clinical measure at baseline, but from the 3rd day on, lacosamide patients fared better than OAE patients on the Young Mania Rating Scale and Clinical Global Impressions - Severity and worse on the Hamilton Anxiety Rating Scale. From the 15th day, OAE patients scored better on the Brief Psychiatric Rating Scale. Global Assessment of Functioning scores were significantly more improved in the lacosamide patients. Age, substance use disorder comorbidity, episode type, and educational level significantly affected results. No interactions were found amongst these parameters., Conclusion: Lacosamide was effective in reducing psychopathology, mania, depression, and anxiety and in improving global functioning in patients with BD-I/II disorder in the short term, with few side-effects. Lacosamide improved mania, clinical severity, and global functioning better than OAE at doses lower than those used in epilepsy., (© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.)

Background and Aim of the Work: Mood disorders are often complicated by comorbidity with epilepsy. Anxiety and personality disorders may worsen prognosis and treatment outcome. Lacosamide has been recently introduced as adjunctive treatment for partial epilepsy. Its mechanism consists of selective slow inactivation of voltage-gated sodium channels, thus promoting an extended stabilisation of cell membranes. Antiepileptic drugs have been largely used since the 1950s in psychiatry as mood stabilisers due to their membrane stabilising and anti-kindling effects. Like lithium, antiepileptic drugs are first choice treatment for Bipolar and Cyclothymic Disorders., Methods: We tested the efficacy of the most recent antiepileptic medication, lacosamide, in a patient with simultaneously occurring cyclothymic disorder, severe post-traumatic stress disorder, and fronto-temporal epilepsy. Lacosamide was titrated up to 200 mg/day, added on ongoing 750 mg/day lithium, 15 mg/day oral aripiprazole then switched to 400 mg/month long-acting aripiprazole, and 2 mg/day N-desmethyldiazepam., Results: We observed EEG normalisation one month later, along with reduced anxiety and an additive effect to lithium-induced stabilisation of mood fluctuations since the second week of lacosamide addition., Conclusions: Further studies with this drug in the bipolar spectrum are warranted.

Background: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other collaborators. This hypothesis supports that in bipolar disorder, mania leads to depression, while depression does not lead to mania., Objective: To identify evidence in literature that supports or falsifies this hypothesis., Method: We searched the medical literature (PubMed, Embase, PsycINFO, and the Cochrane Library) for peer-reviewed papers on the primacy of mania, the default mode function of the brain in normal people and in bipolar disorder patients, and on illusion superiority until 6 June, 2016. Papers resulting from searches were considered for appropriateness to our objective. We adopted the PRISMA method for our review. The search for consistency with PoM was filtered through the neurobiological results of superiority illusion studies., Results: Out of a grand total of 139 records, 59 were included in our analysis. Of these, 36 were of uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was contrary, but the latter pooled patients in their manic and depressive phases, so to invalidate possible conclusions about its consistency with regard to PoM. All considered studies were not focused on PoM or superiority illusion, hence most of their results were, as expected, unrelated to the circuitry involved in superiority illusion. A considerable amount of evidence is consistent with the hypothesis, although indirectly so., Limitations: Only few studies compared manic with depressive phases, with the majority including patients in euthymia., Conclusion: It is possible that humans have a natural tendency for elation/optimism and positive self-consideration, that are more akin to mania; the depressive state could be a consequence of frustrated or unsustainable mania. This would be consistent with PoM.

Background: Asenapine is a second-generation antipsychotic approved in Europe for treating moderate-to-severe manic episodes in adults affected by type I bipolar disorder (BD-I). We aimed to compare its efficacy in psychiatric inpatients with BD-I, with or without substance use disorder (SUD)., Methods: We administered flexible asenapine doses ranging from 5-20 mg/day to 119 voluntarily hospitalized patients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) BD-I diagnosis, with or without SUD. Patients were assessed with clinician-rated questionnaires [i.e. Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Global Assessment of Functioning (GAF)]. Assessments were carried out at baseline (T0, prior to treatment), and 3 (T1), 7 (T2), 15 (T3), and 30 days (T4) after starting treatment for all clinical scales and at T0 and T4 for the GAF., Results: Patients improved on all scales ( p < 0.001) across all timepoints, as shown both by paired-sample comparisons and by applying a repeated-measures, generalized linear model (GLM). Patients without comorbid SUD showed greater reductions in BPRS scores at T2 and T3, greater reduction in YMRS scores at T3, and lower HARS scores at all timepoints. HDRS scores did not differ between the two groups at any timepoint. However, the reduction in HARS scores in the comorbid group was stronger than in the BD-I only group, albeit not significantly. Side effects were few and mild-to-moderate., Conclusions: The open-label design and the relatively short observation period may expose to both type I and type II statistical errors (false positive and false negatives). Asenapine showed effectiveness and safety in hospitalized BD-I patients. Its effect was stronger in patients without comorbid SUD., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to identify hiccup cases among patients hospitalized in a psychiatric ward and focus on their treatment, so to establish intervention risk., Methods: We reviewed records of 354 consecutively admitted patients during the year 2013 to identify hiccup cases., Results: Hiccup occurred in 7 patients on both aripiprazole and benzodiazepines and in one on delorazepam. No patient on aripiprazole alone developed hiccup. No patient on drugs other than aripiprazole or benzodiazepines developed hiccup. The symptom subsided in 3 cases upon discontinuing aripiprazole and in 5 cases after discontinuing the benzodiazepine (including the case on delorazepam alone); in 2 cases of persistent hiccup, the symptom resolved after adding the calcium channel blocker, pregabalin. All patients developing hiccup were male. There was a 70-fold increase in the risk for developing hiccup in the aripiprazole/benzodiazepine intake condition versus all other conditions, and it further increased if limiting to the male sex., Limitations: The retrospective nature of the study was its limitation., Conclusions: Hospitalized psychiatric patients on both aripiprazole and benzodiazepines may be at significant risk of hiccup. This clinical awareness could lead to antipsychotic and/or benzodiazepine discontinuation or switch or to the addition of calcium channel blocker inhibitors.

Pathological gambling behaviour is a side effect of dopaminergic drugs used in Parkinson's disease, but has seldom been reported with selective serotonin reuptake inhibitors. A 58-years-old woman with somatisation disorder since the age of 20 and recent-onset major depression (at 54 years) received 40 mg/day intravenous citalopram, thereafter switching to the same dose of oral citalopram to treat her comorbid psychiatric disorders after showing poor response to paroxetine for one year. Her anxious and depressive symptoms were moderately reduced after 7 months of oral citalopram, but simultaneously, the patient admitted gambling. We gradually discontinued citalopram and introduced pregabalin and alprazolam; this was followed by a reduction of gambling compulsions, but the somatisation and depressive symptoms did not further improve. Pathological gambling may be mediated by an interplay of 5-HT1A serotonergic and D2 dopaminergic mechanisms. Citalopram affects both these mechanisms in areas that were shown to be involved in gambling behaviour, but while dopaminergic effects of citalopram appear to be consistent with the induction of gambling, its serotonergic mechanisms are rather inconsistent. In our patient, mood destabilisation induced by citalopram may have contributed to the first onset of pathological gambling.

Objectives: To review the role of Wnt pathways in the neurodevelopment of schizophrenia., Methods: SYSTEMATIC PUBMED SEARCH, USING AS KEYWORDS ALL THE TERMS RELATED TO THE WNT PATHWAYS AND CROSSING THEM WITH EACH OF THE FOLLOWING AREAS: normal neurodevelopment and physiology, neurodevelopmental theory of schizophrenia, schizophrenia, and antipsychotic drug action., Results: Neurodevelopmental, behavioural, genetic, and psychopharmacological data point to the possible involvement of Wnt systems, especially the canonical pathway, in the pathophysiology of schizophrenia and in the mechanism of antipsychotic drug action. The molecules most consistently found to be associated with abnormalities or in antipsychotic drug action are Akt1, glycogen synthase kinase3beta, and beta-catenin. However, the extent to which they contribute to the pathophysiology of schizophrenia or to antipsychotic action remains to be established., Conclusions: The study of the involvement of Wnt pathway abnormalities in schizophrenia may help in understanding this multifaceted clinical entity; the development of Wnt-related pharmacological targets must await the collection of more data.

Study Objective: To assess acute efficacy and safety of 9.75 mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation., Design: Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation. Partial analysis of blood levels of the administered drug to correlate with clinical response., Setting: Acute psychiatric care wards in a single university hospital., Patients: A total of 201 acutely agitated patients (79 with schizophrenia and 122 with bipolar disorder I)., Intervention: Aripiprazole 9.75 mg IM injection., Measurements and Main Results: We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation/Calmness Evaluation Scale (ACES), and the Clinical Global Impressions scale (CGI). Assessments were conducted 30, 60, 90, and 120 minutes and 24 hours after the first injection for PANSS-EC and ACES, and 2, 4, 6, and 24 hours for CGI. Response was at least a 40% decrease in PANSS-EC scores. We measured serum aripiprazole and dehydroaripiprazole levels in a subsample. IM aripiprazole significantly improved clinical measures. PANSS-EC improved progressively, starting after 30 minutes. ACES improved after 90 minutes and continued thereafter. Effects were sustained, with steadily decreasing CGI scores, until the 24th hour. Response rate was 83.6% after 2 hours, but with repeat injections, it rose to over 90% with no differences among diagnostic groups. Although there were gender differences in the response to individual PANSS-EC items, the responses were similar overall. Neither clinical monitoring nor patient reporting revealed any side effects. No therapeutic window was identified, and levels did not correlate with any clinical measure., Conclusion: Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia. Our results compare favorably to double-blind trials, probably due to higher expectations in trials involving no placebo arm. Absence of side effects could be related to the short observation time., (© 2013 Pharmacotherapy Publications, Inc.)

A Caucasian, male, young adult with recurrent agitated depression and suicidal ideation received lithium and oral olanzapine. His white blood cell count was normal at that time. Due to unsatisfactory response, he received 4 mg/day risperidone. While symptoms improved, leukopenia emerged, specifically directed towards neutrophils. Upon risperidone discontinuation, white blood cell count returned to reference values within 1 week. As symptom control was satisfactory, we attempted no risperidone rechallenge. Accurate blood testing must accompany atypical antipsychotic drug administration since blood dyscrasias are always possible with these drugs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A young woman with bipolar I disorder and comorbid catatonia on enteral nutrition from several months, developed a form of near-lethal catatonia with weight loss, pressure sores, muscle atrophy, electrolyte imbalance, and depression of vital signs. A compulsory treatment was necessary, and informed consent was obtained from her mother for electroconvulsive therapy (ECT). After 7 ECT sessions, the patient recovered and resumed feeding. ECT may save the life of a patient with catatonia provided that legal obstacles are overcome. Clinicians should carefully evaluate patients with near-lethal catatonia, taking into account the risk of pulmonary embolism and other fatal events. The medical-legal issues, which vary across state regulations, should be addressed in detail to avoid unnecessary and potentially harmful delay in intervention.

Background and Objectives: Current liquid chromatographic tandem mass spectrometry (LC-MS/MS) methods to measure serum levels of aripiprazole (Ar) and dehydroaripiprazole (DHAr) are sensitive, but difficult to use in a hospital context. We aimed to develop a rapid LC-MS/MS method allowing reliable level measurement in the presence of co-administered drugs, withdrawing samples from 22 patients with acute agitation receiving 9.75 mg aripiprazole IM injection., Method: We developed a sensitive and selective HPLC-MS/MS method to measure serum Ar and DHAr levels in a hospital laboratory, requiring minimal sample preparation and inferior sample volume compared to previous LC-MS/MS methods. Analytes were separated on a reversed-phase HPLC (run-time, 10 min). A triple quadrupole tandem mass spectrometer was used for quantitative analysis in positive mode by a multiple reaction monitoring. Samples were drawn 2, 4, 6, and 24h post-injection., Results: Calibration curves (2-1000 ng/mL for Ar and 3.5-500 ng/mL for DHAr) were linear, with mean correlation coefficient >0.9998. Within- and between-day precision and accuracy were within 10%. Mean recovery was 95.2 ± 4.5% for Ar and 97.6 ± 7.2% for DHAr. Ar and DHAr peaks were not affected by other co-administered psychotropic drugs., Conclusion: Our method measured Ar and DHAr concentrations reliably, simply and rapidly without employing many reagents, as currently existing methods., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Congestive heart failure (CHF) and hypertension are prevalent diseases with high mortality and morbidity rates. Depression and anxiety are frequently associated with cardiovascular diseases. This observational cross-sectional study assessed depression, anxiety, suicidality, and quality of life in 240 patients with CHF (with or without hypertension) or hypertension (without CHF)., Method: Subjects were evaluated between June 2005 and June 2007 using the Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Medical Outcomes Study 36-item Short-Form Health Survey (both physical component score and mental component score), and Satisfaction With Life Scale (SWLS). Patients with CHF were assigned a New York Heart Association functional classification., Results: The CHF patients had higher scores on the depressive factor and the HARS and higher suicidality. Furthermore, they had lower scores on the physical component score, higher scores on the mental component score, and lower scores on the SWLS. Depressive symptom level was a significant predictor of lower physical health (P = .012), whereas anxiety was a significant predictor of satisfaction with life (P = .002). CHF compared to hypertension was a predictor of higher mental health as measured with the mental component score and lower satisfaction with life. Higher anxiety predicted lower satisfaction with life both in patients with CHF and with hypertension., Conclusions: Anxiety and depressive symptoms and cardiovascular disease were frequently associated. Screening for anxiety and depression in cardiovascular patients may be crucial.

The goals of this study were to assess the validity and usefulness of a new scale and to assess disability in a sample of patients with chronic daily headache. Participants were a convenience sample of 61 adult outpatients admitted to the Department of Medical Sciences of the Sant'Andrea Hospital in Rome, between September 2007 and May 2008. Inclusion criteria were, a diagnosis of chronic daily headache (illness duration >5 years). Patients were administered the Beck Hopelessness Scale (BHS), a specific section of the Mini-International Neuropsychiatric Interview (MINI) assessing suicidal intent, the Gotland Male Depression Scale (GMDS), and a scale devised to measure the degree of disability caused by the headache [Italian Perceived Disability Scale (IPDS)]. Analyses indicated that the IPDS had good internal consistency (Cronbach alpha = 0.93; average inter-item correlation = 0.40), and good convergent validity, with moderate to strong associations with measures assessing emotional distress (BHS, r = 0.47; P < 0.0001; GMDS, r = 0.72; P < 0.001). A single-item, logistic regression analysis indicated that the IPDS is able to predict suicide intent (Wald chi(2) = 5.04; P < 0.05) in chronic daily headache patients. The IPDS is a brief instrument that is useful for comparisons with other chronic illnesses, and it may be used both for basic research and clinical applications when screening for comorbidity with emotional distress and disorders.