Quetiapine Abuse Fourteen Years Later: Where Are We Now? A Systematic Review.

Background: Quetiapine, an atypical antipsychotic endowed with weak dopamine antagonist, potent 5-HT2A-blocking, partial 5-HT1A-agonist, anti-H1 histamine, adrenolytic, and sigma1 receptor agonist activities, since an original 2004 report is increasingly misused. Although some of its pharmacodynamics might explain some motives for voluptuary use, most of its actions are directed at setting-off those motives. Hence, it is possible that its popularity in special populations is due to the fact that the unpleasant or unwanted effects of addiction substances are somehow soothed by quetiapine. Currently, quetiapine is tested in substance use disorders, showing some promise, but it is likely to be misused in certain contexts. Objectives: To review the evidence for the use of quetiapine as addiction substance and investigate the characteristics of populations involved in such addiction. Methods: A systematic review of literature on various databases retrieved on September 7, 2018 87 records to comment. Results. We reviewed the evidence for quetiapine's addictive potential in the light of its pharmacodynamics properties and presented two cases of recreational quetiapine use, by a 35-year old male patient with past addictive behavior and by a 50-year-old woman with major depressive disorder and conversion disorder. We found quetiapine to be abused mainly by addict populations and people with law involvement. Conclusions/Importance: There is no reason to include quetiapine among regulated substances, but monitoring of its use in selected populations is warranted. Psychiatrists and physicians working in the penitentiary system should be aware of the addictive potential of quetiapine and adopt measures restricting its use.

Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate.

BACKGROUND: Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia. OBJECTIVE: The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI. METHOD: Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point. RESULTS: Longer treatment time with LAIs (p < .001), lower number of oral drugs (p < .001), and hospitalisations (p = .002) before LAI introduction, and shorter duration of illness (p = .038) predicted better Global Assessment of Functioning scores in the whole sample (R2  = 0.337). CONCLUSION: Early administration and longer duration of ARI or PAL treatments could play a significant role in improving global functioning of patients with schizophrenia and schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations.

Erectile dysfunction in patients taking psychotropic drugs and treated with phosphodiesterase-5 inhibitors.

OBJECTIVES: The aim of this study was to assess the prevalence of patients with Erectile Dysfunction (ED) receiving psychotropic drugs, the impact of these drugs on hormonal profile, and the efficacy of PDE5-i in these patients. MATERIALS AND METHODS: We recruited 1872 patients referring for ED to our Andrology Unit. Assessment included serum testosterone, gonadotropins, TSH, prolactin, and PSA, and the IIEF-5 questionnaire for ED diagnosis. Inclusion criteria were age 21-75 years and IIEF-5 total score ≤ 21; exclusion criteria included hypogonadism, diabetes mellitus, previous prostatectomy, other medication intake, and ED diagnosis prior to psychotropic drug treatment. Efficacy was rated with the IIEF-5 (remission: total score ≥ 22). RESULTS: The prevalence of ED patients treated with psychotropic drugs since ≥ 3 months was 9.5% (178/1872), subdivided according to the drugs used into: Group A, 16 patients treated with atypical antipsychotics (9.0%); Group B, 55 patients with benzodiazepines (30.9%); Group C, 33 patients with antidepressant drugs (18.5%); and Group D, 74 patients with multiple psychotropic drugs (41.6%). Patients in Group A were significantly younger than other groups (p < 0.05). The hormonal profile presented only higher prolactin level in patients treated with antipsychotics, alone or in combination (p < 0.05). Overall, 146 patients received PDE5-i. Remission rate, after three months of treatment, was significantly higher in Group B compared to C and D groups (p < 0.05). CONCLUSIONS: A substantial portion of patients receiving psychotropic drugs show ED. Sexual performance in these patients benefits from PDE5-i. Age, effects of psychiatric disorders, psychotropic drugs, and PDE5-i treatment modality accounted for variability of response in this sample.

Depressive symptoms, temperament/character, and attention deficit/hyperactivity disorder traits in medical students seeking counseling.

BACKGROUND: To investigate depressive symptoms, temperament, and attention deficit/hyperactivity disorder traits in medical students, comparing those who sought psychological counseling with those who did not seek it. SUBJECTS AND METHODS: We assessed 49 students seeking counseling (mean age=24.4 years, SD=4.07) and 49 noncounseling controls (mean age=21.7 years, SD=2.6). Participants were assessed for depressive symptoms with the Beck Depression Inventory-II, for temperament/character dimensions using the Temperament and Character Inventory-Revised, and for attention deficit/hyperactivity symptoms using the Adult ADHD Self-Report Scale. RESULTS: Counseling-seeking students were more likely to have attention deficit/hyperactivity symptoms, scored higher on the Beck Depression Inventory-II and on the Temperament and Character Inventory-Revised Harm avoidance, and lower on the Temperament and Character Inventory-Revised Self-Directedness, compared to controls. CONCLUSIONS: Medical students applying for counseling should be carefully assessed for depressive symptoms, attention deficit/hyperactivity symptoms, and temperament characteristics; depressive and attention deficit/hyperactivity symptoms could be the focus of counseling interventions.

Functional Magnetic Resonance Imaging Correlates of First-Episode Psychoses during Attentional and Memory Task Performance.

BACKGROUND: The nature of the alteration of the response to cognitive tasks in first-episode psychosis (FEP) still awaits clarification. We used activation likelihood estimation, an increasingly used method in evaluating normal and pathological brain function, to identify activation changes in functional magnetic resonance imaging (fMRI) studies of FEP during attentional and memory tasks. METHODS: We included 11 peer-reviewed fMRI studies assessing FEP patients versus healthy controls (HCs) during performance of attentional and memory tasks. RESULTS: Our database comprised 290 patients with FEP, matched with 316 HCs. Between-group analyses showed that HCs, compared to FEP patients, exhibited hyperactivation of the right middle frontal gyrus (Brodmann area, BA, 9), right inferior parietal lobule (BA 40), and right insula (BA 13) during attentional task performances and hyperactivation of the left insula (BA 13) during memory task performances. CONCLUSIONS: Right frontal, parietal, and insular dysfunction during attentional task performance and left insular dysfunction during memory task performance are significant neural functional FEP correlates.

The Clinical and Radiological Examination of Acute Intimate Partner Violence Injuries: A Retrospective Analysis of an Italian Cohort of Women.

BACKGROUND: Intimate partner violence (IPV) is the most frequent type of violence against women. We compared clinical and radiological IPV characteristics to stranger assault (SA). METHODS: We retrospectively identified 123 women with IPV from court reports and matched them to 124 SA. Clinical and radiological characteristics were evaluated by testing their sensitivity, specificity, positive and negative predictive value for IPV, and the strength of their association with IPV. RESULTS: IPV women referred with more delay to the emergency department (ED), had more ED accesses, and showed more mismatch between reports to the triage and disclosures to the ED physician. They also displayed more head, neck, and face injuries, and new-plus-old fractures. CONCLUSION: The identification of specific features may help ED physicians to suspect IPV.

Functional Neuroimaging in Psychopathy.

BACKGROUND AND AIM: Psychopathy is associated with cognitive and affective deficits causing disruptive, harmful and selfish behaviour. These have considerable societal costs due to recurrent crime and property damage. A better understanding of the neurobiological bases of psychopathy could improve therapeutic interventions, reducing the related social costs. To analyse the major functional neural correlates of psychopathy, we reviewed functional neuroimaging studies conducted on persons with this condition. METHODS: We searched the PubMed database for papers dealing with functional neuroimaging and psychopathy, with a specific focus on how neural functional changes may correlate with task performances and human behaviour. RESULTS: Psychopathy-related behavioural disorders consistently correlated with dysfunctions in brain areas of the orbitofrontal-limbic (emotional processing and somatic reaction to emotions; behavioural planning and responsibility taking), anterior cingulate-orbitofrontal (correct assignment of emotional valence to social stimuli; violent/aggressive behaviour and challenging attitude) and prefrontal-temporal-limbic (emotional stimuli processing/response) networks. Dysfunctional areas more consistently included the inferior frontal, orbitofrontal, dorsolateral prefrontal, ventromedial prefrontal, temporal (mainly the superior temporal sulcus) and cingulated cortices, the insula, amygdala, ventral striatum and other basal ganglia. CONCLUSIONS: Emotional processing and learning, and several social and affective decision-making functions are impaired in psychopathy, which correlates with specific changes in neural functions.

Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature.

OBJECTIVE: The purpose of this literature database search-based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5-HT3 antagonists in the treatment of obsessive-compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials. DESIGN: The PubMed database has been searched for papers on 5-HT3 antagonists and OCD in humans and for animal models of OCD and 5-HT3 receptors. RESULTS: Of the clinically tested 5-HT3 receptor antagonists, ondansetron has been used to treat OCD in five therapeutic studies, whereas granisetron only in one recent trial. Both showed some efficacy in open studies and superiority to placebo in double-blind studies, along with fair safety. No animal OCD model directly implicated 5-HT3 receptors. CONCLUSIONS: Overall, results indicate some utility, but the available literature is too scanty to allow for valid conclusions to be drawn. The mismatch between animal models of obsessive-compulsive disorder and clinical data with 5-HT3 antagonists needs more clinical data to ensure that it is not an artefact.

Neurodevelopment in schizophrenia: the role of the wnt pathways.

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.

Epilepsy and brain injury: a case report of a dramatic neuropsychiatric vicious circle.

PRIMARY OBJECTIVE: Early treatment of epilepsy is warranted to avoid possible severe consequences. This study aimed to assess the value of treatment in a patient who developed epilepsy after major brain surgery. DESIGN: Case description. A 51 years-old man had a history of putative petit mal seizures since adolescence and left frontotemporal lobectomy after a major traffic accident at age 17. He subsequently developed quickly generalizing partial complex seizures, associated with severe behavioural alterations and personality changes; the condition was left untreated. A further seizure-related loss of consciousness led to another traffic accident at age 47. METHODS AND PROCEDURES: The patient was administered 200 mg/day topiramate, 600 mg/day quetiapine, 1000 mg/day valproate, 1200 mg/day gabapentin and 800 mg/day carbamazepine. MAIN OUTCOMES AND RESULTS: The instituted anti-epileptic treatment reduced seizure frequency and severity, but did not affect psychiatric symptomatology, which even worsened. An association between anti-epileptic drugs with mood stabilizing properties and an atypical anti-psychotic dramatically improved psychiatric symptoms, but did not prevent the patient from needing long-term healthcare. CONCLUSIONS: Long-term untreated epilepsy may expose to accident proneness and further psychiatric deterioration. Early diagnosis and treatment of epilepsy may help in avoiding a potentially lethal vicious circle.

Prevention of relapse with maintenance electroconvulsive therapy in elderly patients with major depressive episode.

OBJECTIVES: To evaluate the effectiveness and safety of maintenance electroconvulsive therapy (mECT) in elderly patients with treatment-resistant Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode. METHODS: Seven elderly patients with treatment-resistant major depressive episode were treated with a complete ECT cycle. Thereafter, they received one monthly ECT session as maintenance for 1 year. Response to treatment was defined as at least a 50% drop from baseline on the Hamilton Depression Rating Scale (HamD) and remission as not meeting criteria for major depression, a HamD score of 7 or less, and Clinical Global Impressions-Severity of Illness score of 1. We compared their response with the response of 7 elderly patients with treatment-resistant major depression who were treated with a full cycle of ECT but did not receive mECT (non-mECT). We compared the 2 groups for the number of relapses or recurrences of major depressive episodes after remission was achieved; a relapse or a recurrence occurred when HamD scores were 14 or higher, or when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision major depressive episode criteria were met, or when Clinical Global Impressions-Severity of Illness score was 3 or higher and increased by at least 2 points from response/remission. RESULTS: The mECT group (4 women and 3 men; mean age, 73 years) had significantly less mean relapses/recurrences (0 vs 1.57) and hospitalizations (0 vs 1) and received less drug treatment than the nonMECT group (similar for age and sex composition) during the 12-month follow-up period. All patients with mECT improved during treatment and did not relapse. CONCLUSIONS: Maintenance ECT protected elderly patients from recurrent depressive episodes from relapsing/recurring more than standard ECT.

Effectiveness of electroconvulsive therapy in a patient with a treatment-resistant major depressive episode and comorbid body dysmorphic disorder.

A 24-year-old man experiencing comorbid body dysmorphic disorder since age 16 years, complicated in recent months by a major depressive episode with psychotic features, showed resistance to various drug and psychotherapy combinations. We suggested electroconvulsive therapy (ECT) to overcome treatment resistance. After 1 ECT cycle, mood and anxiety symptoms improved significantly, delusional interpretations and ideas of reference subsided, and dysmorphophobic symptoms improved as well. Six months later, the patient was doing well with a mood stabilizer/antipsychotic combination. Electroconvulsive therapy may improve symptoms of comorbid body dysmorphic disorder along with mood improvement in treatment-resistant depressive disorder.

Electroconvulsive therapy in a man with comorbid severe obesity, binge eating disorder, and bipolar disorder.

A 41-year-old man with comorbid binge-eating disorder, severe obesity, and bipolar disorder since the age of 20 years, resistant to drug and psychotherapy combinations, worsened progressively. Relentless weight gain forced him to immobility and dependence on others. He was hospitalized for a mixed-mood episode with anxiety, mystical delusions, and auditory hallucinations. To overcome treatment resistance, we suggested electroconvulsive therapy. After 1 electroconvulsive therapy cycle, psychological symptoms promptly improved. He received clozapine and lithium. After 2 years, he reached normal weight and fair psychopathological compensation.

Structural neuroimaging in patients with panic disorder: findings and limitations of recent studies.

BACKGROUND: Panic disorder, a relatively common anxiety disorder, is often associated to agoraphobia and may be disabling. Its neurobiological underpinnings are unknown, despite the proliferation of models and hypotheses concerning it; investigating its correlates could provide the means for better understanding its pathophysiology. Recent structural neuroimaging techniques may contribute to the identification of possible brain morphological alterations that could be possibly related to the clinical expression of panic disorder. METHODS: Through careful major database searches, using terms keen to panic, agoraphobia, structural magnetic neuroimaging and the like, we identified papers published in peer-review journals and reporting data on the brain structure of patients with panic disorder. Included papers were used comparatively to speculate about the nature of reported brain structural alterations. RESULTS: Anxiety, which is the core feature of the disorder, correlates with the function of the amygdala, which showed a smaller volume in patients, as compared to healthy subjects. Data also showed a volumetric decrease of the anterior cingulate along with increased fractional anisotropy, and increase of some brainstem nuclei, particularly of the rostral pons. Other structures with reported volumetric correlates of panic disorder are the hippocampus and the parahippocampal cortices, the insula, the putamen, and the pituitary gland. Volumetric changes in the anterior cingulate, frontal, orbitofrontal, insular, and temporal cortices have also been described in structural neuroimaging studies. Major methodological limitations are considered in context. CONCLUSIONS: Several data point to the existence of structural neuroanatomical alterations in panic disorder, consisting in significant volumetric reductions or increases in different brain areas. White matter alterations were shown also in the only diffusion tensor imaging study performed to date. Available data do not allow us to conclude about the possible progression of these alterations.

[Olanzapine in manic/mixed patients with or without substance abuse]. / Olanzapina in pazienti maniacali o misti con o senza abuso di sostanze.

AIM: To evaluate the efficacy of olanzapine in patients in their manic/mixed phase with or without comorbidity with substance abuse/dependence disorder. METHODS: In this observational, controlled, prospective study, 60 patients with a DSM-IV-TR diagnosis of bipolar disorder, manic/mixed episode (30 patients with and 30 patient without comorbidity with a substance abuse/dependence disorder) were treated with olanzapine, evaluated at discharge, and followed-up for 8 weeks. Efficacy of olanzapine was assessed by comparing the proportion of responders (an at least 50% drop in Young Mania Rating Scale [YMRS] score from baseline) and remitters (YMRS ≤ 12 and Hamilton Depression Rating Scale [HAM-D] ≤ 8) in both groups. Craving and days of abuse/use were assessed with Visual Analogue Scale (VAS) and Time-line Follow-Back (TLFB), respectively. RESULTS: Differences in response and remission percentages were statistically not significant at discharge and during follow-up. A reduction of days of abuse has been observed in the drug-abuse group, while craving was only slightly decreased. DISCUSSION: These results suggest that olanzapine is effective in both groups and its efficacy in reducing the days of abuse appears to be independent from its action on craving.

[Functional neuroimaging of the amygdala: the response to threatening and phobogenic stimuli]. / Neuroimaging funzionale dell'amigdala: la risposta a eventi minacciosi o fobigeni.

Recent functional neuroimaging studies show that the amygdala has a central role in threat evaluation, in response to conditioned and unconditioned stimuli, in fear learning and fear extinction. The amygdala is involved in the pathophysiology of phobias and anxiety. In this review we critically examine the main findings of functional neuroimaging studies reporting data on the amygdala. Findings suggest that the response of the amygdala to threatening stimuli is mainly modulated by the infralimbic and prefrontal cortices, which inhibit activation of the amygdala (top-down inhibition), and by the hippocampus, the function of which is related to stimulus learning. The activity of the amygdala is modulated by various factors, like stimulus type and origin, emotion triggered by stimulus perception, and attention. The neural network comprising the amygdala and the frontal cortex is involved not only in top-down inhibition, but also in the emotional perception of facial expressions. This network also includes the thalamic pulvinar, which is densely interconnected with the amygdala, directly or indirectly, and which is activated by emotional face recognition of scary fear. Both top-down inhibition mechanisms and emotional face recognition are altered in anxiety disorders, particularly in specific and social phobia, resulting in reduced amygdalar activity inhibition after anxiety - or fear - inducing stimulus perception. Future functional neuroimaging studies will be able to provide new insights of normal and altered neurophysiology of the amygdala.

Functional neuroimaging in specific phobia.

Specific phobias (SPs) are common, with lifetime prevalence estimates of 10%. Our current understanding of their pathophysiology owes much to neuroimaging studies, which enabled us to construct increasingly efficient models of the underlying neurocircuitry. We provide an updated, comprehensive review and analyze the relevant literature of functional neuroimaging studies in specific phobias. Findings are presented according to the functional neuroanatomy of patients with SPs. We performed a careful search of the major medical and psychological databases by crossing SP with each neuroimaging technique. Functional neuroimaging, mostly using symptom provocation paradigms, showed abnormal activations in brain areas involved in emotional perception and early amplification, mainly the amygdala, anterior cingulate cortex, thalamus, and insula. The insula, thalamus and other limbic/paralimbic structures are particularly involved in SPs with prominent autonomic arousal. Emotional modulation is also impaired after exposure to phobic stimuli, with abnormal activations reported for the prefrontal, orbitofrontal and visual cortices. Other cortices and the cerebellum also appear to be involved in the pathophysiology of this disorder. Functional neuroimaging identified neural substrates that differentiate SPs from other anxiety disorders and separate SP subtypes from one another; the results support current Diagnostic and Statistical Manual of Mental Disorders, 4th edition-Text Revision (DSM-IV-TR) diagnostic subtyping of SPs. Functional neuroimaging shows promise as a means of identifying treatment-response predictors. Improvement in these techniques may help in clarifying the neurocircuitry underlying SP, for both research and clinical-therapeutic purposes.

The wnt pathway in mood disorders.

OBJECTIVES: To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in the action of drugs used to treat these disorders. METHODS: We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in their treatment. Papers were selected on the basis of their content and their data used for discussion. RESULTS: Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive disorders. CONCLUSIONS: Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood disorders.

Successful and rapid response to electroconvulsive therapy of a suicidal patient with comorbid bipolar I disorder and histrionic personality disorder.

A woman with bipolar disorder I, histrionic personality disorder, and suicidal ideation with repeated suicide attempts, who had been treated for 2 years with mood stabilizers, antipsychotics, and benzodiazepines, received a total of 8 bitemporal-biparietal electroconvulsive therapy sessions. Her suicidal ideation and self-harm behavior disappeared immediately after the first session and her psychopathology soon after. This supports the existence of a relatively independent suicidal syndrome and confirms data on its immediate responsiveness to electroconvulsive therapy. Electroconvulsive therapy must not be long withheld from patients with such characteristics to reduce unnecessary sufferance and suicidality.