Aripiprazole IM depot as an option for the treatment of bipolar disorder.

Introduction: Long-acting injectable (LAI) antipsychotic drugs are developed to reduce daily intake need and to overcome treatment non-adherence. Aripiprazole IM depot refers to two long-acting aripiprazole formulations, once monthly monohydrate (AOM) and aripiprazole lauroxil. AOM has been approved for schizophrenia since 2012 and for bipolar disorder since 2017. Aripiprazole lauroxil is approved for schizophrenia, not for bipolar disorder.Areas covered: To assess the effect of AOM in bipolar disorder, the authors searched PubMed and ClinicalTrials.gov for randomized trials using AOM in patients with bipolar disorder. Included were four studies covering efficacy, functioning, quality of life, and safety/tolerability. Studies lasted 12 months.Expert opinion: AOM reduced symptoms of patients with bipolar disorder and a manic episode, increased functioning and quality of life, and protected from recurrence of manic episodes. It proved to be safe/tolerable, with only akathisia occurring in ≥10% of cases and more frequently than with placebo. However, there were only 143 patients receiving AOM in the considered studies. Included studies were backed in their conclusions by other literature, but they come from 2017-2018. No studies are expected or planned in the near future. Aripiprazole lauroxil has not applied for approval in bipolar disorder and there is no sign it will.

PON1 polymorphisms can predict generalized anxiety and depressed mood in patients with multiple chemical sensitivity.

Background: Multiple chemical sensitivity (MCS) is a chronic condition with somatic, cognitive and affective symptoms that follow contact with chemical agents at usually non toxic concentrations. We aimed to assess the role of genetic polymorphisms involved in oxidative stress on anxiety and depression in MCS. Materials & methods: Our study investigated the CAT rs1001179, MPO rs2333227, PON1 rs662 and PON1 rs705379 polymorphisms in MCS. Results: The AG genotype of the PON1 rs662 and the TT and CT genotypes of the PON1 rs705379 were involved in anxiety and depression. Discussion: These results are in line with existing evidence of PON1 involvement in MCS and suggest a further role of this gene in the exhibition of anxiety and depression in this disease.

Mixed Features in Depression: The Unmet Needs of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.

The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition introduced the specifier "with mixed features" including 3 or more nonoverlapping typical manic symptoms during a major depressive episode in bipolar disorder type I or II or unipolar major depressive disorder. Excluding overlapping excitatory symptoms, which are frequently observed in mixed depression, leaves many patients with mixed depression undiagnosed. As a consequence, alternative diagnostic criteria have been proposed, claiming for the inclusion in the rubric of mixed features the following symptoms: psychomotor agitation, mood lability, and aggressiveness. A deeper diagnostic reconsideration of mixed features in depression should be provided by the new nosologic classification systems.

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.

Long-Acting Injectable (LAI) Aripiprazole Formulations in the Treatment of Schizophrenia and Bipolar Disorder: a Systematic Review.

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.

Brain Stimulation in Obsessive-Compulsive Disorder (OCD): A Systematic Review.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a highly prevalent, severe, and chronic disease. There is a need for alternative strategies for treatment-resistant OCD. OBJECTIVE: This review aims to assess the effect of brain stimulation techniques in OCD. METHODS: We included papers published in peer-reviewed journals dealing with brain stimulation techniques in OCD. We conducted treatment-specific searches for OCD (Technique AND ((randomized OR randomised) AND control* AND trial) AND (magnetic AND stimulation OR (rTMS OR dTMS)) AND (obsess* OR compuls* OR OCD)) on six databases, i.e., PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials and ClinicalTrials.gov for possible additional results. RESULTS: Different add-on stimulation techniques could be effective for severely ill OCD patients unresponsive to drugs and/or behavioural therapy. Most evidence regarded deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), while there is less evidence regarding transcranial direct current stimulation (tDCS), electroconvulsive therapy, and vagus nerve stimulation (for these last two there are no sham-controlled studies). Low-frequency TMS may be more effective over the supplementary motor area or the orbitofrontal cortex. DBS showed best results when targeting the crossroad between the nucleus accumbens and the ventral capsule or the subthalamic nucleus. Cathodal tDCS may be better than anodal in treating OCD. Limitations. We had to include methodologically inconsistent underpowered studies. CONCLUSION: Different brain stimulation techniques are promising as an add-on treatment of refractory OCD, although studies frequently reported inconsistent results. TMS, DBS, and tDCS could possibly find some use with adequate testing, but their standard methodology still needs to be established.

Drug Treatment of Trichotillomania (Hair-Pulling Disorder), Excoriation (Skin-picking) Disorder, and Nail-biting (Onychophagia).

BACKGROUND: Trichotillomania (TTM), excoriation (or skin-picking) disorder and some severe forms of onychophagia are classified under obsessive-compulsive and related disorders. There are different interacting neurotransmitter systems involved in the pathophysiology of impulse-control disorders, implicating noradrenaline, serotonin, dopamine, opioid peptides and glutamate, hence investigators focused on drugs able to act on these transmitters. Our aim was to critically review the efficacy of the drugs employed in impulse-control disorders. METHODS: We searched for controlled drug trials to treat TTM, excoriation, and/or nail-biting six databases (PubMed, Cochrane, Scopus, CINAHL, PsycINFO/PsycARTICLES, and Web of Science), using the search strategy: (trichotillomania OR "excoriation disorder" OR "face picking" OR "skin picking" OR "hair pulling" OR onychophagia OR "nail-biting") AND drug treatment on 12 March 2018 for all databases. We followed in our method of identifying relevant literature the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: SSRIs and clomipramine are considered first-line in TTM. In addition, family members of TTM patients are often affected by obsessive-compulsive spectrum disorders. Other drugs used in the treatment of TTM are lamotrigine, olanzapine, N-Acetylcysteine, inositol, and naltrexone. CONCLUSION: The treatment of TTM, excoriation disorder and nail-biting is still rather disappointing. Conjectures made from preclinical studies and the relative pathophysiological hypotheses found poor confirmations at a clinical level. There is a need for further studies and the integration of pharmacological and psychotherapeutic. Our results point to the need of integrating personalised medicine principles in the treatment of these patients.

Suicide among Italian police officers from 1995 to 2017.

Objective: Suicide rate in police officers is higher than in the general population worldwide. This paper assesses and analyzes the trends in suicide rates of Italian police officers from 1995 to 2017, comparing these with the trends of Italian general population. METHODS: We reviewed all cases of active Italian police officers who died by suicide from 1995 through 2017 (N=271). We calculated age- and gender- specific suicide rates among police officers and the Italian general population. We carried out descriptive chi-squared analyses for categorical variables, and one-way ANOVA for continuous variables, performing a joinpoint regression to analize suicide trends. RESULTS: The mean police suicide rate was 11.78 per 100,000 individuals per year (95% CI=11.18-12.06). Joinpoint regression analyses of the period 1995-2017 showed that suicide rates of Italian police officers significantly decreased from 1995 to 2007 (annual percent change [APC]: -5.75%), followed by a period of a non-significant increase (APC: 3.9%). The period as a whole showed a non-significant decrease (APC: -1.7%). During 1995-2014, suicide rates were significantly higher among police officers vs. the age-adjusted general population (p<0.001), in male police vs. Italian male residents younger than 65 (p<0.001), and in female police vs. the female age-adjusted general population (p<0.05). CONCLUSIONS: Suicide rates among Italian police officers were significantly higher than those of the national resident population younger than 65 years. Annual suicide rate trends among Police showed a significant reduction in the period 1995-2007 followed by a stable trend until 2017. The entire period 1995-2017 showed a non-significant decreasing trend.

Evolution of forensic psychiatry in Italy over the past 40 years (1978-2018).

In Italy, following the closure of psychiatric hospitals in 1978 and the release of psychiatric patients into community care, there was a mismatch between common psychiatric patients and the convicted mentally ill who were sentenced to serve in state forensic psychiatric hospitals. The recent closure of such structures following the Prime Minister's Decree of April 1, 2008, fostered the need to create new structures. These are called "REMS," and they are based in the community and led by psychiatrists and healthcare staff who may rely on the collaboration of public security staff. This act completed a course of progressive deinstitutionalization of all psychiatric patients. However, some problems remain, and persons regarded as "partially mentally disabled" at the time of crime perpetration must serve part of their sentence in prison and the rest in the aforementioned structures or in psychiatric rehabilitation communities, depending on their claimed "social dangerousness." Psychiatric services now face the ambiguity of treating persons who are considered dangerous by court orders, while the civil law criteria for involuntary hospitalization is based only on the need of care. The complete closure of forensic hospitals may be considered a decisive step forward in the humanization of society, but there are still some issues to address to make it work better. The implementation of multidisciplinary teams and effective psychotherapy, psychoeducational, and rehabilitation interventions can help.

Placebo Effect in Obsessive-Compulsive Disorder (OCD). Placebo Response and Placebo Responders in OCD: The Trend Over Time.

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.

Psychopharmacological Treatment of Obsessive-Compulsive Disorder (OCD).

BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with affective and cognitive symptoms causing personal distress and reduced global functioning. These have considerable societal costs due to healthcare service utilization. OBJECTIVE: Our aim was to assess the efficacy of pharmacological interventions in OCD and clinical guidelines, providing a comprehensive overview of this field. METHODS: We searched the PubMed database for papers dealing with drug treatment of OCD, with a specific focus on clinical guidelines, treatments with antidepressants, antipsychotics, mood stabilizers, off-label medications, and pharmacogenomics. RESULTS: Prolonged administration of selective serotonin reuptake inhibitors (SSRIs) is most effective. Better results can be obtained with a SSRI combined with cognitive behavioral therapy (CBT) or the similarly oriented exposure and response prevention (ERP). Refractory OCD could be treated with different strategies, including a switch to another SSRI or clomipramine, or augmentation with an atypical antipsychotic. The addition of medications other than antipsychotics or intravenous antidepressant administration needs further investigation, as the evidence is inconsistent. Pharmacogenomics and personalization of therapy could reduce treatment resistance. CONCLUSIONS: SSRI/clomipramine in combination with CBT/ERP is associated with the optimal response compared to each treatment alone or to other treatments. New strategies for refractory OCD are needed. The role of pharmacogenomics could become preponderant in the coming years.

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.

How do recruits and superintendents perceive the problem of suicide in the Italian State Police?

BACKGROUND: Suicide in international police is 2-3-fold that of the general population. Risk factors include suicidal ideation, diagnosis of mood or post-traumatic stress disorders, family/psychological problems, suffered abuse, alcohol use, service suspension, and stigma. A false stigma-related myth is to believe that suicide does not cause concern within military settings. METHODS: We administered post-training to 6103 Italian Police workers a 30-item questionnaire to assess the perception of suicidal phenomena. We conducted descriptive statistics, principal component analysis, and analyses of variance of data. RESULTS: We identified seven factors, i.e., health and environmental risk factors; need for new preventive interventions; emotional reaction to suicide; negation, indifference and minimization; utility of current preventive interventions; risk related to personal factors; intervention difficulties. CONCLUSIONS: The questionnaire showed content validity and consistency in investigating perceptions about suicide in the State Police. Data synthesis showed a mature approach and appropriate perception of the suicide problem on behalf of Italian State Police workers.

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.

Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex in depressive episodes of patients with major depressive disorder, bipolar disorder I, and major depressive with alcohol use disorders.

BACKGROUND: Dorsolateral prefrontal cortex (DLPFC) is critically involved in mood and alcohol use disorders. OBJECTIVE: We aimed to investigate the safety of intervention with add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS) and between-group differences in treatment response in patients with different types of depressive episodes, including major depressive episodes in the course of major depressive disorder (MDD), bipolar disorder, type I (BD-I), and MDD with alcohol use disorder (MDAUD). METHODS: We conducted a 6-month open-label study, involving 82 patients with DSM-5 Depressive Episode. Of these, 41 had diagnosis of MDD, 20 BD-I, and 21 MDAUD. All patients received standard drug treatment and add-on dTMS over the bilateral DLPFC with left prevalence for four weeks, with five sessions in each week. We rated mood state with the Hamilton Depression Rating Scale (HDRS) at baseline, one-month, and six-month follow-up visits. RESULTS: Mean total HDRS scores dropped from 22.8 (SD = 5.9) at baseline to 10.4 (SD = 3.6) at 1 month, to 10.0 (SD = 4.5) at 6 months, while response/remission were 70.73% (N = 58) and 19.51% (N = 16) at 1 month and 76.83% (N = 63) and 32.93% (27) at 6 months, respectively, with no between-group differences. No patient experienced any side effects. CONCLUSIONS: High-frequency DLPFC dTMS was well tolerated and did not significantly differ on improvement of depression in MDD, BD-I, and MDAUD.

Neural functional correlates of empathic face processing.

OBJECTIVES: Empathy is a human trait related to the ability to share someone else's feelings, and emotional face processing is one of its measures. Functional Magnetic Resonance Imaging (fMRI) studies showed significant neural correlates of empathic face processing. We aimed to identify those brain areas most consistently involved in empathy for emotional faces. METHODS: We carried ALE meta-analysis of whole-brain data from fMRI studies during empathic face-processing tasks. We included 23 studies conducted on a total of 568 participants (247 males and 321 females, mean age 32.2 years). RESULTS: Emotional vs. control faces processing significantly correlated with activations of the left anterior cingulate cortex (BA 32), right precentral gyrus (BA 6), left amygdala, right superior frontal gyrus (BA 9), left middle occipital gyrus (BA 37), right insula (BA 13), left putamen, and left posterior cingulate cortex (BA 31). CONCLUSIONS: Empathy is a complex process correlating with bi-hemispheric cortico-limbic activations involved in emotional cue processing, self-other/same-different discrimination, perspective-taking, theory of mind, emotional arousal, and decision-making.