Mental disorders, psychopharmacological treatments, and mortality in 2150 COVID-19 Spanish inpatients.

OBJECTIVE: To determine how mental disorders and psychopharmacological treatments before and during COVID-19 hospital admissions are related to mortality. METHODS: Subjects included in the study were all adult patients with a diagnosis of COVID-19, confirmed clinically and by PCR, who were admitted to a tertiary university hospital in Badalona (Spain) between March 1 and November 17, 2020. Data were extracted anonymously from computerized clinical records. RESULTS: 2,150 subjects were included, 57% males, mean age 61 years. History of mental disorders was registered in 957 (45%). Throughout admission, de novo diagnosis of mood or anxiety, stress, or adjustment disorder was made in 12% of patients without previous history. Delirium was diagnosed in 10% of cases. 1011 patients (47%) received a psychotropic prescription during admission (36% benzodiazepines, 22% antidepressants, and 21% antipsychotics). Mortality rate was 17%. Delirium during admission and history of mood disorder were independently associated with higher mortality risk (hazard ratios, 1.39 and 1.52 respectively), while previous year's treatments with anxiolytics/hypnotics and antidepressants were independently associated with lower mortality risk (hazard ratios, 0.47 and 0.43, respectively). CONCLUSION: Mental symptoms are very common in patients hospitalized for COVID-19 infection. Detecting, diagnosing, and treating them is key to determining the prognosis of the disease and functional recovery.

Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice.

4,4'-Dimethylaminorex (4,4'-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1-60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4'-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers' co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.

New psychoactive substances: challenges for drug surveillance, control, and public health responses.

The rapid emergence since the mid-2000s of a large and diverse range of substances originally designed as legal alternatives to more established illicit drugs (pragmatically clustered and termed new psychoactive substances; [NPS]) has challenged traditional approaches to drug monitoring, surveillance, control, and public health responses. In this section of the Series, we describe the emergence of NPS and consider opportunities for strengthening the detection, identification, and responses to future substances of concern. First, we explore the definitional complexity of the term NPS. Second, we describe the origins and drivers surrounding NPS, including motivations for use. Third, we summarise evidence on NPS availability, use, and associated harms. Finally, we use NPS as a case example to explore challenges and opportunities for future drug monitoring, surveillance, control, and public health responses. We posit that the current means of responding to emerging substances might no longer be fit for purpose in a world in which different substances can be rapidly introduced, and where people who use drugs can change preferences on the basis of market availability.

Fatalities associated with NPS stimulants in the Greater Cologne area.

This study centres on the prevalence of new psychoactive substances (NPS) stimulant use, and its relevance as a cause of death amongst individuals between the ages of 12 and 35 in the greater Cologne area. An automated solid-phase extraction-liquid chromatography-tandem mass spectrometry method was developed for the determination of 97 stimulants in urine (including conventional stimulants, e.g. amphetamine and MDMA), of which 68 analytes were fully validated for quantification. Samples of urine or kidney tissue (in cases where urine was unavailable) of 268 deceased were collected, during autopsy, between January 2011 and May 2017 and analyzed. Blood (if available) was also investigated in cases where urine/kidney samples were tested positive for NPS. An intake of stimulants (including NPS stimulants) was proven in 50 cases. In 33 cases, only conventional stimulants were detected. A total of 17 cases were tested positive for NPS. Of the 17 NPS-positive cases, 13 were also tested positive for other conventional drugs of abuse (mostly amphetamine and MDMA). In six NPS-positive cases, at least three different NPS were proven to be ingested. Due to the determined blood concentrations, NPS was assigned as the leading cause of death, or of toxicological relevance, in the cause of death in only 5 cases. In two of the cases, NPS was judged to be a component of a multidrug poisoning, but of minor relevance.

Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy.

AIM: To assess the effect of psychotropic drugs on fetal behavior using four-dimensional (4D) ultrasound in the third trimester of pregnancy. METHODS: Fetal behavior was assessed using Kurjak's antenatal neurodevelopmental test (KANET) using 4D ultrasound between 28 and 36 weeks of gestation. Thirty healthy (control group) and 10 psychotropic-drug-administered pregnant (case group) women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared between the two groups. RESULTS: The total KANET score was normal (except for one fetus in the case group: total score of 9) in both groups, and there was no significant difference in the total KANET score. When individual KANET parameters were compared, no significant differences were noted in any of the eight parameters. CONCLUSION: Our results showed that there is no difference in fetal behavior between fetuses of normal pregnant women and those of psychotropic-drug-administered pregnant women in the third trimester of pregnancy. These results suggest that psychotropic drugs may not affect fetal behavioral development in utero. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the effect of psychotropic drugs on fetal neurobehavior during pregnancy.

Emerging treatments for the behavioral and psychological symptoms of dementia.

Dementia is referred to a loss of memory and decline in other mental abilities at levels critical enough to hinder performance of daily activities. It can be of several types, depending on the underlying pathophysiology. The behavioral and psychological symptoms of dementia (BPSD) are various, but the most clinically significant are depression, apathy, and anxiety. Other BPSD include agitation, aberrant motor behavior, elation, hallucinations, and alterations in sleep and appetite. About 90% of sufferers of dementia are affected by BPSD during the course of the illness. These symptoms occur in demented patients irrespective of the dementia subtype. However, there has not been significant development in the areas of disease-modifying pharmacotherapeutics for dementia. Therefore, tackling BPSD has emerged as a research avenue in the recent past. Existing antidepressants, antipsychotics, and cholinergic agents have been extensively used in the treatment of BPSD, independently and in different combinations. However, these agents have not successful in completely alleviating such symptoms. Research in this field is going on globally, but it is still limited by various factors. There is a strong need to develop new entities and test them clinically. This review focuses on emerging treatments for the management of clinically significant BPSD.

A cross-sectional examination of the prevalence of psychotropic medications for people living with dementia in Australian long-term care facilities: issues of concern.

ABSTRACTBackground:Behavioral and psychological symptoms of dementia (BPSD) are a common problem in long-term care facilities (LTC). Clinical guidelines dictate that first-line treatments for BPSD are psychosocial and behavioral interventions; if these are unsuccessful, psychotropic medications may be trialed at low doses and their effects can be monitored. METHODS: There have previously been no studies with nationally representative samples to investigate psychotropic administration in LTCs in Australia. This study determines the prevalence of psychotropic administration in a representative stratified random sample of 446 residents living with dementia from 53 Australian LTCs. Questionnaire and medical chart data in this study is drawn from a larger cross-sectional, mixed methods study on quality of life in Australian LTCs. RESULTS: It was found that 257 (58%) residents were prescribed psychotropic medications including: antipsychotics (n = 160, 36%), benzodiazepines (n = 136, 31%), antidepressants (n = 117, 26%), and anti-dementia medications (n = 9, 2%). BPSD were found to be very common in the sample, with 82% (n = 364) of participants experiencing at least one BPSD. The most prevalent BPSD were depression (n = 286, 70%) and agitation (n = 299, 67%). CONCLUSIONS: Although detailed background information was not collected on individual cases, the prevalence found is indicative of systematic industry-wide, over-prescription of psychotropic medications as a first-line treatment for BPSD. This study highlights a clear need for further research and interventions in this area.

Socioeconomic status and treatment of depression during pregnancy: a retrospective population-based cohort study in British Columbia, Canada.

Women at the lower end of the socioeconomic distribution have higher rates of depression in pregnancy; however, we know little about the role of socioeconomic status (SES) in determining their treatment. Herein, we investigate the relationships between income and the use of health services for depression in pregnancy. This retrospective cohort study using population-based administrative datasets included all women who delivered a live infant in the province of British Columbia, Canada (population of 4.3 million) between April 1st, 2000 and December 31st, 2009. We restricted to women with an indication of depression during pregnancy and examined their use of health services to treat depression by income quintile. Women in the highest income quintile were significantly more likely to see a psychiatrist for depression during pregnancy and to fill prescriptions for serotonin reuptake inhibitor (SRI) antidepressants than women in the lowest income quintile. Women at the lower end of the income distribution were more likely to have a GP visit for depression. Women at the low end of the income distribution were more likely to end up in hospital for depression or a mental health condition during pregnancy and more likely to receive a benzodiazepine and/or an antipsychotic medication. Our findings suggest a critical gap in access to health services for women of lower income suffering from depression during pregnancy, a time when proper access to effective treatment has the most potential to improve the long-term health of the developing child and the whole family unit.

A new nomenclature for classifying psychotropic drugs.

The Neuroscience-based Nomenclature (NbN) for psychotropic drugs was developed as an alternative to the current Anatomical Therapeutic Chemical (ATC) indication-based classification in order to provide more precise designations for this drug class. The ATC nomenclature for psychotherapeutics is limited in that it fails to specify either pharmacological domains or mechanism of action and also does not describe all the potential uses of a particular agent. The disconnect between the drug classification and its clinical use is not very useful for scientific purposes and is confusing for patients and caregivers, often leading to a misunderstanding of the intended effects of the prescribed medication and, most importantly, to low treatment adherence. The NbN classifies psychopharmacological agents on the basis of contemporary scientific information on their pharmacology and mechanisms of action so as to provide physicians clear alternatives when selecting or altering therapeutic regimens. The classification of each psychotropic drug includes four additional dimensions: approved indications; efficacy and side effects; practical note; neurobiology. By emphasizing the pharmacology and the molecular mechanism of action, NbN provides a vehicle for clinicians and basic scientists to improve the understanding and clinical use of this important drug class.

Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review.

OBJECTIVE: The objective of this review was to examine prevalence and patterns of psychopharmacotherapy in individuals with autism spectrum disorder (ASD). METHOD: A systematic literature search in PubMed, CINAHL, and PsycINFO was performed, including articles published up to November 18, 2015. RESULTS: A total of 47 studies (data collection: 1976-2012), encompassing >300 000 individuals with ASD, were included. The prevalence of psychopharmacotherapy ranged from 2.7% to 80% (median (overall): 45.7%; median (children): 41.9%; median (adults): 61.5%), with psychotropic polypharmacy occurring in 5.4-54% (median: 23.0%). Regarding drug classes, antipsychotics were most frequently used, followed by attention-deficit/hyperactivity disorder (ADHD) medication and antidepressants. Both older age and psychiatric comorbidity were associated with higher prevalences of psychopharmacotherapy and psychotropic polypharmacy. There were no time trends in psychopharmacotherapy prevalence observable. CONCLUSION: Despite a lack of pharmacological treatment options for ASD core symptoms, the prevalence of psychopharmacotherapy and polypharmacy in ASD patients is considerable, which is probably due to the treatment of non-core ASD symptoms and psychiatric comorbidities. While there is some evidence for the use of antipsychotics and ADHD medication for these indications, the use of antidepressants should be limited to selected cases.

New Psychoactive Substances (NPS) - a Challenge for the Addiction Treatment Services.

Over the last few years, hundreds of new psychoactive substances (NPS) have been identified in Europe. Apart from some herbal compounds, NPS mainly include synthetic cannabinoids and a range of new synthetic stimulants (e. g., cathinones). Synthetic NPS are often developed whilst modifying the basic chemical (e. g., phenethylamine or tryptamine) structure. Although the pharmacology and toxicology of most NPS are hardly known, they are being offered, especially online, as "bath salts," as "incense mixtures," or under other misleading labels. In addition, NPS are advertised as "legal highs," suggesting that, in contrast to substances regulated by the national laws, trading with NPS is legal. Although only little is known about the prevalence of NPS use, some of these molecules may be associated with a range of severe adverse reactions. Indeed, different from cannabis, synthetic cannabinoid users may present with epileptic seizures, loss of consciousness, and a range of persisting psychopathological disorders. Future studies should inform better-tailored management strategies.

Management of mood and anxiety disorders in patients receiving opioid agonist therapy: Review and meta-analysis.

BACKGROUND AND OBJECTIVES: Patients with opioid use disorders and mood and anxiety symptoms have a variable prognosis. Few randomized controlled trials (RCTs) have evaluated treatment of depression or anxiety in patients receiving opioid agonist therapies (OAT). This review evaluates studies of pharmacotherapy/psychotherapy for treating symptoms of depression or anxiety in patients receiving OAT. METHODS: Public databases were searched for clinical trials of pharmacotherapy or psychotherapy for managing depression or anxiety symptoms in adults receiving OAT. Subsequently, we conducted a random effects meta-analysis model of RCTs by antidepressants subclasses. RESULTS: In our literature search, we identified 22 RCTs, eight of which were eligible for meta-analysis. Seven studies evaluated antidepressants in patients already maintained on OAT; two studies reported significant results for antidepressant effects versus placebo. Similarly, two of the seven studies that initiated antidepressants with OAT had advantages over placebo. Meta-analysis of grouped data revealed that tricyclic antidepressants (TCAs) (n = 235) significantly improved mean depression scores (SMD = -2.35, 95%CI: [-4.35, -0.34], z = -2.29, p = .022) while Selective Serotonin Reuptake Inhibitors (SSRIs) (n = 311) were not significantly different than placebo (SMD = 0.47, 95%CI: [-0.35, 1.30], z = 1.12, p = .263). Four out of five studies that implemented psychotherapeutic approaches reported a greater reduction of depressive symptoms than the comparison group. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: To date, psychotherapy has the most documented evidence for efficacy. TCAs appears effective but with more adverse effects than SSRIs. Further studies of OAT and adjunct antidepressant treatments for dual diagnosis patients are warranted. (Am J Addict 2017;26:551-563).

Psychoactive substances belonging to the amphetamine class potently activate brain carbonic anhydrase isoforms VA, VB, VII, and XII.

Identifying possible new biological activities of psychoactive substances belonging to various chemical classes may lead to a better understanding of their mode of action and side effects. We report here that amines structurally related to amphetamine, a widely used psychoactive substance, such as amphetamine, methamphetamine, phentermine, mephentermine, and chlorphenteramine, potently activate several carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in important physiological functions. Of the 11 investigated human (h) isoforms, the widespread hCA I and II, the secreted hCA VI, as well as the cytosolic hCA XIII, and membrane-bound hCA IX and XIV were poorly activated by these amines, whereas the extracellular hCA IV, the mitochondrial enzymes hCA VA/VB, the cytosolic hCA VII, and the transmembrane isoform hCA XII were potently activated. Some of these enzymes are abundant in the brain, raising the possibility that some of the cognitive effects of such psychoactive substances might be related to their activation of these enzymes.

Categorization of psychoactive substances into "hard drugs" and "soft drugs": a critical review of terminology used in current scientific literature.

BACKGROUND: Precise terminology and definitions are important components of scientific language. Although the terms "hard drugs" and "soft drugs" are used widely by professionals, neither the International Classification of Diseases nor the Diagnostic and Statistical Manual classify psychoactive substances into the categories "hard" and "soft." OBJECTIVES: To analyze the occurrence of the terms "hard drugs" and "soft drugs" in recent scientific literature and to establish the degree of consensus in labeling psychoactive substances as "hard" or "soft." METHODS: A critical review of scientific papers listed in PubMed and Scopus between 2011 and 2015. Three hundred thirty-four articles were initially identified as potentially relevant for review, 132 of which were included in the final analysis. RESULTS: One hundred twenty-four articles used the term "hard drugs" and 84.7% provided examples of substances considered "hard." Forty-four articles used the term "soft drugs" and 90.9% provided examples of substances considered "soft." Citations of relevant articles supporting categorization as "hard" or "soft" were not given in 90% of the articles. The authors often provided no or only very sparse information on their reasons for considering specific drugs as "hard" or "soft." CONCLUSIONS: Although it initially appeared that there is substantial agreement as to which psychoactive substances should be regarded as "hard" and "soft," closer inspection shows that the dividing line is blurred without clear criteria for categorization. At this time, it remains uncertain whether these terms should persist in the scientific literature. We therefore recommend these terms should be avoided or, if used, be clearly and precisely defined.

Schedules of Controlled Substances: Placement of 10 Synthetic Cathinones Into Schedule I. Final rule.

With the issuance of this final rule, the Drug Enforcement Administration places 10 synthetic cathinones: 4-methyl-N-ethylcathinone (4-MEC); 4-methyl-alpha-pyrrolidinopropiophenone (4-MePPP); alpha-pyrrolidinopentiophenone ([alpha]-PVP); 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone, bk-MBDB e); 2-(methylamino)-1-phenylpentan-1-one (pentedrone); 1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone, bk-MBDP); 4-fluoro-N-methylcathinone (4-FMC, flephedrone); 3-fluoro-N-methylcathinone (3-FMC); 1-(naphthalen-2-yl)-2-(pyrrolidin-1-yl)pentan-1-one (naphyrone); alpha-pyrrolidinobutiophenone ([alpha]-PBP) and their optical, positional, and geometric isomers, salts and salts of isomers, whenever the existence of such salts, isomers, and salts of isomers is possible, into schedule I of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after opportunity for a hearing through formal rulemaking. This rule continues the imposition of the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle 4-MEC, 4-MePPP, [alpha]-PVP, butylone, pentedrone, pentylone, 4-FMC, 3- FMC, naphyrone, or [alpha]-PBP.

[Guidelines for the prescription of mood stabilizers for adolescents: A literature review]. / Bonnes pratiques pour la prescription de thymorégulateurs à l'adolescence : une revue de la littérature.

INTRODUCTION: Adolescence is a unique phase of the human developmental process. In adolescents, psychotropic medications may have different efficacy and tolerance profiles compared to those at other stages of the lifespan. Mood stabilizers are a complex pharmacological category including lithium, some anticonvulsants, and some second generation antipsychotics. Focusing on this class of pharmacological agents, we aim to answer the following questions: in which indications and according to which modalities should mood stabilizers be prescribed during adolescence? METHODS: Information was sought from the websites of the French Haute Autorité de santé (HAS) and Agence nationale de sécurité du médicament et des produits de santé (ANSM), the American Food and Drug Administration (FDA) and the British National Institute for Health and Clinical Excellence (NICE). Guidelines from the American Academy of Child and Adolescent Psychiatry (AACAP) were also reviewed. Additional articles were found using PubMed and Google Scholar. We assumed that guidelines published by a national institute were the most relevant, second information from medical academies, then literature reviews, and finally single studies. Practical prescription data were also sought from the French Vidal Drug Dictionary. RESULTS: For bipolar disorder in adolescents, lithium has been the first drug licensed in France (from the age of 16) and in the USA (from the age of 12), with indications for acute mania and preventive treatment. Benefits for impulsive and self-aggressive behaviour disorders (especially relevant in case of borderline personality disorder) have also been documented, although lithium has not been licensed in any country for those indications. Extended-release tablets are usually used, at doses targeting for a lithiemia between 0.8 and 1.2mEq/L 12hours after last intake. Because of a narrow therapeutic window and potential side effects (especially nephrotoxicity), lithium prescription requires regular blood tests and good treatment compliance. None of the anticonvulsants has been licensed by a national drug administration as a mood stabilizer in adolescents. However, the AACAP recommends valproate as a first line treatment for mania, even though the NICE and the ANSM caution that valproate should not be used by women of child bearing age. Besides its teratogenic and endocrine side effects, valproate exposes one to the risk of hepatic toxicity. That is why regular liver function tests should be prescribed when valproate is chosen. According to the AACAP, carbamazepine (which is licensed for the treatment of mania in adults) is not a first line treatment for adolescents. Indeed, no clinical study has demonstrated its efficacy on manic episodes in adolescents. Moreover, carbamazepine exposes one to the risk of agranulocytosis. Lamotrigine has not been approved for adolescents, but some studies suggest its efficacy for bipolar depression (often a treatment-resistant phase) in this age group. Major side effects are the risk of Lyell or Stevens-Johnsons syndrome (which usually occur within the first eight weeks of treatment). There is no need for biological tests, just clinical monitoring. Pharmacological interactions between lamotrigine and oral contraceptives require caution. Finally, the use of some second generation antipsychotics for bipolar disorder in adolescents has been approved by national drug administrations. In France, only aripiprazole is licensed for acute mania (from the age of 13). In the USA, aripiprazole is licensed from the age of 10 for acute mania and preventive treatment, while risperidone and quetiapine are licensed from the age of 10 for acute mania, and olanzapine is licensed from the age of 13 for acute mania. The AACAP recommends second generation antipsychotics as a first line treatment for bipolar disorder. Moreover, the AACAP and the NICE recommend second generation antipsychotics for behavioural disorders in adolescents. Recommended doses are usually lower and titration slower than for adults. As in adults, adverse effects are metabolic, motor and cognitive disorders. Moreover, hyperprolactinemia, sedation and weight gain are more frequent than in adults. DISCUSSION: Epidemiologic data for prescription of mood stabilizers in adolescents only partially concord with recommendations from drug administrations and scientific societies. On the one hand, there is a trend toward preferential prescription of second generation antipsychotics, on the other hand lithium is hardly prescribed to adolescents, less often than anticonvulsants. Thus, without approval from any drug administration, the anticonvulsants are often preferred to lithium (because of lithium's potential risks due to noncompliance or voluntary poisoning) and to second generation antipsychotics (because of their tolerance profile). Nevertheless, for prescribers it is a complex matter to compare side effects: the frequency and intensity of adverse effects is quite variable from one mood stabilizer to another, and such a thing as an expected value is therefore hard to define. Regardless of the medication chosen, compliance and therapeutic alliance are major issues. Compliance is especially low during adolescence (less than 40% according to a study on bipolar disorder). This lack of compliance has multiple determinants: poor acceptance or misunderstanding of the psychiatric disorder, indirect effects of bad relationships with parents and more generally adults, but also reckless behaviour or death wishes. Improving therapeutic alliance appears as a major challenge for health practitioners dealing with youth. One interesting path of research could be the therapeutic education programs using humanistic communication techniques (addressing both adolescents and their parents) which have already produced encouraging results.

Suicidal Behavior in Mood Disorders: Response to Pharmacological Treatment.

Suicidal behavior is strongly associated with depression, especially if accompanied by behavioral activation, dysphoria, or agitation. It may respond to some treatments, but the design of scientifically sound, ethical trials to test for therapeutic effects on suicidal behavior is highly challenging. In bipolar disorder, and possibly also unipolar major depression, an underprescribed medical intervention with substantial evidence of preventive effects on suicidal behavior is long-term treatment with lithium. It is unclear whether this effect is specifically antisuicidal or reflects beneficial effects of lithium on depression, mood instability, and perhaps aggression and impulsivity. Antisuicidal effects of anticonvulsant mood stabilizers (carbamazepine, lamotrigine, valproate) appear to be less than with lithium. Further evaluation is needed for potential antisuicidal effects of atypical antipsychotics with growing evidence of efficacy in depression, particularly acute bipolar depression, while generally lacking risk of inducing agitation, mania, or mood instability. Short-term and long-term value and safety of antidepressants are relatively secure for unipolar depression but uncertain and poorly tested for bipolar depression; their effects on suicidal risk in unipolar depression may be age-dependent. Sedative anxiolytics are virtually unstudied as regards suicidal risks. Adequate management of suicidal risks in mood disorder patients requires comprehensive, clinically skillful monitoring and timely interventions.

Only 10% of the psychotropic drug use for neuropsychiatric symptoms in patients with dementia is fully appropriate. The PROPER I-study.

BACKGROUND: This study explores the appropriateness of psychotropic drug (PD) use for neuropsychiatric symptoms (NPS) in nursing home patients with dementia. METHODS: A cross-sectional study on 559 patients with dementia residing on dementia special care units in Dutch nursing homes was conducted. Appropriateness of PD use was assessed using the Appropriate Psychotropic drug use In Dementia (APID) index. The APID index score is calculated using information about individual PDs from patients' medical records. The index encompasses seven (different) domains of appropriateness, i.e. indication, evaluation, dosage, drug-drug interactions, drug-disease interactions, duplications, and therapy duration. RESULTS: A total of 578 PDs were used for NPS by 60% of the nursing home patients. Indication, evaluation, and therapy duration contributed the most to inappropriate use. Ten per cent of the PDs scored fully appropriate according to the APID index sum score, 36% scored fully appropriate for indication, 46% scored fully appropriate for evaluation, and 58% scored fully appropriate for therapy duration. Antidepressants were used the most appropriately, and antiepileptics the most inappropriately. CONCLUSIONS: The minority of the PD use was fully appropriate. The results imply that PD use for NPS in dementia can be improved; the appropriateness should be optimized with a clinical focus on the appropriate indications, evaluations, and therapy duration.

Multi-psychotropic drug prescription and the association to neuropsychiatric symptoms in three Norwegian nursing home cohorts between 2004 and 2011.

BACKGROUND: Neuropsychiatric symptoms, such as affective symptoms, psychosis, agitation, and apathy are common among nursing home patients with and without dementia. Treatment with one or more psychotropic drug is often without explicit clinical indication, despite low treatment efficacy, and potential side effects. We aim to investigate the multi-psychotropic drug use to identify factors and patient characteristics associated with multi-use. METHODS: We analysed three cohorts from 129 Norwegian nursing homes, collected between 2004 and 2011. Patients (N = 4739) were assessed with the Neuropsychiatric Inventory - Nursing Home version (NPI-NH), Clinical Dementia Rating scale, and Physical Self Maintenance Scale. We used ordinal logistic regression to analyse associations between psychotropics (antidepressants, antipsychotics, anxiolytics, hypnotics, and anti-dementia drugs), patient characteristics, and neuropsychiatric symptoms. RESULTS: Patients used on average 6.6 drugs; 27 % used no psychotropics, 32 % one, and 41 % multiple psychotropic drugs (24 % two, 17 % ≥3). Thirty-nine percent were prescribed antidepressants, 30 % sedatives, 24 % anxiolytics, and 20 % antipsychotics. The total NPI-NH score was associated with multi-use (OR 1.02, 95 % CI 1.02-1.03), and increased from a mean of 13.5 (SD 16.3) for patients using none, to 25.5 (21.8) for patients using ≥3 psychotropics. Affective symptoms (depression and anxiety) were most strongly associated with multi-psychotropic drug use (OR 1.10, 95 % CI: 1.09-1.12). Female gender, independency in daily living, younger age, dementia, and many regular drugs were also associated with multi-use. CONCLUSION: Forty-one percent were exposed to multi-psychotropic drug prescriptions. Contrary to current evidence and guidelines, there is an extensive use of multiple psychotropic drugs in patients with severe NPS and dementia.

Schedules of Controlled Substances: Extension of Temporary Placement of 10 Synthetic Cathinones in Schedule I of the Controlled Substances Act. Final order.

The Administrator of the Drug Enforcement Administration is issuing this final order to extend the temporary schedule I status of 10 synthetic cathinones pursuant to the temporary scheduling provisions of the Controlled Substances Act. The 10 substances are: 4-methyl-N-ethylcathinone (4-MEC); 4-methyl-alpha-pyrrolidinopropiophenone (4-MePPP); alpha-pyrrolidinopentiophenone ([alpha]-PVP); 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone); 2-(methylamino)-1-phenylpentan-1-one (pentedrone); 1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone); 4-fluoro-N-methylcathinone (4-FMC); 3-fluoro-N-methylcathinone (3-FMC); 1-(naphthalen-2-yl)-2-(pyrrolidin-1-yl)pentan-1-one (naphyrone); and alpha-pyrrolidinobutiophenone ([alpha]-PBP) [hereinafter 4-MEC, 4-MePPP, [alpha]-PVP, butylone, pentedrone, pentylone, 4-FMC, 3-FMC, naphyrone, and [alpha]-PBP, respectively], including their optical, positional, and geometric isomers, salts, and salts of isomers. The current final order temporarily placing 4-MEC, 4-MePPP, [alpha]-PVP, butylone, pentedrone, pentylone, 4-FMC, 3-FMC, naphyrone, and [alpha]-PBP into schedule I is in effect through March 6, 2016. This final order will extend the temporary scheduling of 4-MEC, 4-MePPP, [alpha]-PVP, butylone, pentedrone, pentylone, 4-FMC, 3-FMC, naphyrone, and [alpha]-PBP for one year, or until the permanent scheduling action for these 10 substances is completed, whichever occurs first.