Prescription Psychotherapeutic Drug Use and Nicotine Use among Young People in the United States.

Background: While prescription psychotherapeutic drug use (PPDU) and nicotine use pose substantial problems in isolation, they pose an increased risk in combination. This study aimed to estimate the prevalence of PPDU for young people, stratified by nicotine use status. A trend analysis was used to examine changes in PPDU and nicotine use over time. Methods: We used a cross-sectional population-based sample of young people aged 16-25 years (n = 10,454) from the National Health and Nutrition Examination Survey (NHANES, 2003-2018). For each data cycle, the prevalence of self-reported PPDU and nicotine including pain relievers, sedatives, stimulants, and tranquilizers was estimated. Using Joinpoint regression, we tested for significant changes in trends using a log-linear model and permutation test approach and produced the average data cycle percentage change (ADCPC). Results: From 2003 to 2018, 6.7% of young people had PPDU and 27.3% used nicotine. The prevalence of cigarette smoking decreased while other nicotine product use increased (p's < 0.001). Those who used nicotine were more likely to have PPDU (8.2%; 95% CI = 6.5%, 9.8%) vs. non-nicotine use (6.1%; 95% CI = 5.1%, 7.0%; p = 0.01). Results indicated a decreasing trend for nicotine use (ADCPC = -3.8, 95% CI = -7.2, -0.3; p = 0.04), but not for PPDU (ADCPC = 1.3; 95% CI = -4.7, 7.8; p = 0.61). On further examination, opioid use decreased, sedative use remained stable, and stimulant and tranquilizer use increased over time. Conclusions: From 2003 to 2018, young people who used nicotine had a higher prevalence of PPDU than those who did not. Clinicians should communicate the association between nicotine use and prescription drugs when prescribing or managing young patients' medications.

Pharmacotherapy of 1,044 inpatients with posttraumatic stress disorder: current status and trends in German-speaking countries.

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder with limited approved pharmacological treatment options and high symptom burden. Therefore, real-life prescription patterns may differ from guideline recommendations, especially in psychiatric inpatient settings. The European Drug Safety Program in Psychiatry ("Arzneimittelsicherheit in der Psychiatrie", AMSP) collects inpatients' prescription rates cross-sectionally twice a year in German-speaking psychiatric hospitals. For this study, the AMSP database was screened for psychiatric inpatients with a primary diagnosis of PTSD between 2001 and 2017. N = 1,044 patients with a primary diagnosis of PTSD were identified with 89.9% taking psychotropics. The average prescription rate was 2.4 (standard deviation: 1.5) psychotropics per patient with high rates of antidepressant drugs (72.0%), antipsychotics drugs (58.4%) and tranquilizing drugs (29.3%). The presence of psychiatric comorbidities was associated with higher rates of psychotropic drug use. The most often prescribed substances were quetiapine (24.1% of all patients), lorazepam (18.1%) and mirtazapine (15.0%). The use of drugs approved for PTSD was low (sertraline 11.1%; paroxetine 3.7%). Prescription rates of second-generation antipsychotic drugs increased, while the use of tranquilizing drugs declined over the years. High prescription rates and extensive use of sedative medication suggest a symptom-driven prescription (e.g., hyperarousal, insomnia) that can only be explained to a minor extent by existing comorbidities. The observed discrepancy with existing guidelines underlines the need for effective pharmacological and psychological treatment options in psychiatric inpatient settings.

Chemical restraint: A qualitative synthesis review of adult service user and staff experiences in mental health settings.

With an imperative to reduce or eliminate the use of coercive practices in mental health care it is important to understand the experience of service users and staff. This review aimed to synthesize qualitative studies, published between 1996 and 2020, reporting on mental health service users' and staff's experiences of chemical restraint. The databases PsycINFO, CINAHL, MEDLINE, Embase, Emcare, Web of Science, and Scopus were searched. Three analytic themes were identified from 17 included articles, synthesizing the experiences of service users and staff. These were "Unjustified versusjustified," "Violence versus necessity," and "Reflecting back: Positives and negatives." Service users viewed chemical restraint as an unjustified response to "behaviors of concern" and experienced it as a violent act with negative outcomes, although some saw it as necessary in retrospect and preferred it to other forms of coercion. Staff generally viewed it as a justified response to "behaviors of concern" and experienced it as appropriate within the constraints of staff numbers and limited alternatives. These findings identify nuances not apparent in the literature, which has generally conflated all forms of coercive practices.

Pharmacotherapy of psychiatric inpatients with adjustment disorder: current status and changes between 2000 and 2016.

Adjustment disorder is a temporary change in behaviour or emotion as a reaction to a stress factor. Therapy consists of psychotherapy, and pharmacotherapy can be advised. However, data on the real-life pharmacological treatment are sparse. Prescription data for 4.235 psychiatric inpatients diagnosed with adjustment disorder in the time period 2000-2016 were analysed. The data were obtained from the Drug Safety Programme in Psychiatry (AMSP). Data were collected on two reference days per year; prescription patterns and changes over time were analysed. Of all patients, 81.2% received some type of psychotropic drug. Mostly antidepressants (59.8%), antipsychotics (35.5%), and tranquilisers (22.6%) were prescribed. Prescription rates for antidepressants decreased slightly over the years, while rates for antipsychotics increased, especially for atypical antipsychotics. It is important to note that the diagnosis "adjustment disorder" is most likely a working diagnosis that is used for patients in immediate need of psychiatric aid. Overall, pharmacotherapy for inpatients with this diagnosis is mostly symptom-oriented and focuses on depressive moods, agitation and anxiety. Therapy regimes changed over time and show an increased use of atypical antipsychotics with sedative properties. However, for most of the medication, there are neither evidence-based studies nor guidelines, and drugs might be contraindicated in some cases.

General practitioners' management of patients with psychological stress: audit results from Denmark.

BACKGROUND: In western countries, psychological stress is among the most common causes of long-lasting sick leave and a frequent reason to consult the general practitioner (GP). This study aimed to investigate how GPs manage patients with psychological stress and how the management is associated with the patient's sex, the GP's assessment of causality, and coexisting mental disorders. METHODS: We conducted an audit of consecutive cases in Danish general practice. The GPs used electronic medical records to fill in a registration form for each 18-65-year-old patient with whom they had had at least one consultation regarding stress during the past 6 months. Only patients initially in the workforce were included. Age- and sex-adjusted binary regression was applied. RESULTS: Fifty-six GPs (61% women) identified 785 cases. The patients' mean age was 44 years and 70% were women. The cause of stress was considered at least partially work-related in 69% of the cases and multifactorial in a third of cases. The management included sick leave (54%), counselling (47%), pharmaceutical treatment (37%), and referral to psychologist (38%). Compared to women, stress in men was less often considered work-related (RR: 0.84, CI95%: 0.77-0.92) and men were less often sick-listed (RR: 0.83 CI95%: 0.73-0.96) but were more often prescribed tranquilizers (RR: 1.72 CI95%: 1.08-2.74). CONCLUSIONS: GPs' management of patients with stress usually involve elements of counselling, sick leave, referral to psychologist, and medication. Women and men with stress are perceived of and managed differently.

ORAL HALOPERIDOL PREMEDICATION TO REDUCE CAPTURE STRESS PRIOR TO XYLAZINE-KETAMINE ANESTHESIA IN CAPTIVE SPOTTED DEER (AXIS AXIS).

A prospective clinical trial was performed to evaluate the efficacy of haloperidol premedication prior to xylazine-ketamine anesthesia with a goal of reducing capture stress in adult male captive spotted deer (Axis axis). On the morning of the study, deer were fed a banana either containing haloperidol tablets (1 mg/kg) (haloperidol group, n = 10) or without haloperidol (placebo group, n = 10). Six hours postadministration, xylazine (3 mg/kg) and ketamine (2 mg/kg) was administered intramuscularly via a dart. Rectal temperature, heart rate, respiratory rate, and SpO2 (percent hemoglobin saturation) were recorded at 5-min intervals. Blood gas analysis was performed at time 0 (venous blood) and 10 and 20 min (arterial blood) postinduction. Serum cortisol was determined from venous blood (35 min postinduction), following which yohimbine was administered at a dose of 0.15 mg/kg intramuscular and 0.15 mg/kg intravenous. Statistical analysis of repeated measures data was performed with a two-way analysis of variance. Paired data were analyzed with a Wilcoxon rank-sum test (categorical data) or a paired t-test (continuous data). Significance was set at P ≤ 0.05, and results were expressed as mean ± SEM. There was no significant difference in induction time or recovery time between treatment groups. Rectal temperature and heart rate were significantly lower in the haloperidol group. Both groups demonstrated acidosis with venous pH being significantly lower in the placebo group when compared to the haloperidol group. Serum cortisol and arterial plasma lactate were lower in the haloperidol group indicative of reduced stress and physical exertion. Haloperidol premedication proved to be beneficial in reducing capture stress, when administered prior to xylazine-ketamine anesthesia, in spotted deer.

[Rapid tranquilisation in adults†: algorithm proposed for psychopharmacological treatment]. / Agitation aiguë chez l'adulte†: proposition d'un algorithme de traitement psychopharmacologique.

Acute treatment of agitation in psychiatry is one of the urgent situations for which management recommendations are needed. Various existing international recommendations have been evaluated and adapted to our clinical practice and to the drugs available in Switzerland in order to propose a uniform management strategy in our hospital. This strategy includes a treatment choice algorithm with different options depending on the clinical situation and the possible route of administration. Dose recommendations for the oral and intramuscular routes, certain pharmacokinetic parameters, as well as risks of interactions and important warnings are also included in this clinical recommendation.

Le traitement aigu de l'agitation en psychiatrie fait partie des situations urgentes pour lesquelles des recommandations de prise en charge sont nécessaires. Diverses recommandations internationales existantes ont été évaluées et adaptées à notre pratique clinique ainsi qu'aux médicaments disponibles en Suisse afin de proposer une stratégie de prise en charge uniformisée au sein de notre hôpital. Cette stratégie inclut un algorithme de choix de traitement avec différentes options selon la situation clinique et la voie d'administration possible. Des recommandations de doses pour les voies orale et intramusculaire, certains paramètres pharmacocinétiques, ainsi que les risques d'interactions et des mises en garde importantes figurent également dans cette recommandation clinique.

Agreement between self-reported and registry-based use of sleep medications and tranquilizers.

PURPOSE: The purpose of the present study was to assess the agreement between self-reported use of sleep medications and tranquilizers and dispensed hypnotics and anxiolytics. METHODS: Self-reported medication use was obtained from the population-based survey Health and Environment in Oslo (HELMILO) (2009-2010) (n = 13 019). Data on dispensed hypnotics and anxiolytics were obtained from the Norwegian Prescription Database (NorPD). As measures of validity, we calculated sensitivity and specificity using both self-reports and prescription records as the reference standard. Furthermore, we calculated Cohen's kappa. Current self-reported medication use was compared with prescription data in time windows of both 100 and 200 days preceding questionnaire completion. RESULTS: The highest sensitivity was observed for current sleep medication use in the 100-day time window (sensitivity = 0.76, 95% confidence interval [CI]: 0.74, 0.79) when using prescription records as the reference standard. Sensitivity was generally lower for tranquilizers compared with sleep medications. Cohen's kappa showed the highest agreement for the 200-day time window with substantial agreement for sleep medications (kappa = 0.64; 95% CI: 0.62, 0.67) and moderate agreement for tranquilizers (kappa = 0.45; 95% CI: 0.41, 0.48). CONCLUSIONS: The present study suggests moderate to substantial agreement between self-reported use of sleep medications and tranquilizers and dispensed drugs in a general adult population. The magnitude of agreement varied according to drug category and time window. Since self-reported and registry-based use of these drug classes does not match each other accurately, limitations of each data source should be considered when such medications are applied as the exposure or outcome in epidemiologic studies.

Prescribing practices of Indian psychiatrists in the treatment of bipolar disorder.

OBJECTIVE: The treatment of bipolar disorder is challenging because of its clinical complexity and availability of multiple treatment options, none of which are ideal mood stabilizers. This survey studies prescription practices of psychiatrists in India and their adherence to guidelines. METHOD: In total, 500 psychiatrists randomly selected from the Indian Psychiatric Society membership directory were administered a face-to-face 22-item questionnaire pertaining to the management of bipolar disorder. RESULTS: For acute mania, most practitioners preferred a combination of a mood stabilizer and an atypical antipsychotic to monotherapy. For acute depression, there was a preference for a combination of an antidepressant and a mood stabilizer over other alternatives. Electroconvulsive therapy was preferred in the treatment of severe episodes and to hasten the process of recovery. Approximately, 50% of psychiatrists prescribe maintenance treatment after the first bipolar episode, but maintenance therapy was rarely offered lifelong. While the majority (85%) of psychiatrists acknowledged referring to various clinical guidelines, their ultimate choice of treatment was also significantly determined by personal experience and reference to textbooks. LIMITATIONS: The study did not study actual prescriptions. Hence, the responses to queries in the survey are indirect measures from which we have tried to understand the actual practices, and of course, these are susceptible to self-report and social-desirability biases. This was a cross-sectional study; therefore, temporal changes in responses could not be considered. CONCLUSION: Overall, Indian psychiatrists seemed to broadly adhere to recommendations of clinical practice guidelines, but with some notable exceptions. The preference for antidepressants in treating depression is contrary to general restraint recommended by most guidelines. Therefore, the efficacy of antidepressants in treating bipolar depression in the context of Indian psychiatrists' practice needs to be studied systematically. Not initiating maintenance treatment early in the course of illness may have serious implications on the long-term outcome of bipolar disorder.

Prolactin, flupenthixol decanoate and first episode schizophrenia - clinical and laboratory correlates.

First-episode psychosis (FEP) patients are more sensitive to neuroleptic side-effects such as hyperprolactinemia. We examined the prolactin levels of previously minimally treated patients with first episode schizophrenia over their first year of treatment with flupenthixol decanoate and the relationship between prolactin levels, gender and clinical features of schizophrenia. Prolactin levels were assessed at three monthly intervals in 126 patients with first-episode schizophrenia in a single-site study conducted over 12 months during treatment with flupenthixol decanoate according to a fixed protocol. The mean prolactin level for the total sample was 11.91 ng/ml (standard deviation [SD]15.52) at baseline. Women had higher levels of prolactin than men at month 3, 6 and 12, reaching statistical significance at month 12 (p = 0.02). At 12 months more women than men had hyperprolactinemia (defined as more than 20 ng/ml for males, and as more than 25 ng/ml for females (p = 0.007). Using a mixed effect model, there was a significant association between prolactin change scores over 12 months and gender (p = 0.025) as well as Positive and Negative Syndrome Scale (PANSS) total scores (p = 0.001). In addition female gender (p = 0.04) and age (p = 0.02) correlated with the risk of hyperprolactinemia as categorical variable. In this study treatment with flupenthixol decanoate was associated with relatively low levels of hyperprolactinemia, likely owing to flupenthixol's relatively atypical mode of action, as well as to the low doses used in our study. We found an inverse correlation between total PANSS scores and prolactin levels, which could support the suggested theory of prolactin having antipsychotic properties. Our study confirms the importance of gender on the prolactin raising effects of antipsychotic treatment.

The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium.

BACKGROUND: The Richmond Agitation-Sedation Scale (RASS) is commonly used to assess psychomotor activity; however, to the authors' knowledge, its minimal clinically important difference (MCID) has not been determined to date. The objective of the current study was to identify the MCID for RASS using 2 anchor-based approaches. METHODS: The current study was a secondary analysis of a randomized controlled trial to compare the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium. The primary outcome was change in RASS (10-point numeric rating scale ranging from -5 [unarousable] to +4 [combative]) from baseline to 8 hours after treatment administration. The sensitivity-specificity and within-patient change methods were used to identify the MCID, with the anchor being patient comfort after the study intervention as perceived by caregivers and nurses. RESULTS: A total of 90 patients were randomized and 58 (64%) received the study medication for restlessness/agitation (mean baseline RASS, 1.6). A total of 23 caregivers (61%) and 23 nurses (55%) perceived that the patient was more comfortable after treatment. Using the sensitivity-specificity method, the optimal RASS reduction was ≥4 points according to both caregivers (sensitivity of 61% and specificity of 80%; area under the curve, 0.71) and nurses (sensitivity of 73% and specificity of 84%; area under the curve, 0.78). The RASS cutoff value based on the within-patient change method was similar (-4.2 for caregivers and -4.0 for nurses). CONCLUSIONS: For patients with persistent restlessness/agitation, a reduction of ≥4 points in RASS was considered to be the MCID for both nurses and caregivers. These preliminary findings may have implications for sample size calculation and the interpretation of treatment effect in future delirium trials. Cancer 2018;124:2246-52. © 2018 American Cancer Society.

Trends of Polypharmacy and Prescription Patterns of Antidepressants in Asia.

PURPOSE: Little is known regarding the trend of polypharmacy in Asia. We used data from 5 Asian countries to examine the patterns of antidepressant (AD) prescription and trends of psychotropic polypharmacy over time. METHODS: We used the cross-sectional, pharmacoepidemiological data from 2004 and 2013 REAP-AD (Research on Asian Psychotropic Prescription Patterns for Antidepressants) to examine the patterns of AD prescriptions in clinical settings in China, Japan, Korea, Singapore, and Taiwan. We compared the trend in polypharmacy (ie, concomitant use of ≥2 classes of psychotropic) among individuals receiving AD prescriptions in 2004 and 2013 using multivariable logistic regression models in different diagnostic categories. RESULTS: The proportion of patients with psychotropic polypharmacy decreased from 2004 to 2013 in all 3 diagnostic categories, including mood disorders (adjusted odds ratio [aOR], 0.44 [0.35-0.56]; P < 0.001), anxiety disorders (aOR, 0.58 [0.36-0.94]; P = 0.028), and psychotic disorders (aOR, 0.18 [0.05-0.60]; P = 0.006). Among individuals with AD prescriptions, concomitant use of anxiolytics (including sedative-hypnotics) decreased in patients with mood disorders (aOR, 0.34 [0.27-0.42]; P < 0.001) and anxiety disorders (aOR, 0.43 [0.27-0.67]; P < 0.001). In contrast, concomitant use of antipsychotics in patients with mood disorders increased (aOR, 1.43 [1.15-1.77]; P = 0.001), and concomitant use of mood stabilizers in patients with psychotic disorders also increased (aOR, 3.49 [1.50-8.14]; P = 0.004). CONCLUSIONS: This is the first study examining trends in psychotropic polypharmacy in East Asia. We found a generally decreasing trend of psychotropic polypharmacy in contrast to the increasing trend reported from Western countries. These findings could offer significant implications for health system reform or policy making.

Risperidone for psychosis-induced aggression or agitation (rapid tranquillisation).

BACKGROUND: Aggressive, agitated or violent behaviour due to psychosis constitutes an emergency psychiatric treatment where fast-acting interventions are required. Risperidone is a widely accessible antipsychotic that can be used to manage psychosis-induced aggression or agitation. OBJECTIVES: To examine whether oral risperidone alone is an effective treatment for psychosis-induced aggression or agitation. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (up to April 2017); this register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rapid use of risperidone and other drugs, combinations of drugs or placebo for people exhibiting aggression or agitation (or both) thought to be due to psychosis. DATA COLLECTION AND ANALYSIS: We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR) and for continuous data we calculated mean difference (MD), all with 95% confidence intervals (CI) and used a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce a 'Summary of findings' tables. MAIN RESULTS: The review now contains data from nine trials (total n = 582) reporting on five comparisons. Due to risk of bias, small size of trials, indirectness of outcome measures and a paucity of investigated and reported 'pragmatic' outcomes, evidence was graded as very-low quality. None of the included studies provided useable data on our primary outcome 'tranquillisation or asleep' by 30 minutes, repeated need for tranquillisation or any economic outcomes. Data were available for our other main outcomes of agitation or aggression, needing restraint, and incidence of adverse effects.Risperidone versus haloperidol (up to 24 hours follow-up)For the outcome, specific behaviour - agitation, no clear difference was found between risperidone and haloperidol in terms of efficacy, measured as at least 50% reduction in the Positive and Negative Syndrome Scale - Psychotic Agitation Sub-score (PANSS-PAS) (RR 1.04, 95% CI 0.86 to 1.26; participants = 124; studies = 1; very low-quality evidence) and no effect was observed for need to use restraints (RR 2.00, 95% CI 0.43 to 9.21; participants = 28; studies = 1; very low-quality evidence). Incidence of adverse effects was similar between treatment groups (RR 0.94, 95% CI 0.54 to 1.66; participants = 124; studies = 1; very low-quality evidence).Risperidone versus olanzapineOne small trial (n = 29) reported useable data for the comparison risperidone versus olanzapine. No effect was observed for agitation measured as PANSS-PAS endpoint score at two hours (MD 2.50, 95% CI -2.46 to 7.46; very low-quality evidence); need to use restraints at four days (RR 1.43, 95% CI 0.39 to 5.28; very-low quality evidence); specific movement disorders measured as Behavioural Activity Rating Scale (BARS) endpoint score at four days (MD 0.20, 95% CI -0.43 to 0.83; very low-quality evidence).Risperidone versus quetiapineOne trial reported (n = 40) useable data for the comparison risperidone versus quetiapine. Aggression was measured using the Modified Overt Aggression Scale (MOAS) endpoint score at two weeks. A clear difference, favouring quetiapine was observed (MD 1.80, 95% CI 0.20 to 3.40; very-low quality evidence). No evidence of a difference between treatment groups could be observed for incidence of akathisia after 24 hours (RR 1.67, 95% CI 0.46 to 6.06; very low-quality evidence). Two participants allocated to risperidone and one allocated to quetiapine experienced myocardial ischaemia during the trial.Risperidone versus risperidone + oxcarbazepineOne trial (n = 68) measured agitation using the Positive and Negative Syndrome Scale - Excited Component.(PANSS-EC) endpoint score and found a clear difference, favouring the combination treatment at one week (MD 2.70, 95% CI 0.42 to 4.98; very low-quality evidence), but no effect was observed for global state using Clinical Global Impression - Improvement (CGI-I) endpoint score at one week (MD -0.20, 95% CI -0.61 to 0.21; very-low quality evidence). Incidence of extrapyramidal symptoms after 24 hours was similar between treatment groups (RR 1.59, 95% CI 0.49 to 5.14; very-low quality evidence).Risperidone versus risperidone + valproic acidTwo trials compared risperidone with a combination of risperidone plus valproic acid. No clear differences between the treatment groups were observed for aggression (MOAS endpoint score at three days: MD 1.07, 95% CI -0.20 to 2.34; participants = 54; studies = 1; very low-quality evidence) or incidence of akathisia after 24 hours: RR 0.75, 95% CI 0.28 to 2.03; participants = 122; studies = 2; very low-quality evidence). AUTHORS' CONCLUSIONS: Overall, results for the main outcomes show no real effect for risperidone. The only data available for use in this review are from nine under-sampled trials and the evidence available is of very low quality. This casts uncertainty on the role of risperidone in rapid tranquillisation for people with psychosis-induced aggression. High-quality pragmatic RCTs are feasible and are needed before clear recommendations can be drawn on the use of risperidone for psychosis-induced aggression or agitation.

A History of the Pharmacological Treatment of Bipolar Disorder.

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation).

BACKGROUND: Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only antipsychotic medication available in limited-resource areas. OBJECTIVES: To examine whether haloperidol alone is an effective treatment for psychosis-induced aggression or agitation, wherein clinicians are required to intervene to prevent harm to self and others. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving people exhibiting aggression and/or agitation thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes of interest included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We included trials meeting our selection criteria and providing useable data. DATA COLLECTION AND ANALYSIS: We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), and for cognitive outcomes we derived standardised mean difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce 'Summary of findings' tables which included our pre-specified main outcomes of interest. MAIN RESULTS: We found nine new RCTs from the 2016 update search, giving a total of 41 included studies and 24 comparisons. Few studies were undertaken in circumstances that reflect real-world practice, and, with notable exceptions, most were small and carried considerable risk of bias. Due to the large number of comparisons, we can only present a summary of main results.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n=220, RR 0.88, 95%CI 0.82 to 0.95, very low-quality evidence) and experienced dystonia (2 RCTs, n=207, RR 7.49, 95%CI 0.93 to 60.21, very low-quality evidence).Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n=473, RR 0.78, 95%CI 0.62 to 0.99, low-quality evidence). More people in the haloperidol group experienced dystonia (2 RCTs, n=477, RR 6.63, 95%CI 1.52 to 28.86, very low-quality evidence).Four trials (n=207) compared haloperidol with lorazepam with no significant differences with regard to number of participants asleep at one hour (1 RCT, n=60, RR 1.05, 95%CI 0.76 to 1.44, very low-quality of evidence) or those requiring additional injections (1 RCT, n=66, RR 1.14, 95%CI 0.91 to 1.43, very low-quality of evidence).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n=67, RR 8.25, 95%CI 0.46 to 147.45, very low-quality of evidence).Addition of promethazine was investigated in two trials (n=376). More people in the haloperidol group were not tranquil or asleep by 20 minutes (1 RCT, n=316, RR 1.60, 95%CI 1.18 to 2.16, moderate-quality evidence). Acute dystonia was too common in the haloperidol alone group for the trial to continue beyond the interim analysis (1 RCT, n=316, RR 19.48, 95%CI 1.14 to 331.92, low-quality evidence). AUTHORS' CONCLUSIONS: Additional data from new studies does not alter previous conclusions of this review. If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs are available, sole use of haloperidol for extreme emergency could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries risk of additional harm.After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real-world practice.

A Novel Brief Therapy for Patients Who Attempt Suicide: A 24-months Follow-Up Randomized Controlled Study of the Attempted Suicide Short Intervention Program (ASSIP).

BACKGROUND: Attempted suicide is the main risk factor for suicide and repeated suicide attempts. However, the evidence for follow-up treatments reducing suicidal behavior in these patients is limited. The objective of the present study was to evaluate the efficacy of the Attempted Suicide Short Intervention Program (ASSIP) in reducing suicidal behavior. ASSIP is a novel brief therapy based on a patient-centered model of suicidal behavior, with an emphasis on early therapeutic alliance. METHODS AND FINDINGS: Patients who had recently attempted suicide were randomly allocated to treatment as usual (n = 60) or treatment as usual plus ASSIP (n = 60). ASSIP participants received three therapy sessions followed by regular contact through personalized letters over 24 months. Participants considered to be at high risk of suicide were included, 63% were diagnosed with an affective disorder, and 50% had a history of prior suicide attempts. Clinical exclusion criteria were habitual self-harm, serious cognitive impairment, and psychotic disorder. Study participants completed a set of psychosocial and clinical questionnaires every 6 months over a 24-month follow-up period. The study represents a real-world clinical setting at an outpatient clinic of a university hospital of psychiatry. The primary outcome measure was repeat suicide attempts during the 24-month follow-up period. Secondary outcome measures were suicidal ideation, depression, and health-care utilization. Furthermore, effects of prior suicide attempts, depression at baseline, diagnosis, and therapeutic alliance on outcome were investigated. During the 24-month follow-up period, five repeat suicide attempts were recorded in the ASSIP group and 41 attempts in the control group. The rates of participants reattempting suicide at least once were 8.3% (n = 5) and 26.7% (n = 16). ASSIP was associated with an approximately 80% reduced risk of participants making at least one repeat suicide attempt (Wald χ21 = 13.1, 95% CI 12.4-13.7, p < 0.001). ASSIP participants spent 72% fewer days in the hospital during follow-up (ASSIP: 29 d; control group: 105 d; W = 94.5, p = 0.038). Higher scores of patient-rated therapeutic alliance in the ASSIP group were associated with a lower rate of repeat suicide attempts. Prior suicide attempts, depression, and a diagnosis of personality disorder at baseline did not significantly affect outcome. Participants with a diagnosis of borderline personality disorder (n = 20) had more previous suicide attempts and a higher number of reattempts. Key study limitations were missing data and dropout rates. Although both were generally low, they increased during follow-up. At 24 months, the group difference in dropout rate was significant: ASSIP, 7% (n = 4); control, 22% (n = 13). A further limitation is that we do not have detailed information of the co-active follow-up treatment apart from participant self-reports every 6 months on the setting and the duration of the co-active treatment. CONCLUSIONS: ASSIP, a manual-based brief therapy for patients who have recently attempted suicide, administered in addition to the usual clinical treatment, was efficacious in reducing suicidal behavior in a real-world clinical setting. ASSIP fulfills the need for an easy-to-administer low-cost intervention. Large pragmatic trials will be needed to conclusively establish the efficacy of ASSIP and replicate our findings in other clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02505373.

Health-related quality of life in patients with Burnout on sick leave: descriptive and comparative results from a clinical study.

PURPOSE: To explore the health-related quality of life (HRQoL), the cause of being ill, and the pharmacological treatment in patients on sick leave because of Burnout. The HRQoL among these patients was also compared with that of individuals who were working full time. METHODS: HRQoL was measured using the SWED-QUAL questionnaire, comprising 67 items grouped into 13 subscales, scored from 0 (worst) to 100 (best) points, and covering aspects of physical and emotional well-being, cognitive function, sleep, general health, social, and sexual functioning. The Burnout group (n = 94), mean age 43 years, were on 50% sick leave or more. The comparison group consisted of healthy persons (n = 88) of similar age and educational level who were working full time. RESULTS: The Burnout group had markedly low scores in general. The cause of illness was mainly work-related. Psychotropic medication was prescribed for 55%. Significantly lower scores were found in the Burnout group than in the comparison group in all subscales, p < 0.001. The median differences in scores ranged from 10 to 56 points. Differences rated by effect size were large, 0.85-2.01. CONCLUSIONS: Patients on sick leave because of Burnout rated their HRQoL as very low in general, their cause of being ill was mainly work-related, and psychotropic medication was prescribed for a majority. Their scores were markedly lower in all subscales in comparison with healthy individuals working full time. The study adds to our understanding of the situation of patients with Burnout. The results can be useful in clinical work and future research.

Medical use, nonmedical use of prescription medication and risk behaviour among Croatian adolescents.

BACKGROUND: At the drug scene some major shifts were observed, more and more reports highlighted the abuse of prescription medication. Despite the importance of controlled medication in treatment child and adolescent disorders, this increase may be a factor which influence misuse and nonmedical use of prescribed drugs among adolescents. SUBJECT AND METHODS: Croatian data from ESPAD survey in 2003, 2007 and 2011 were used, and variables selected from the international ESPAD questionnaire. Dependent variable was taking tranquilizers or sedatives prescribed by doctor in the past 12 months. Independent variables were nonmedical use of tranquilizers/sedatives, use of other psychoactive substances, school performance, truancy, delinquent behaviour, satisfaction with relationships with parents, friends, health, self-perception, financial situation and symptoms of depression. The respondents were 8849 students (4393 boys and 4456 girls) in three consecutive ESPAD surveys (2003, 2007 and 2011). RESULTS: In multivariate analysis for all three survey years the strongest predictor for prescription medication use was use of sedatives/tranquilizers without prescription (OR 6.14; CI 4.08-9.23; OR 8.16; CI4.65-14.32; OR 9.77; CI5.92-15.13). Frequent drinking and excessive drinking or drunkenness also predicted prescription medication use, (OR 1.85; CI1.10-3.10; OR 2.01: CI 1.20-3.39). Among other problem behaviours lower school performance (OR 2.92; CI 1.41-6.05; OR 2.56; CI 1.12-5.87), missed school days OR 1.59; OR1.01-2.51; OR1.72; CI 1.03-2.87), aggressive behaviour (OR 1.532; CI 1.01-2.28; OR1.65; CI 1.04-2.62), depressive symptoms (OR 2.19; CI 1.24-3.85) and poorer financial situation were connected with prescription medication use. CONCLUSION: Prescription use of tranquilizers/sedatives was predicted by nonmedical tranquilizers/sedatives use, alcohol abuse, symptoms of depression and variables indicating maladjusted behaviour. Although there is sufficient evidence that prescription medication abuse might went unobserved, the further analysis which could better explain its' role and impact is still needed.

Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders.

BACKGROUND: Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment for schizophrenia. OBJECTIVES: To evaluate the effects of flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes. SEARCH METHODS: We identified relevant trials by searching the Cochrane Schizophrenia Group Trials Register in March 2009 and then for this update version, a search was run in April 2013. The register is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared with placebo or other antipsychotic drugs were included. All clinically relevant outcomes were sought. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed trial quality and extracted data. For dichotomous data we estimated risk ratios (RR) with 95% confidence intervals (CI) using a fixed-effect model. Analysis was by intention-to-treat. We summated normal continuous data using mean difference (MD), and 95% CIs using a fixed-effect model. We presented scale data only for those tools that had attained prespecified levels of quality. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) we created 'Summary of findings tables and assessed risk of bias for included studies. MAIN RESULTS: The review currently includes 15 randomised controlled trials with 626 participants. No trials compared flupenthixol decanoate with placebo.One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). Only two outcomes were reported with this single study, and it demonstrated no clear differences between the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00, CI 0.33 to 27.23,very low quality evidence) and requiring anticholinergic medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality evidence).Ten studies in total compared flupenthixol decanoate with other depot preparations, though not all studies reported on all outcomes of interest. There were no significant differences between depots for outcomes such as relapse at medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence), and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to 1.23, low quality evidence). There was no difference in numbers of participants leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76 to 1.99, low quality evidence) nor with numbers of people requiring anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI 0.75 to 2.25, low quality evidence).Three studies in total compared high doses (100 to 200 mg) of flupenthixol decanoate with the standard doses (˜40mg) per injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI 0.27 to 3.69, low quality evidence) to be similar between the groups. However people receiving a high dose had slightly more favourable medium term mental state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD -10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant difference in the use of anticholinergic medications to deal with side effects at short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence). One trial comparing a very low dose of flupenthixol decanoate (˜6 mg) with a low dose (˜9 mg) per injection reported no difference in relapse rates (n = 59, 1 RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence). AUTHORS' CONCLUSIONS: In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. From the data reported in clinical trials, it would be understandable to offer standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. However, data reported are of low or very low quality and this review highlights the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate.