Add-on exercise interventions for smoking cessation in people with mental illness: a systematic review and meta-analysis.

BACKGROUND: Smoking is the most common substance use disorder among people with mental illness. In contrast to people without mental illness, among whom the proportion of smokers has declined in recent decades, the proportion of smokers among people with mental illness remains high. There is a growing body of literature suggesting the use of exercise interventions in combination with smoking cessation in people without mental illness, but to our knowledge the available studies on this treatment option in people with mental illness have not been systematically reviewed. Therefore, this systematic review and meta-analysis aims to assess the effectiveness of exercise interventions as an adjunctive treatment for smoking cessation in people with mental illness. METHODS: Electronic databases (PubMed, Web of Science, PsycInfo, Sport Discus and Base) were searched for randomised controlled trials and prospective single-group studies that investigated exercise interventions in combination with smoking cessation programmes alone or in comparison with a control group in people with mental illness. A meta-analysis using the Mantel-Haenszel fixed-effect model was conducted to estimate the overall effect of treatment on smoking cessation (abstinence rate at the end of the intervention and at 6-month follow-up). RESULTS: Six studies, five randomised controlled trials and one study with a prospective single-group design, were included in the systematic review and four randomised controlled trials were included in the meta-analysis. The meta-analysis found a significantly higher abstinence rate after additional exercise at the end of the intervention [risk ratio (RR) 1.48, 95% confidence interval (CI) 1.13-1.94], but not at the 6-month follow-up (RR 1.34, 95% CI 0.89-2.04). CONCLUSIONS: Exercise appears to be an effective adjunctive therapy to temporarily increase abstinence rates in individuals with mental illness at the end of the intervention. However, due to the small number of included studies and some risk of bias in the included studies, the results should be treated with caution. Therefore, future studies with larger samples are needed to provide a more accurate estimate of the effect in people with mental illness. Registration The systematic review and meta-analysis were registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42020178630).

[Coercive interventions: historical summary and review of subjective experience]. / Zwangsmaßnahmen in der Psychiatrie: Aus der Steinzeit in eine bessere Zukunft.

Psychiatric treatment has always been associated with violence and coercion. Involuntary admission and coercive measures are still frequently occurring components in everyday clinical practice.Up to 15% of psychiatric inpatients experience coercive treatment at least once during hospital stay. Particularly patients suffering from schizophrenia, organic mental disorders and mania have a high risk for such incidents.There is an ongoing intense debate on the need and justification of coercive measures, although most clinicians and scientists currently agree that there is no alternative. Several investigations have shown that seclusion and mechanical restraint go along with physical and psychological problems affecting both, patients and staff. However, it was possible to identify aspects that could be improved: Maintaining an objective and professional communication during coercive treatment seems just as important as making comprehensible decisions. Alternative treatment options should be focus of further investigations.

Characteristics of Involuntarily Admitted Patients and Treatment Patterns Over a 21-Year Observation Period.

BACKGROUND: Patients suffering from psychiatric disorders are often treated in locked psychiatric units owing to psychomotor agitation, hostility and aggressive behavior, or suicidality. Because of legal conditions, investigations of these acutely ill patients are difficult, and many studies do not represent real-life psychiatry. In Austria, admission to a locked psychiatric unit is regulated by a national law for involuntary admission, which came into effect in 1991. The current retrospective study investigated the management of patients who were admitted involuntarily to an academic treatment center after the inauguration of this law. METHODS: Data collection comprised all admissions to a locked unit at the Department of Psychiatry, Psychotherapy and Psychosomatics of the Medical University Innsbruck in the years 1992, 1997, 2002, 2007, and 2012. Demographics, admission diagnosis, current danger posed to self or others, and the initial psychopharmacological intervention were assessed. RESULTS: The rate of admissions to a locked unit increased significantly throughout the course of the study, and the length of stay decreased from 8.57 days in 1997 to 6.43 days in 2012. Most patients received medication orally. Dosage of antipsychotics and benzodiazepines decreased throughout the investigation period. Self-endangering patients were treated with somewhat (nonsignificantly) higher benzodiazepine and significantly lower antipsychotic mean doses than patients posing danger to others. CONCLUSIONS: Although dosage of medication was reduced, the duration of stay in a locked unit decreased significantly over the investigated years. These findings suggest that a carefully considered pharmacological treatment may be at least as effective as a more aggressive approach.

Trends in pharmacological emergency treatment of patients suffering from schizophrenia over a 16-year observation period.

Patients suffering from schizophrenia are often treated in locked psychiatric units because of psychomotor agitation, hostility and aggressive behavior, or suicidality. Because of legal conditions, investigations on these acutely ill patients are difficult, and many studies do not represent 'real-life psychiatry'. This retrospective survey was conducted at the Department of Psychiatry, Psychotherapy and Psychosomatics of the Medical University, Innsbruck, Austria. Data were collected from the records of all adult inpatients suffering from a schizophrenia spectrum disorder according to the International Classification of Diseases, 10th ed. (ICD-10) (F2x) who had been admitted to a locked unit in 1997, 2002, 2007, and 2012. In addition to demographic data, diagnoses at the time of admission, length of stay at the locked unit, and psychopharmacological treatment (3 h before and following admission) were recorded. The mean length of stay at a locked unit decreased significantly from 11.8±4.43 days (mean±SD) in 1997 to 8.5±12.96 days (mean±SD) in 2012. The use of antipsychotics decreased nonsignificantly from 1997 to 2012. Despite an increasing use of second compared with first-generation antipsychotic drugs over the course of time, haloperidol was the most frequently used single compound in all investigated years except 2012. The majority of medications were administered orally. The use of benzodiazepines did not change substantially over the course of time. All in all, pharmacological emergency treatment of patients suffering from schizophrenia spectrum disorders in locked units was in line with current treatment guidelines, which recommend the use of second-generation antipsychotic drugs, monotherapy, oral application, and cautious dosing.

Why do indiviuals with schizophrenia drop out of observational clinical trials?

Randomized controlled trials (RCTs) and observational studies frequently differ with regard to study dropouts. The present naturalistic follow-up investigation aimed to shed a light on this issue by evaluating the time to and the reasons for study dropout in patients suffering from schizophrenia who started monotherapy with an oral new-generation antipsychotic. To this end, psychopathological symptoms and safety data were assessed in 194 patients who were followed up to a maximum observation period of twelve months. 9.3% of study participants completed the study. The mean time to study dropout was 2.6 ± 2.7 months with almost two thirds of patients dropping out within three months. 44.3% discontinued medication at the date of study dropout, the remainders dropped out due to withdrawal of written consent, logistic reasons, or nonappearance to the study visit ("loss to follow-up"), which were not necessarily to be equated with cessation of the antipsychotic. These findings indicate that in contrast to RCTs, dropout of observational studies is not necessarily associated with drug discontinuation. Accordingly, systematic differences between trial designs need to be considered when interpreting the results of clinical trials.

Prescribing Practice in Inpatients Versus Outpatients With Schizophrenia Initiating Treatment With Second-Generation Antipsychotics: A Naturalistic Follow-Up Study.

OBJECTIVE: The primary objective of this study was to investigate whether the choice and dosage of antipsychotic medication differ between patients with schizophrenia starting treatment in an inpatient or outpatient unit. In addition, we investigated whether the reason for the introduction of new antipsychotic medication had an impact on the treatment setting and whether the use of benzodiazepines differed between inpatients and outpatients. METHOD: From October 1997 to September 2010, patients with a schizophrenia spectrum disorder according to the International Classification of Diseases, Tenth Revision aged between 18 and 65 years were allocated to a naturalistic drug-monitoring program when starting treatment with a second-generation antipsychotic drug. Psychopathological symptoms were rated at baseline and after 1, 2, 4, and 8 weeks of treatment using the Positive and Negative Syndrome Scale. Inpatients and outpatients were compared with regard to the use of antipsychotics and benzodiazepines. To compare different drugs, chlorpromazine and diazepam equivalents were calculated. RESULTS: Lack of efficacy and side effects were the main reasons for initiating new antipsychotic medication. Combined evaluation of all antipsychotic compounds by meta-analysis resulted in a significant effect of the treatment setting, with inpatients receiving higher doses than outpatients. In addition, inpatients were prescribed benzodiazepines more often and in higher doses than outpatients. CONCLUSIONS: Both antipsychotics and benzodiazepines were prescribed at higher doses in an inpatient setting. Moreover, benzodiazepines were prescribed more frequently to inpatients. Accordingly, the treatment setting needs to be taken into consideration in treatment recommendations for schizophrenia spectrum disorders.

Therapeutic Alliance in Patients With Schizophrenia: Introduction of a New Rating Instrument.

OBJECTIVE: The quality of the patient-psychiatrist relationship can be seen as a cornerstone of adherence to medications in patients with chronic psychiatric disorders. Although therapeutic alliance in psychotherapy has been investigated broadly, it has received little attention in the context of medication adherence. The goal of this study was to develop and validate a user-friendly questionnaire for the assessment of therapeutic alliance in clinically stable outpatients with schizophrenia. METHODS: The "Brief Questionnaire on Therapeutic Alliance" (BQTA) addresses both the physician and the patient, each of whom responds to 5 items that focus on important domains of the therapeutic alliance. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and patients' attitudes toward the illness and medication were assessed using the Drug Attitude Inventory (DAI). RESULTS: A total of 61 patients who met ICD-10 criteria for schizophrenia spectrum disorders and their treating psychiatrists were included in the study. Overall, patients and psychiatrists gave high (ie, favorable) ratings on all BQTA items. The 5 patient-related items showed high internal consistency (Cronbach α=0.77), whereas physician-related items showed slightly less internal consistency (Cronbach α=0.68). The concordance between patient and physician ratings was fair, although statistically significant (κ=0.33, P=0.007). Physicians' total score on the BQTA was moderately correlated with patients' PANSS total score and with the DAI total score and its compliance subscale, whereas patients' total score on the BQTA did not correlate with DAI or PANSS scores. CONCLUSION: The BQTA was found to cover crucial aspects of the doctor-patient relationship in chronically ill individuals with schizophrenia. Further validation will shed more light on the usefulness of this questionnaire.

Bilirubin concentration correlates with positive symptoms in patients with schizophrenia.

OBJECTIVE: Besides its toxic effects, bilirubin has been demonstrated to have antioxidant properties to counteract oxidative stress, which has been suggested to play a role in the pathophysiology of schizophrenia. METHODS: This study investigated the potential association between changes in psychopathology measured by the Lindenmayer model of the Positive and Negative Syndrome Scale (PANSS) and changes in total plasma bilirubin concentrations. Data of patients with schizophrenia (ICD-10) starting monotherapy with a new-generation antipsychotic were analyzed at baseline (N = 52) and 2 (n = 40), 4 (n = 46), and 12 weeks (n = 30) after the initiation of treatment. Data were collected between December 1997 and October 2007 and analyzed retrospectively. RESULTS: The PANSS total score decreased significantly from baseline to weeks 2, 4, and 12 of treatment (all P values ≤ .001). Total plasma bilirubin concentration also dropped significantly from baseline to week 2 (P = .015) and decreased further until week 4 (P = .013); no significant decrease was observed between baseline and week 12. Spearman rank correlation revealed a significant association of bilirubin concentration with the PANSS positive (r = 0.371, P = .007) and excitement (r = 0.322, P = .020) components at baseline. No further correlations were found. From baseline to weeks 2, 4, and 12, changes in the PANSS positive component correlated significantly with changes in plasma bilirubin concentration (all P values < .05), whereas correlations between changes in the remaining PANSS components and bilirubin were less consistent. CONCLUSIONS: Assuming that positive symptoms are associated with the subjective experience of psychological distress, our findings indirectly expand the evidence on potential antioxidant properties of bilirubin in patients with schizophrenia.

Changes in psychopathology in schizophrenia patients starting treatment with new-generation antipsychotics: therapeutic drug monitoring in a naturalistic treatment setting.

Previous studies on the relationship between plasma levels of new-generation antipsychotics (NGAs) and clinical response did not account for inter- and intra-individual variability in drug levels. Therefore, the present study calculated the ratio of observed versus expected NGA plasma levels and investigated its relationship with changes in the Positive and Negative Syndrome Scale (PANSS). Data of patients starting monotherapy with a NGA were collected 2, 4, 8, and 12 weeks after initiation of treatment. Next to the assessment of changes in psychopathology (PANSS) the ratio of observed versus expected plasma level was calculated. A total number of 221 ratios were eligible for analysis. About half of them ranged from 0.5-2 and were considered "normal", whereas the others were considered either "too low" or "too high". Psychopathological symptoms improved over the course of treatment, but changes in PANSS from baseline did not correlate significantly with the ratios of observed versus expected plasma levels at any assessment. The lack of linear correlation can be explained by the fact that 92% of the observed NGA plasma levels were at ≥ 50% of the lower limit of the therapeutic reference range, i.e., within the asymptote of the logistic plasma level-effect relationship. Accordingly, our findings indicate that the great majority of patients were treated with NGA doses that led to optimal plasma levels, based on the clinical impression of the treating psychiatrist only. Thus, calculating the ratio of observed versus expected plasma level may not be necessary in a routine clinical setting.

Measuring adherence to medication in schizophrenia: the relationship between attitudes toward drug therapy and plasma levels of new-generation antipsychotics.

BACKGROUND: Nonadherence to medication is still a major problem in the treatment of schizophrenia. The current longitudinal study investigated whether the patients' attitudes toward treatment correlated with the ratio of observed vs expected plasma levels of antipsychotic drugs as an objective measurement of adherence. METHODS: Data of patients starting monotherapy with a new-generation antipsychotic were collected 2, 4, and 12 weeks after the initiation of treatment. Next to the assessment of patients' attitudes toward medication by means of the Drug Attitude Inventory, the ratio of the observed vs expected plasma level was calculated. Antipsychotic-induced side effects were evaluated by means of the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. RESULTS: A total of 93 patients were eligible for statistical analysis. About one-half of the ratios of observed vs expected plasma levels ranged from 0.5 to 2 and were considered normal, whereas the other ratios were considered either too low (<0.5) or too high (>2). No consistent correlation between patients' attitude toward drug therapy and the individual ratios of observed vs expected plasma levels of medication was detected. This finding was not affected by side effects. CONCLUSIONS: Our results highlight the importance of recognizing the complex nature of adherence to medication in schizophrenia patients. Importantly, we found no consistent correlation between subjective and objective measures of medication adherence. Therefore, monitoring adherence to medication remains a challenge in clinical practice.

Risk of violence of inpatients with severe mental illness--do patients with schizophrenia pose harm to others?

Individuals suffering from schizophrenia are frequently considered to be dangerous. The current longitudinal chart review was carried out to investigate the diagnostic mix of patients who were admitted to the Department of Psychiatry and Psychotherapy at the Medical University Innsbruck due to risk of harm to others. The sample consisted of all adult inpatients admitted to psychiatric acute care units in the years 1992, 1997, 2002, and 2007. Data collection included diagnoses, criteria for risk of harm to others, and the use of mechanical restraint. Altogether, 7222 admissions were reviewed. Of these, 529 patients had to be admitted to a locked unit because of risk of harm to others. Among those mechanical restraint was more often used in patients with organic mental disorders, Cluster B personality disorders, and mania than in patients with schizophrenia. Patients suffering from schizophrenia with comorbid psychoactive substance use constitute a potentially harmful population and are therefore frequently admitted to locked units due to risk of harm to others. However, in the current study additional coercive measures were more commonly applied in patients suffering from personality disorders and organic mental disorders.

Treatment of psychotic and behavioral symptoms with clozapine, aripiprazole, and reboxetine in a patient with Huntington's disease.

We report on the successful use of a combined psychopharmacological treatment in a patient with Huntington's disease, at age 39, suffering from severe psychotic and behavioral symptoms. He presented with a schizophreniform psychosis accompanied by aggressive behavior leading to admission to the locked ward of our hospital. After unsatisfactory control of the psychiatric symptoms with olanzapine, risperidone, and amisulpride, we introduced aripiprazole. This did not affect the psychotic symptoms; however, led to an improvement in aggressive behavior, motivation, and even chorea. Accordingly, we choose not to switch medication but to add clozapine. Nevertheless, his delusions improved slightly, and further add-on treatment with reboxetine brought a further beneficial effect on motivation and activities of daily living. As chorea was not disabling in our patient, tetrabenazine has not yet been tried. Treatment was safe without any relevant side effects.

Attitudes of patients with schizophrenia and depression to psychiatric research: a study in seven European countries.

BACKGROUND: Relatively few studies have examined how patients with schizophrenia and depression view psychiatric research and what influences their readiness to participate. METHODS: A total of 763 patients (48% schizophrenia, 52% depression) from 7 European countries were examined using a specifically designed self-report questionnaire ["Hamburg Attitudes to Psychiatric Research Questionnaire" (HAPRQ)]. RESULTS: Most patients (98%) approved of psychiatric research, in general, at least "a little". There was a tendency to approve psychosocial rather than biological research topics (e.g. research on the role of the family by 91% of patients compared to 79% in genetics). Reasons to participate were mainly altruistic. Only a minority (28%) considered monetary incentives important. Patients wanted extensive background information and a feedback of the results; both were significantly more expressed by schizophrenia as compared to depressive patients, although these findings need to be interpreted with care because of age and gender differences between the diagnostic groups. CONCLUSION: While patients expressed discerning views of psychiatric research, only few differences were apparent between the two diagnostic groups. Patients' research priorities are not the same as those of many professionals and funding bodies. Their demonstrated critical appraisal should inform future research ensuring an increased patient role in the research process.

Prolactin levels and sexual adverse effects in patients with schizophrenia during antipsychotic treatment.

OBJECTIVE: Patients with schizophrenia often experience sexual dysfunction (SD), to which disorder-related factors like negative symptoms and nondisorder-related factors can theoretically contribute. Thus, we investigated the correlation of SD and serum prolactin level in patients with schizophrenia during antipsychotic treatment. METHODS: We included 39 patients with schizophrenia with a mean age of 34.6 years who were switched to second-generation antipsychotics into the study. Sexual adverse effects (via a specific scale) and serum prolactin levels were measured at baseline and week 4. RESULTS: In males, mean prolactin levels increased over 4 weeks at a trend level of significance. Although a high incidence of SD was reported at baseline, there were no statistically significant changes over the course of 4 weeks. At baseline, a positive correlation between diminished sexual desire and prolactin levels could be found in men, which was not found in women; at week 4, both male and female patients demonstrated a positive correlation between orgastic dysfunction and prolactin levels. We found significant positive correlations between changes in prolactin levels over 4 weeks and changes in orgastic dysfunction for both sexes. Regression analyses showed prolactin levels at baseline to be a predictor of diminished sexual desire in men. Change in prolactin level was found to be a predictor of change for diminished sexual desire in women and for orgastic dysfunction in both sexes. CONCLUSION: We conclude that the potential of antipsychotics to increase serum prolactin levels imposes a certain risk that patients will experience SD of varying severity.

Attitudes of patients with schizophrenia and depression towards psychiatric research.

The success of clinical research depends heavily on patients' willingness to participate in studies. In recent years much work has been dedicated to studying the problems of conducting research in psychiatry, mainly in schizophrenia patients. In an attempt to replicate previous findings and extend results beyond schizophrenia, we interviewed patients suffering from schizophrenia or depression in a large academic centre concerning their attitudes towards psychiatric research. Ninety-five patients with a diagnosis of schizophrenia (48) or depression (47) completed the "Hamburg General Attitudes to Psychiatric Research Questionnaire" self-report instrument. Furthermore, demographic and clinical data were collected. Illness severity was evaluated using Clinical Global Impression and Global Assessment of Functioning scores. In general, patients approved of psychiatric research, and attitudes towards specific areas of research and research methods were rather positive. There were no significant differences between the two diagnostic groups regarding reasons for participation or non-participation in a clinical trial. The theoretical willingness to participate in studies was highest for studies using a questionnaire. Receiving sufficient information about a study before taking part was stated to be highly important. Our findings confirm and extend those of other groups. This should encourage psychiatrists at least in academic settings where most of this research has been done to approach patients to take part in clinical research.

Factors influencing the choice of new generation antipsychotic medication in the treatment of patients with schizophrenia.

OBJECTIVE: This prospective, naturalistic study investigated the factors influencing physicians' choice of antipsychotic drug therapy in the treatment of patients with schizophrenia. METHOD: 108 in- and outpatients treated at the Department of Psychiatry of the Medical University Innsbruck who started treatment with a new generation antipsychotic (except clozapine) were included. The following factors were investigated: sociodemographic and illness-related variables, pretreatment, the reasons for change of treatment (lack of efficacy, side effects, non-compliance), side effects of pretreatment and body-mass-index (BMI). RESULTS: Sociodemographic and most illness-related variables did not have an influence on the physicians' choice of medication. Risperidone was more frequently prescribed in patients with severe positive symptoms than amisulpride or quetiapine. Rigidity, orthostatic dizziness and gynecomastia during pretreatment were frequently associated with starting patients on ziprasidone. In patients with diminished sexual desire ziprasidone was preferred over olanzapine. Amisulpride was used more commonly than olanzapine if patients had experienced weight gain during pretreatment. Moreover, patients who were prescribed amisulpride had a significantly higher BMI in comparison to patients who were prescribed olanzapine. The reasons for current change of treatment, as well as the drug history (total number of antipsychotic drugs prescribed during the course of the illness) did not have an influence on the physicians' choice of antipsychotic. CONCLUSION: In summary, the data suggest that side effects have a larger influence on the choice of antipsychotic than demographic or illness-related variables, except the severity of positive symptoms.

Facial emotion recognition and its relationship to symptomatic, subjective, and functional outcomes in outpatients with chronic schizophrenia.

Outcome in schizophrenia is multidimensional and consists of clinical and psychosocial domains. Difficulties in affect recognition are a hallmark of schizophrenia, but there is little research investigating the consequences of this deficit on patients' psychosocial status. This cross-sectional study examined the relationship of facial affect recognition and treatment outcomes in terms of psychopathology, quality of life (QOL), and psychosocial functioning. We investigated 40 regular attendees of a specialized schizophrenia outpatient clinic who had been stable both from a symptomatic and a medication perspective for a minimum of 6 months and 40 healthy volunteers who were chosen to match patients in age, sex, and education. Affect recognition was positively associated with patients' level of education and negatively with increasing age. Deficits in this area corresponded to the severity of negative and affective symptoms as well as to poor work and global functioning. These findings suggest that affect recognition is an important aspect of psychosocial functioning in stable outpatients with schizophrenia.

Alterations of glucose metabolism during treatment with clozapine or amisulpride: results from a prospective 16-week study.

Although second-generation antipsychotics have notable benefits as compared to typical antipsychotics, their use has been associated with metabolic disturbances, such as alterations of glucose homeostasis. It is still being debated whether this is a class effect of second-generation antipsychotics. We conducted a prospective, open study comparing body weight, parameters of insulin resistance in schizophrenia patients treated with either clozapine (n = 10) or amisuLpride ( n = 12). All parameters were assessed monthly over a period of 12 to 16 weeks. Body mass index (BMI), fasting serum insulin levels and the Homeostasis Model Assessment (HOMA) index for insulin resistance increased significantly in patients treated with clozapine. None of these parameters increased significantly in patients treated with amisulpride. This study indicates that treatment with clozapine appears to have a higher risk to lead to metabolic disturbances than amisupride.