Christine Rummel-Kluge

Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis

OBJECTIVE The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine. METHOD We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis. RESULTS We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine. CONCLUSIONS Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient.

A Meta-Analysis of Head-to-Head Comparisons of Second-Generation Antipsychotics in the Treatment of Schizophrenia

OBJECTIVE Whether there are differences in efficacy among second-generation antipsychotics in the treatment of schizophrenia is a matter of heated debate. The authors conducted a systematic review and meta-analysis of blinded studies comparing second-generation antipsychotics head-to-head. METHOD Searches of the Cochrane Schizophrenia Groups register (May 2007) and MEDLINE (September 2007) were conducted for randomized, blinded studies comparing two or more of nine second-generation antipsychotics in the treatment of schizophrenia. All data were extracted by at least three reviewers independently. The primary outcome measure was change in total score on the Positive and Negative Syndrome Scale; secondary outcome measures were positive and negative symptom subscores and rate of dropout due to inefficacy. The results were combined in a meta-analysis. Various sensitivity analyses and metaregressions were used to examine bias. RESULTS The analysis included 78 studies with 167 relevant arms and 13,558 participants. Olanzapine proved superior to aripiprazole, quetiapine, risperidone, and ziprasidone. Risperidone was more efficacious than quetiapine and ziprasidone. Clozapine proved superior to zotepine and, in doses >400 mg/day, to risperidone. These differences were due to improvement in positive symptoms rather than negative symptoms. The results were rather robust with regard to the effects of industry sponsorship, study quality, dosages, and trial duration. CONCLUSIONS The findings suggest that some second-generation antipsychotics may be somewhat more efficacious than others, but the limitations of meta-analysis must be considered. In tailoring drug treatment to the individual patient, small efficacy superiorities must be weighed against large differences in side effects and cost.

Antipsychotic Combinations vs Monotherapy in Schizophrenia: A Meta-analysis of Randomized Controlled Trials

CONTEXT Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia. OBJECTIVE To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia. DATA SOURCES Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings. STUDY SELECTION Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic. DATA EXTRACTION AND ANALYSIS Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated. RESULTS In 19 studies (1229 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63-0.90, P = .002, NNT = 7, CI = 4-17, P = .0008, I(2) = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54-0.78, P < .00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P = .006) and less than minimally (P = .01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration >10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant. CONCLUSIONS In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research.

Alliances against depression - A community based approach to target depression and to prevent suicidal behaviour.

Depressive disorders as well as fatal and non-fatal suicidal behaviour continue to be important mental health issues. Because of the close relation between depression and suicidal behaviour, it is likely that preventive actions improving care and optimising treatment for depressed patients result in a reduction of suicidal acts. This was shown in the Nuremberg Alliance against Depression, a two-year four-level community based intervention program associated with a 24% reduction of suicidal acts (completed and attempted suicides combined) compared to a baseline year and a control region. Serving as a model project, this approach has up to now been adopted in more than 100 regions in Germany and Europe. Within the suicide prevention project OSPI-Europe, the four-level-approach was optimized and further implemented and evaluated in different European regions.

Psychoeducation for patients with schizophrenia and their families

In this review, the current evidence for the efficacy of psychoeducation, a nonpharmacological treatment strategy in the treatment of patients with schizophrenia and their families, is assessed by summarizing meta-analyses/reviews and important single studies published after the recent meta-analyses. It was found that psychoeducation for patients with schizophrenia and their families can reduce the relapse rates of these patients; long-term family interventions (i.e., with durations of more than 3 months) are particularly helpful. However, there are still unsolved questions in this area. Therefore, future research needs are a further focus of this review; for example, on the questions of how to adapt programs for stable outpatients and their families, and the minimum effective dose of psychoeducation. Finally, new approaches in the area of psychoeducation, such as including quality-of-life issues, offering psychoeducation formats for combined diagnoses, family and patient peer-to-peer programs, and focusing on gender aspects are discussed.

The role of socio-economic status in depression: results from the COURAGE (aging survey in Europe)

BackgroundLow socio-economic status (SES) has been found to be associated with a higher prevalence of depression. However, studies that have investigated this association have been limited in their national scope, have analyzed different components of SES separately, and have not used standardized definitions or measurements across populations. The aim of the current study was to evaluate the association between SES and depression across three European countries that represent different regions across Europe, using standardized procedures and measurements and a composite score for SES.MethodNationally-representative data on 10,800 individuals aged ≥18 from the Collaborative Research on Ageing in Europe (COURAGE) survey conducted in Finland, Poland and Spain were analyzed in this cross-sectional study. An adapted version of the Composite International Diagnostic Interview was used to identify the presence of depression, and SES was computed by using the combined scores of the total number of years educated (0–22) and the quintiles of the country-specific income level of the household (1–5). Multivariable logistic regression was used to assess the association between SES and depression.ResultsFindings reveal a significant association between depression and SES across all countries (p ≤ 0.001). After adjusting for confounders, the odds of depression were significantly decreased for every unit increase in the SES index for Finland, Poland and Spain. Additionally, higher education significantly decreased the odds for depression in each country, but income did not.ConclusionThe SES index seems to predict depression symptomatology across European countries. Taking SES into account may be an important factor in the development of depression prevention strategies across Europe.

Negative perceptions of ageing predict the onset and persistence of depression and anxiety: Findings from a prospective analysis of the Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND Although there is a growing literature on the adverse health outcomes related with negative ageing perceptions, studies on their association with mental disorders such as depression and anxiety are scarce. Thus, the aim of the current study was to prospectively assess the association between negative ageing perceptions and incident/persistent depression and anxiety using nationally representative data from Ireland. METHODS Data from two consecutive waves of the Irish Longitudinal Study on Ageing (TILDA) were analysed. The analytical sample consisted of 6095 adults aged ≥50 years. Validated scales for negative ageing perceptions, depression, and anxiety were used. Multivariable logistic regression analyses were used to assess the association between negative ageing perceptions at baseline and the onset and persistence of depression and anxiety at two-year follow up. RESULTS After adjusting for potential confounders, negative ageing perceptions at baseline predicted the new onset of depression and anxiety at follow-up. Among those with depression or anxiety at baseline, negative ageing perceptions also predicted the persistence of these conditions at follow-up. LIMITATIONS Baseline data on negative ageing perceptions were used for the analysis and it is possible that scores could have changed over time. CONCLUSIONS Addressing negative perceptions towards ageing by developing interventions that activate positive ageing perceptions, and target societal attitudes by means of policy change, public campaigns, and community education programmes, may shift social perceptions and reduce the burden of depression and anxiety among the elderly.

Olanzapine and clozapine differently affect sleep in patients with schizophrenia: Results from a double-blind, polysomnographic study and review of the literature

Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.

Mental health related Internet use among psychiatric patients: a cross-sectional analysis

BackgroundThe Internet is of great importance in today’s health sector, as most Internet users utilize online functions for health related purposes. Concerning the mental health care sector, little data exist about the Internet use of psychiatric patients. It is the scope of this current study to analyze the quantity and pattern of Internet usage among mental health patients.MethodsPatients from all services of the Department of Psychiatry at a university hospital were surveyed by completing a 29-item questionnaire. The data analysis included evaluation of frequencies, as well as group comparisons.Results337 patients participated in the survey, of whom 79.5% were Internet users. Social media was utilized by less than half of the users: social networks (47.8%), forums (19.4%), chats (18.7%), blogs (12.3%). 70.9% used the Internet for mental health related reasons. The contents accessed by the patients included: information on mental disorders (57.8%), information on medication (43.7%), search for mental health services (38.8%), platforms with other patients (19.8%) and platforms with mental health professionals (17.2%).Differences in the pattern of use between users with low, medium and high frequency of Internet use were statistically significant for all entities of social media (p < 0.01), search for mental health services (p = 0.017) and usage of platforms with mental health professionals (p = 0. 048).The analysis of differences in Internet use depending on the participants’ type of mental disorder revealed no statistically significant differences, with one exception. Regarding the Internet’s role in mental health care, the participants showed differing opinions: 36.2% believe that the Internet has or may have helped them in coping with their mental disorder, while 38.4% stated the contrary.ConclusionsMost psychiatric patients are Internet users. Mental health related Internet use is common among patients, mainly for information seeking. The use of social media is generally less frequent. It varies significantly between different user types and was shown to be associated with high frequency of Internet use. The results illustrate the importance of the Internet in mental health related contexts and may contribute to the further development of mental health related online offers.

Frequency and relevance of psychoeducation in psychiatric diagnoses: Results of two surveys five years apart in German-speaking European countries

BackgroundPsychoeducation has been shown to reduce relapse rates in several psychiatric disorders. Studies investigating for which psychiatric diagnoses psychoeducation is offered and assessing its perceived relevance compared to other interventions are lacking.MethodsA two-part questionnaire addressing these questions was sent to the heads of all psychiatric hospitals in Germany, Austria and Switzerland. Results were compared with those from a similar survey 5 years earlier.Results289 of 500 (58%) institutions responded. Significantly (p = 0,02) more institutions (93%) offer any type of psychoeducation as compared to 5 years before (86%). Psychoeducation is mainly offered for schizophrenia (86%) and depression (67%) and less frequently for anxiety disorders (18%) and substance abuse (17%). For the following specific diagnoses it is offered by less than 10% of the institutions: Personality disorder, bipolar disorder, posttraumatic stress disorder, dementia, obsessive compulsive disorder, sleeping disorders, eating disorders, schizophrenia plus substance abuse, pain, attention deficit hyperactivity disorder and early psychosis. 25% offer diagnosis-unspecific psychoeducation. ‘Pharmacotherapy’ (99%), ‘basic occupational therapy’ (95%) and ‘psychoeducation for patients’ (93%) were the therapies being most often, ‘light therapy’ (24%) and ‘sleep deprivation’ (16%) the therapies being least often perceived as relevant by the respondents when asked about the value of different interventions offered in their hospitals. Art therapy (61%) and psychoanalytically oriented psychotherapy (59%), two therapies with a smaller evidence base than light therapy or sleep deprivation, were perceived as relevant by more than the half of the respondents.ConclusionPsychoeducation for patients is considered relevant and offered frequently in German-speaking countries, however, mostly only for schizophrenia and depression. The ranking of the perceived relevance of different treatment options suggests that the evidence base is not considered crucial for determining their relevance.