Rolf R Engel

Ludwig-Maximilians-University of Munich, München, Bavaria, Germany

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Publications (88)464.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) are rating scales commonly used to assess the level of functioning in patients with schizophrenia. To understand the correspondence of scores between GAF and SOFAS, and what they mean from a clinical point of view, we examined the linkage of (a) GAF with SOFAS total scores, (b) GAF with Clinical Global Impressions Scale (CGI) and Positive and Negative Syndrome Scale (PANSS), and (c) SOFAS with CGI and PANSS. We used the equipercentile linking method to identify corresponding scores of simultaneous GAF, SOFAS, PANSS and CGI ratings in 1208 patients from a naturalistic European cohort study. Data were collected at baseline and at months 6, 12, 18 and 24. GAF and SOFAS total scores were found to be practically exchangeable. Both scales had strong negative correlations with CGI and PANSS; the linkage also suggested the presence of slight impairment in functioning even when patients are free from symptoms. These findings are important for the comparison of scores when different rating scales are used. We present a detailed conversion table in an online supplement.
    European Neuropsychopharmacology 08/2014; · 4.60 Impact Factor
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    ABSTRACT: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other antipsychotic compounds, however, low-potency antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side-effects.
    Cochrane database of systematic reviews (Online) 07/2014; 7:CD009396. · 5.70 Impact Factor
  • C Corves, R R Engel, J Davis, S Leucht
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    ABSTRACT: The aim of this study was to compare the differential response to amisulpride in patients with paranoid versus disorganized schizophrenia. We reanalyzed the original data from five different randomized drug trials comparing Brief Psychiatric Rating Scale (BPRS) scores in a database containing 427 paranoid and 296 disorganized patients with schizophrenia. Both the disorganized and the paranoid group showed a substantial improvement of the BPRS total score within the first 4 weeks. In the paranoid group, mean (±SD) BPRS reduction was 16.9 (±14.6) (t = 24.06, df = 426, P < 0.001) and in the disorganized group 17.0 (±15.9) (t = 18.49, df = 295, P < 0.001). An analysis of covariance (ancova) controlling for BPRS at baseline and the influence of different trial protocols showed significant differences between diagnostic groups (F = 13.47, df = 1, P < 0.001), Cohen's D 0.31 (CI = 0.16-0.46). Paranoid patients improved by 4.8 BPRS points more than disorganized patients (adjusted means 18.90 (CI = 17.33-20.37) for the paranoid and 14.1 (CI = 12.04 - 16.11) for the disorganized group. We conclude that amisulpride is effective in disorganized as well as in paranoid schizophrenia, but that symptom reduction in the disorganized subtype is less pronounced.
    Acta Psychiatrica Scandinavica 12/2013; · 4.86 Impact Factor
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    ABSTRACT: Missing outcome data is a major threat in meta-analytical studies of schizophrenia. Most clinical trials in psychiatry report only continuous outcome measures and express the effect of an intervention as a difference of means. However, these results are difficult to interpret for clinicians. Converting continuous data to binary response rates is one possible solution to the problem. Based on means and standard deviations for a continuous outcome, we examined the performance of an imputation method to define a dichotomous outcome using original individual patients' data from 16 randomized trials (6276 participants) comparing antipsychotic drugs in schizophrenia. We concluded that the imputed values re-captured in a reasonable degree the observed values providing a simple and practical alternative methodological choice for imputation of missing binary data in schizophrenia trials; nevertheless, the imputation method tended to introduce biases, especially for extreme risks and large treatment differences.
    Schizophrenia Research 11/2013; · 4.59 Impact Factor
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    ABSTRACT: The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03; amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56, 0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol 0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52; sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38, 0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone 0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from -0·09 for the best drug (haloperidol) to -0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to -1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to -0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses. Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines. None.
    The Lancet 06/2013; · 39.21 Impact Factor
  • S Leucht, P Rothe, J M Davis, R R Engel
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    ABSTRACT: The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) are the most frequently used scales to rate the symptoms of schizophrenia. There are many situations in which it is important to know what a given total score or a percent reduction from baseline score of one scale means in terms of the other scale. We used the equipercentile linking method to identify corresponding scores of simultaneous BPRS and PANSS ratings in 3767 patients from antipsychotic drug trials. Data were collected at baseline and at weeks 1, 2, 4 and 6. BPRS total scores of 18, 30, 40 and 50 roughly corresponded to PANSS total scores of 31, 55, 73 and 90, respectively. An absolute BPRS improvement of 10, 20, 30, 40 points corresponded to a PANSS improvement of 15, 32, 50, and 67. A percentage improvement of the BPRS total score from baseline of 19%, 30%, 40% and 50% roughly corresponded to percentage PANSS improvement of 16%, 25%, 35%, and 44%. Thus a given PANSS percent improvement was always lower than the corresponding BPRS percent improvement, on the average by 4-5%. A reason may be the higher number of items used in the PANSS. These results are important for the comparison of trials that used these rating scales. We present a detailed conversion table in an online supplement.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 02/2013; · 3.68 Impact Factor
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    ABSTRACT: Little is known about the clinical relevance of the Hamilton Rating Scale for Depression (HAMD-17) total scores. It is unclear how total scores translate into clinical severity, or what commonly used measures for response (reduction from baseline of ≥50% in the total score) and remission (total HAMD-17 score ≤7) mean from a clinical perspective. We therefore compared: (a) the percentage and absolute change in the HAMD-17 total scores with Clinical Global Impression-Improvement (CGI-I); (b) the absolute and percentage change in the HAMD-17 total scores with Clinical Global Impression-Severity (CGI-S) absolute change; and (c) the percentage and absolute change in the HAMD-17 total scores with CGI-I in the subgroups of patients with≤median and>median HAMD-17 total scores at baseline. The method used was equipercentile linking of HAMD-17 and CGI ratings from 43 drug trials in patients with Major Depressive Disorder (MDD) (n=7131). Our results confirm the validity of the commonly used measures for remission and response in MDD trials: a CGI-I score of 2 ('much improved') corresponded to a reduction from baseline of >50% and <60%, and a CGI-I score of 1 ('very much improved') to a reduction of >75% and <85%. The CGI-S score of 1 ('normal., not at all ill') corresponded to the HAMD-17 total score of <5 and the CGI-S score of 2 ('borderline mentally ill') to the score between 6 and 8. An effect of baseline illness severity was observed.
    Journal of affective disorders 01/2013; · 3.76 Impact Factor
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    ABSTRACT: In this study, a functional magnetic resonance imaging paradigm originally employed by Takahashi et al. (2004) was adapted to look for emotion-specific differences in functional brain activity within a healthy German sample (N=14), using shame- and guilt-related stimuli and neutral stimuli.Activations were found for both of these emotions in the temporal lobe (shame condition: Anterior cingulate cortex, parahippocampal gyrus; guilt: Fusiform gyrus, middle temporal gyrus). Specific activations were found for shame in the frontal lobe (medial and inferior frontal gyrus), and for guilt in the amygdala and insula. This is consistent with Takahashi et al.'s (2004) results obtained for a Japanese sample (using Japanese stimuli), which showed activations in the fusiform gyrus, hippocampus, middle occipital gyrus and parahippocampal gyrus.During the imagination of shame, frontal and temporal areas (e.g. middle frontal gyrus and parahippocampal gyrus) were responsive regardless of gender. In the guilt condition, women only activate temporal regions, whereas men showed additional frontal and occipital activation as well as a responsive amygdala.The results suggest that shame and guilt share some neural networks, as well as having individual areas of activation. It can be concluded that frontal, temporal and limbic areas play a prominent role in the generation of moral feelings.
    Social Cognitive and Affective Neuroscience 10/2012; · 5.04 Impact Factor
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    ABSTRACT: Recent analyses tried to explain the meaning of the Brief Psychiatric Rating Scale total score (BPRS) and its percentage change from baseline by equipercentile linking with the Clinical Global Impression Scale (CGI). A major limitation was that they were conducted in clinical trial populations limiting generalisability to 'real-world' patients. We therefore replicated the findings in a large sample covering patients admitted to a state hospital with a catchment area. BPRS and CGI ratings at admission (n=1772) and at discharge from all patients with schizophrenic disorders (ICD-10 F20.0-F20.9) admitted between 2005 and 2008 were compared using equipercentile linking. Being considered "mildly ill" according to the CGI severity score approximately corresponded to a BPRS total score of 25, "moderately ill" to a BPRS of 33-35, "markedly ill" to a BPRS of 50 and severely ill to a BPRS of 70. To be "minimally improved" according to the CGI change score was associated with a mean BPRS reduction of 13%; and "much improved" with 50% BPRS reduction. The linking functions were not identical, but overall comparable to those in previous randomised trial samples. The suggestion that a 50% BPRS reduction from baseline is a clinically meaningful definition of response in acutely ill patients was reinforced.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 02/2012; 22(7):501-5. · 3.68 Impact Factor
  • Source
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) persists frequently into adulthood. The decomposition of endophenotypes by means of experimental neuro-cognitive assessment has the potential to improve diagnostic assessment, evaluation of treatment response, and disentanglement of genetic and environmental influences. We assessed four parameters of attentional capacity and selectivity derived from simple psychophysical tasks (verbal report of briefly presented letter displays) and based on a "theory of visual attention." These parameters are mathematically independent, quantitative measures, and previous studies have shown that they are highly sensitive for subtle attention deficits. Potential reductions of attentional capacity, that is, of perceptual processing speed and working memory storage capacity, were assessed with a whole report paradigm. Furthermore, possible pathologies of attentional selectivity, that is, selection of task-relevant information and bias in the spatial distribution of attention, were measured with a partial report paradigm. A group of 30 unmedicated adult ADHD patients and a group of 30 demographically matched healthy controls were tested. ADHD patients showed significant reductions of working memory storage capacity of a moderate to large effect size. Perceptual processing speed, task-based, and spatial selection were unaffected. The results imply a working memory deficit as an important source of behavioral impairments. The theory of visual attention parameter working memory storage capacity might constitute a quantifiable and testable endophenotype of ADHD.
    Journal of Abnormal Psychology 08/2011; 120(4):890-901. · 4.86 Impact Factor
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    ABSTRACT: Hyponatraemia (HN) can be a life-threatening medical condition which may lead to severe neurological and psychiatric symptoms. The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicentre drug surveillance programme that assesses severe or new adverse drug reactions during psychopharmacological treatment in psychiatric inpatients. We report on a total of 263 864 psychiatric inpatients monitored from 1993 to 2007 in 80 psychiatric hospitals in Germany, Switzerland and Austria. During this period plasma sodium levels below 130 mmol/l (severe HN according to AMSP) were reported in 93 patients (relative frequency 0.04%). On average, the plasma sodium levels of all cases were 119.7 mmol/l (±5.8 s.d.); median 121 mmol/l (range 104-129 mmol/l). Patients who showed no clinical signs (n=65, 70%) had a mean sodium level of 121.3 mmol/l (±5.0 s.d.); median 122 mmol/l (range 114-129 mmol/l). By contrast, patients with clinical symptoms (n=28, 30%) had a mean sodium level of 116.0 mmol/l (±6.0 s.d.); median 117 mmol/l (range 104-125 mmol/l). HN was mainly observed during treatment with selective serotonin reuptake inhibitors (SSRIs) (0.06%), Serotonin noradrenaline reuptake inhibitors (SNRIs) (0.08%), carbamazepine (0.10%) and oxcarbazepine (1.29%); the highest rate was found for oxcarbazepine. Antipsychotics, mirtazapine and tricyclic antidepressants were only rarely involved in HN (0.003-0.005%). Combinations of several drugs known to induce HN significantly increased the risk of HN, e.g. more than 10-fold for SSRI+diuretics+ACE inhibitors (0.37%) vs. SSRI given alone (0.02%). This is clinically relevant because such combinations, e.g. SSRI+diuretics may occur especially in elderly patients, who are in general at higher risk of developing HN.
    The International Journal of Neuropsychopharmacology 07/2011; 15(6):739-48. · 5.64 Impact Factor
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    ABSTRACT: While international guidelines recommend monotherapy with antidepressants for depressed patients, recent investigation has demonstrated augmenting effects of antipsychotics (APs) in patients with major depression. We set out to investigate the use of APs in a European sample of depressed inpatients and the possible changes in their prescription over the period from 2000 to 2007. On two reference days in the years 2000 (32 psychiatric institutions, N=1078) and 2007 (54 psychiatric institutions, N=1826), the following data were recorded for all depressed inpatients (ICD-10: F32.00, F32.01, F32.1, F32.10, F32.11, F32.2, F33.0, F33.00, F33.01, F33.1, F33.10, F33.11, F33.2), monitored as part of the AMSP (Arzneimittelsicherheit in der Psychiatrie) surveillance programme: age, sex, ICD-10 diagnosis and all medication applied on that day. Depressed inpatients with psychotic symptoms were excluded. We found a significant increase in the number of AP-treated inpatients from 37.9% in 2000 to 45.8% in 2007 (χ²=17.257, p<0.001). The number of inpatients who received an atypical AP rose significantly between 2000 and 2007, from 12.8% to 28.3% (χ²=93.37, p<0.001). On the contrary, the percentage of inpatients receiving typical APs showed a significant decrease from 30.2% to 24.1% over the same period (χ²=13.179, p<0.001). Examining only the subgroup of severely depressed inpatients we found an increase in the number of AP-treated inpatients, but this was not statistically significant (χ²=2.047, p=0.15). Our study revealed a significant increase in the usage of atypical APs. However, this effect was not only due to augmentation strategies for severely depressed inpatients. Further studies are needed to examine possible putative effects of AP augmentation treatment in mild to moderate depression.
    The International Journal of Neuropsychopharmacology 05/2011; 15(4):449-57. · 5.64 Impact Factor
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    ABSTRACT: A range of psychological theories have been proposed to account for the experience of auditory hallucinations and delusions in schizophrenic patients. Most influential theories are those implicating the defective self-monitoring of inner speech. Some recent studies measured response bias independently of self-monitoring and found the results inconsistent with the defective self-monitoring model, but explained by an externalizing response bias. We aimed to investigate the role of attentional bias in external misattribution of source by modulating participant's endogenous expectancies. Comparisons were made between patients with paranoid schizophrenia (N=23) and matched healthy controls (N=23) who participated in two different versions of an audio-visual task, which differed based upon level of the cue predictiveness. The acoustic characteristic of voice was altered in half of the trials by shifting the pitch (distortion). Participants passively listened to recordings of single adjectives spoken in their own and another person's voice (alien) preceded by their own or another person's (alien) face and made self/non self judgments about the source. The patients showed increased error rates comparing to controls, when listening to the distorted self spoken words, misidentifying their own speech as produced by others. Importantly, patients made significantly more errors across all the invalid cue conditions. This suggests not only the presence of pathological misattribution bias, but also an inadequate balance between top-down and bottom-up attentional processes in the patients, which could be responsible for misattribution of the ambiguous sensory material.
    Neuropsychologia 01/2011; 49(5):805-12. · 3.48 Impact Factor
  • European Psychiatry - EUR PSYCHIAT. 01/2011; 26:591-591.
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    ABSTRACT: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic compounds, however, low-potency antipsychotic drugs are often clinically perceived as less efficacious than high-potency compounds, and they also seem to differ in their side-effects.
    The Cochrane Library, 01/2011;
  • European Psychiatry - EUR PSYCHIAT. 01/2011; 26:194-194.
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2011; 21.
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    ABSTRACT: Linking of the Clinical Global Impression (CGI) Scale and the Positive and Negative Syndrome Scale (PANSS) was performed within a naturalistic sample. Furthermore, these linking results were compared with those derived from randomized controlled trials to examine if the baseline severity might influence the linking results. Biweekly PANSS and CGI ratings were performed from admission to discharge in 398 schizophrenia patients treated within a naturalistic study. Equipercentile linking was performed using the statistical program, R 2.8.1. To evaluate how the naturalistic study design would influence linkage results, a so-called study sample was computed with patients of the naturalistic study fulfilling common inclusion criteria of randomized controlled trials (n = 199). Patients not fulfilling these criteria (less ill sample) and those fulfilling the criteria (study sample) were compared using confidence intervals. We found a considerable difference between the linking of the CGI severity score and the PANSS total score comparing the less ill sample and the study sample. Being considered "mildly ill" at admission in the less ill sample corresponded to a PANSS total score of 47 points and to a PANSS total score of 67 points in the study sample. Considering the linking of the CGI improvement score and PANSS changes, similar results were found for CGI improvement ratings ranging from "very much improved" to "minimally improved". Despite considerable differences, a 50% PANSS reduction was found to correspond to a clinical rating of much improved, which seems to be a suitable definition for response in clinical drug trials.
    Journal of clinical psychopharmacology 12/2010; 30(6):726-31. · 5.09 Impact Factor
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    ABSTRACT: Background: Linking of the Clinical Global Impression (CGI) Scale and the Positive and Negative Syndrome Scale (PANSS) was performed within a naturalistic sample. Furthermore, these linking results were compared with those derived from randomized controlled trials to examine if the baseline severity might influence the linking results. Methods: Biweekly PANSS and CGI ratings were performed from admission to discharge in 398 schizophrenia patients treated within a naturalistic study. Equipercentile linking was performed using the statistical program, R 2.8.1. To evaluate how the naturalistic study design would influence linkage results, a so-called study sample was computed with patients of the naturalistic study fulfilling common inclusion criteria of randomized controlled trials (n = 199). Patients not fulfilling these criteria (less ill sample) and those fulfilling the criteria (study sample) were compared using confidence intervals. Results: We found a considerable difference between the linking of the CGI severity score and the PANSS total score comparing the less ill sample and the study sample. Being considered "mildly ill" at admission in the less ill sample corresponded to a PANSS total score of 47 points and to a PANSS total score of 67 points in the study sample. Considering the linking of the CGI improvement score and PANSS changes, similar results were found for CGI improvement ratings ranging from "very much improved" to "minimally improved." Conclusions: Despite considerable differences, a 50% PANSS reduction was found to correspond to a clinical rating of much improved, which seems to be a suitable definition for response in clinical drug trials.
    Journal of Clinical Psychopharmacology 11/2010; 30(6):726-731. · 3.51 Impact Factor
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    ABSTRACT: Since the advent of antidepressant drug treatment, the question of whether these substances induce suicidal ideation and behavior has not been satisfactorily answered. The aim of this study is to contribute to this ongoing discussion by taking a heuristic case-based approach to the question. A large data set from a European drug surveillance program (Arzneimittelsicherheit in der Psychiatrie; AMSP) performed in 85 psychiatric hospitals from 1993 until 2008 was analyzed. A series of single cases were carefully assessed. The observed frequencies of adverse drug reactions (ADRs) in this sample were related to the total AMSP population, who used the imputed medication. A total of 142,090 adult patients taking antidepressant medication were observed. Thirty-three incidents of suicidality (12 cases of suicidal ideation, 18 attempts, and 3 completed suicides) were documented. Fourteen cases were assumed to be probably, and 19 to be possibly, related to the drug. Twenty-three cases judged as suicidal ADRs were associated with restlessness, 10 with ego-dystonia, 9 with impulsiveness, and 3 with psychosis. A higher incidence of suicidal ADRs was observed for selective serotonin reuptake inhibitors (0.034%; 95% CI, 0.020-0.054) and serotonin-norepinephrine reuptake inhibitors (0.034%; 95% CI, 0.015-0.068) compared to noradrenergic and specific serotonergic antidepressants (0.009%; 95% CI, 0.002-0.027) and tricyclic antidepressants (0.002%; 95% CI, 0.000-0.014). Despite the methodological limitations of this study, the large AMSP data set supports the assumption that antidepressant drugs rarely trigger suicidality.
    The Journal of Clinical Psychiatry 10/2010; 71(10):1293-307. · 5.81 Impact Factor

Publication Stats

3k Citations
464.72 Total Impact Points

Institutions

  • 2001–2014
    • Ludwig-Maximilians-University of Munich
      • • Department of Psychiatry
      • • Hospital and Clinic of Psychiatry and Psychotherapy Poli
      München, Bavaria, Germany
  • 2001–2013
    • Technische Universität München
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie
      München, Bavaria, Germany
  • 2007–2011
    • Medical University of Vienna
      • Department of Psychiatry and Psychotherapy
      Wien, Vienna, Austria
  • 2008
    • Bar Ilan University
      Gan, Tel Aviv, Israel
    • Nagoya City University
      • Department of Psychiatry and Cognitive-Behavioral Medicine
      Nagoya, Aichi, Japan
  • 2002
    • Deutsches Herzzentrum München
      München, Bavaria, Germany