Two Sides of the Same Coin in Female Borderline Personality Disorder: Self-Reported Guilt and Shame and Their Neurofunctional Correlates.

OBJECTIVE: Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD. METHODS: Twenty patients with BPD and twenty healthy controls (HCs) took part in an experiment that induced shame and guilt by imagining scenarios during scanning using functional brain imaging. Participants also filled out self-report questionnaires and took part in diagnostic interviews. RESULTS: BPD patients reported more proneness to guilt but not to shame than the HCs. There was no difference in the self-reported intensity rating of experimentally induced emotions between the groups. Between-group contrast of neural signals in the shame condition revealed a stronger activation of cingulate and fusiform gyrus for the BPD patients compared to the controls, and a more pronounced activation in the lingual gyrus and cuneus for the HCs. In the guilt condition, activation in the caudate nucleus, the fusiform gyrus, and the posterior cingulate cortex was stronger in BPD patients, while HC showed stronger activations in cuneus, lingual gyrus, and fronto-temporal regions. CONCLUSIONS: Differences in the neuro-functional processes between BPD patients and HC were found, even though the two groups did not differ in their self-report of subjective proneness to guilt and emotional intensity of shame and guilt during the experiment. While the HCs may be engaged more by the emotional scenarios themselves, the BPD patients may be more occupied with cognitive regulatory and self-referential processing.

Two Sides of Theory of Mind: Mental State Attribution to Moving Shapes in Paranoid Schizophrenia Is Independent of the Severity of Positive Symptoms.

BACKGROUND: Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others' mental states (overmentalizing). METHODS: Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia. RESULTS: In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample. CONCLUSIONS: Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia.

Understanding effect size: an international online survey among psychiatrists, psychologists, physicians from other medical specialities, dentists and other health professionals.

BACKGROUND AND OBJECTIVE: Various ways exist to display the effectiveness of medical treatment options. This study examined various psychiatric, medical and allied professionals' understanding and perceived usefulness of eight effect size indices for presenting both dichotomous and continuous outcome data. METHODS: We surveyed 1316 participants from 13 countries using an online questionnaire. We presented hypothetical treatment effects of interventions versus placebo concerning chronic pain using eight different effect size measures. For each index, the participants had to judge the magnitude of the shown effect, to indicate how certain they felt about their own answer and how useful they found the given effect size index. FINDINGS: Overall, 762 (57.9%) participants fully completed the questionnaire. In terms of understanding, the best results emerged when both the control event rate (CER) and the experimental event rate (EER) were presented. The difference in minimal importance difference units (MID unit) was understood worst. Respondents also found CER and EER to be the most useful presentation approach while they rated MID unit as the least useful. Confidence in the risk ratio ranked high, even though it was rather poorly understood. CONCLUSIONS AND CLINICAL IMPLICATIONS: For dichotomous outcomes, presenting the effects in terms of the CER and EER could lead to the most correct interpretation. Relative measures including the risk ratio must be supplemented with absolute measures such as the CER and EER. Effects on continuous outcomes were better understood through standardised mean differences than mean differences. These can also be supplemented by dichotomised CER and EER.

Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis.

BACKGROUND: There is no consensus on defining relapse in schizophrenia, and scale-derived criteria with unclear clinical relevance are widely used. We aimed to develop an evidence-based scale-derived set of criteria to define relapse in patients with schizophrenia or schizoaffective disorder. METHODS: We searched the Yale University Open Data Access (YODA) for randomised controlled trials (RCTs) in clinically stable adults with schizophrenia or schizoaffective disorder, and obtained individual participant data on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity (CGI-S), Personal and Social Performance (PSP), and Social and Occupational Functioning Assessment Scale (SOFAS). Our main outcomes were PANSS-derived criteria based on worsening in PANSS total score. We examined their relevance using equipercentile linking with CGI-S and functioning scales, and their test-performance in defining relapse with diagnostic test accuracy meta-analysis against CGI-S worsening (≥1-point increase together with a score ≥4 points) and psychiatric hospitalisation. FINDINGS: Based on data from seven RCTs (2354 participants; 1348 men [57·3%] and 1006 women [42·7%], mean age of 39·5 years [SD 12·0, range 17-89]; 303 Asian [12.9%], 255 Black [10.8%], 1665 White [70.7%], and other or unspecified 131 [5.6%]), an increase of 12 points or more in PANSS total (range 30-210 points) corresponded to clinically important deterioration in global severity of illness (≥1 point increase in CGI-S, range 1-7) and functioning (≥10 points decline in PSP or SOFAS, range 1-100). The interpretation of percentage changes varied importantly across different baseline scores. An increase of 12 points or more in PANSS total had good sensitivity and specificity using CGI-S as reference standard (sensitivity 82·1% [95% CI 77·1-86·4], specificity 86·9% [82·9-90·3]), as well as good sensitivity but lower specificity compared to hospitalisation (sensitivity 81·7% [74·1-87·7], specificity 69·2% [60·5-76·9]). Requiring either an increase in PANSS total or in specific items for positive and disorganization symptoms further improved test-performance. Cutoffs for situations where high sensitivity or specificity is needed are presented. INTERPRETATION: An increase of either 12 points or more in the PANSS total score, or worsening of specific positive and disorganisation symptom items could be a reasonable evidence-based definition of relapse in schizophrenia, potentially linking symptoms used to define remission and relapse. Percentage changes should not be used to define relapse because their interpretation depends on baseline scores. FUNDING: German Research Foundation (grant number: 428509362).

The relationship between blood-brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis.

BACKGROUND: Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood-brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. AIMS: To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. METHOD: We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. RESULTS: Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. CONCLUSIONS: The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed.

Antipsychotic drugs and their effects on cognitive function: protocol for a systematic review, pairwise, and network meta-analysis.

BACKGROUND: There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning. METHODS: In our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings. DISCUSSION: This systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients' and physicians' decision-making processes based on the latest available evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022312483.

Neurocognitive Deficits in First-Episode and Chronic Psychotic Disorders: A Systematic Review from 2009 to 2022.

Cognitive impairment in patients suffering from schizophrenia spectrum disorders has been discussed as a strong predictor for multiple disease outcome variables, such as response to psychotherapy, stable relationships, employment, and longevity. However, the consistency and severity of cognitive deficits across multiple domains in individuals with first-episode and chronic psychotic disorders is still undetermined. We provide a comprehensive overview of primary research from the years 2009 to 2022. Based on a Cochrane risk assessment, a systematic synthesis of 51 out of 3669 original studies was performed. Impairment of cognitive functioning in patients diagnosed with first-episode psychotic disorders compared with healthy controls was predicted to occur in all assessed cognitive domains. Few overall changes were predicted for chronically affected patients relative to those in the first-episode stage, in line with previous longitudinal studies. Our research outcomes support the hypothesis of a global decrease in cognitive functioning in patients diagnosed with psychotic disorders, i.e., the occurrence of cognitive deficits in multiple cognitive domains including executive functioning, memory, working memory, psychomotor speed, and attention. Only mild increases in the frequency of cognitive impairment across studies were observed at the chronically affected stage relative to the first-episode stage. Our results confirm and extend the outcomes from prior reviews and meta-analyses. Recommendations for psychotherapeutic interventions are provided, considering the broad cognitive impairment already observed at the stage of the first episode. Based on the risk of bias assessment, we also make specific suggestions concerning the quality of future original studies.

Neurocognitive deficits in depression: a systematic review of cognitive impairment in the acute and remitted state.

Previous research suggests a broad range of deficits in major depressive disorder. Our goal was to update the current assumptions and investigate the extent of cognitive impairment in depression in the acute and remitted state. A systematic review of the existing literature between 2009 and 2019 assessing the risk of bias within the included studies was performed. Of the 42 articles reviewed, an unclear risk of bias was shown overall. The risk of bias mainly concerned the sample selection, inadequate remedial measures, as well as the lack of blinding the assessors. In the acute phase, we found strong support for impairment in processing speed, learning, and memory. Follow-up studies and direct comparisons revealed less pronounced deficits in remission, however, deficits were still present in attention, learning and memory, and working memory. A positive correlation between the number of episodes and cognitive deficits as well as depression severity and cognitive deficits was reported. The results also demonstrate a resemblance between the cognitive profiles in bipolar disorder and depression. Comparisons of depression with schizophrenia led to unclear results, at times suggesting an overlap in cognitive performance. The main findings support the global deficit hypothesis and align with results from prior meta-analyses and reviews. Recommendations for future research are also presented.

Atypical dyskinesias under treatment with antipsychotic drugs: Report from the AMSP multicenter drug safety project.

OBJECTIVES: The aim of this study was to describe atypical dyskinesias (AtypDs) occurring during treatment with antipsychotic drugs (APDs). AtypDs are dyskinesias showing either an unusual temporal relationship between onset of treatment and start of the adverse drug reaction (ADR) or an unusual presentation of clinical symptoms. METHODS: Data on the utilisation of APDs and reports of severe APD-induced AtypDs were collected using data from the observational pharmacovigilance programme - 'Arzneimittelsicherheit in der Psychiatrie (English: drug safety in psychiatry)' (AMSP) - from 1993 to 2016. RESULTS: A total of 495,615 patients were monitored, of which 333,175 were treated with APDs. Sixty-seven cases (0.020%) of severe AtypDs under treatment with APDs were registered. The diagnoses of schizophrenic disorders as well as organic mental disorders were related to significantly higher rates of AtypDs. Second-generation antipsychotic drugs (SGAs) showed slightly higher rates of AtypDs (0.024%) than high-potency (0.011%) or low-potency first-generation antipsychotic drugs (FGAs; 0.006%). In 41 cases (61.2%), two or more drugs were found to cause AtypDs. CONCLUSIONS: Our study indicates that AtypDs are rare ADRs. SGAs may have a higher risk for the occurrence of AtypDs than FGAs. Clinicians should be aware of this ADR and patients should be monitored and examined carefully.

How Efficacious Are Antipsychotic Drugs for Schizophrenia? An Interpretation Based on 13 Effect Size Indices.

BACKGROUND: The magnitude of the superiority of antipsychotics over placebo is debated. One reason is that the effect-size index which is usually used in meta-analyses is in standard deviation units. Many other indices, some of which are more intuitive, exist. METHODS: We explain the formulae, advantages, and limitations of 13 effect-size indices: Mean Difference (MD), Standardized-Mean-Difference (SMD), Correlation Coefficient, Ratio-of-Means (RoM, endpoint and change data), Improvement Fraction (IF), Drug-Response Fraction (DRF), Minimally-Clinically-Important-Difference-Units (MCIDU), Number-Needed-to-Treat-derived from SMD (NNT), Odds Ratio (OR), Relative Risk (RR), and Risk Difference (RD) derived from SMD, Drug-response and Placebo-response in percent. We applied these indices to meta-analyses comparing antipsychotic drugs with placebo for acute schizophrenia. RESULTS: The difference of all antipsychotics pooled vs placebo (105 trials with 22741 participants) was: MD 9.4 (95% CI 8.4,10.2) PANSS points, SMD 0.47 (0.42,0.51), Correlation coefficient 0.23 (0.21,0.25), RoM endpoint 0.83 (0.81,0.85), RoM change 1.94 (1.84,2.02), IF (%) 49 (46,51), DRF (%) 94 (84,102), MCIDU 0.63 (0.56,0.68), NNT 5 (5,6), OR 2.34 (2.14, 2.52), RR 1.67 (1.59,1.73), RD 20% (18-22), and 50% (48, 52) improved on drug compared to 30% on placebo. Results of individual drugs compared to placebo are presented, as well. CONCLUSIONS: Taken together these indices show a substantial, but not a large superiority of antipsychotics compared to placebo. The general chronicity of the patients in the trials must be considered. Future meta-analyses should report other effect size indices in addition to the Standardized-Mean-Difference, in particular percentage responders in the drug and placebo groups. They can be easily derived and would enhance the interpretation of research findings.

Sex differences in pharmacological treatment of major depressive disorder: results from the AMSP pharmacovigilance program from 2001 to 2017.

Data on drug prescription for outpatients with major depressive disorder (MDD) suggest women are more likely to be treated with psychotropic drugs, while data on sex differences regarding pharmacological treatment of psychiatric inpatients are currently not available. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) of 44,418 psychiatric inpatients with MDD were analyzed for sex differences between 2001 and 2017. Sex differences were analyzed using relative risks (RR) and 95% confidence intervals (95% CI). Time trends were analyzed by comparing the first (2001-2003) with the last time period (2015-2017). In general, men and women were equally likely to use psychotropic drugs. Monotherapy was more common in men. Women were more likely to utilize ≥ 4 psychotropic drugs. Antidepressant drugs (ADDs) were the most prescribed drug class. Men had a higher utilization of noradrenergic and specific serotonergic antidepressants (RR 1.15; 95% CI 1.12-1.19), especially mirtazapine (RR 1.16; 95% CI 1.12-1.19), but also of other ADDs such as bupropion (RR 1.50; 95% CI 1.35-1.68). Males had a slightly higher utilization of second-generation antipsychotic drugs (RR 1.06; 95% CI 1.03-1.09) and were less often treated with low-potency first-generation antipsychotic drugs (RR 0.86; 95% CI 0.83-0.90). Tranquilizing (e.g., benzodiazepines; RR 0.89; 95% CI 0.86-0.92) and hypnotic drugs (e.g., Z-drugs; RR 0.85; 95% CI 0.81-0.89) were less utilized in the treatment of male patients. Not all sex differences were stable over time. More sex differences were detectable in 2015-2017 than in 2001-2003. Findings suggest that certain psychotropic drugs are preferred in the treatment of men vs. women, however, sex differences found in this study are not as large as in ambulatory settings. To make evidence-based sex-specific recommendations in the treatment of MDD, differences in drug response and tolerability need to be further researched.

Time trends in pharmacological treatment of major depressive disorder: Results from the AMSP Pharmacovigilance Program from 2001-2017.

BACKGROUND: Currently available data on the prescription practice among patients with major depressive disorder (MDD) reflect the outpatient setting. This is the first study to provide information on time trends of psychotropic drug utilization in psychiatric inpatients. METHOD: Data stems from German-speaking psychiatric hospitals collected by the program "Drug Safety in Psychiatry" (Arzneimittelsicherheit in der Psychiatrie, AMSP) between 2001 and 2017. 44,418 psychiatric inpatients with MDD were included. Time trends in drug utilization were analyzed by comparing the first (2001-2003) and last time point (2015-2017) using risk ratios (RR). RESULTS: Antidepressant drugs (ADD) were the most used psychotropic drug class with utilization decreasing slightly from 2001-2003 (89.7%) to 2015-2017 (85.5%). Use of tricyclic ADDs showed the greatest decline (RR 0.35), while use of selective serotonin-noradrenaline reuptake inhibitors (RR 1.72) and "other ADDs" increased the most. Use of antipsychotic drugs (APD), especially second-generation antipsychotic drugs (RR 1.46), increased. Use of tranquilizing (RR 0.71) and hypnotic drugs (RR 0.43) both decreased. Most patients were treated with more than one psychotropic drug, most often ADD + APD, which was utilized more often in 2015-2017 (51.1%) than in 2001-2003 (45.1%; RR 1.13). Combination of two ADDs increased from 2001-2003 (24.5%) to 2015-2017 (33.0%; RR 1.35). LIMITATIONS: The cross-sectional design does not allow conclusions to be drawn about causal relationship of findings. Further, only certain clinical and sociodemographic data was available. CONCLUSION: Treatment of MDD has shown significant changes from 2001 to 2017.

Severe drug-induced liver injury in patients under treatment with antipsychotic drugs: Data from the AMSP study.

OBJECTIVES: Drug-induced liver injury (DILI) has been associated with various antipsychotic drugs (APDs). Comparative studies between individual APDs are largely not available. METHODS: Antipsychotic drug utilisation data and reports of severe antipsychotic DILI were assessed by using data from an observational pharmacovigilance programme-Arzneimittelsicherheit in der Psychiatrie (AMSP)-during the period 1993-2016. RESULTS: Of the 333,175 patients treated with APDs, a total of 246 (0.07%) events of severe DILI were identified. Phenothiazines were associated with significantly higher rates of severe DILI (0.03%, 95% CI = 0.02-0.04) than thioxanthenes (0.01%, 95% CI = 0.00-0.02) or butyrophenones (0.01%, 95% CI = 0.00-0.01). Among individual drugs, olanzapine (0.12%, 95% CI = 0.10-0.16), perazine (0.09%, 95% CI = 0.05-0.15) and clozapine (0.09%, 95% CI = 0.10-0.12 ranked highest. In 78 cases (31.7%), combination therapies with antipsychotic and antidepressant drugs or with two or more APDs were considered responsible. Male sex and a diagnosis of mania were associated with significantly higher rates of severe DILI while older patients (≥65 years old) were significantly less often affected. CONCLUSIONS: In the present analysis of a representative psychiatric inpatient cohort, olanzapine, perazine, and clozapine were the most common individual APDs associated with severe DILI.

Personality Traits in Marathon Runners and Sedentary Controls With MMPI-2-RF.

BACKGROUND: Endurance exercise in general and marathon running in particular have become increasingly popular over the past decades. Recent investigations about personality structures in this cohort and comparisons to non-active cohorts are lacking. METHODS: In the ReCaP study (Running effects on Cognition and Plasticity), a total of 100 marathon runners and 46 sedentary controls were recruited. After elimination of Minnesota Multiphasic Personality Inventory 2 Restructured Form (MMPI-2-RF) profiles with insufficient validity, 79 marathon runners (MA) and 27 sedentary controls (SC) remained for final analyses. Depressive symptoms were evaluated with Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAMD). RESULTS: Marathon runners had lower scores in scales measuring somatic and cognitive complaints, stress, demoralization, hopelessness and distrust. Within the marathon group, committed runners exhibited hypomanic traits compared to regular runners. DISCUSSION AND CONCLUSION: Personality differences could be summarized as (sub-)depressive personality traits in SC compared to MA rather than typical (sub-) depressive symptoms in the meaning of depressive disorders. Future studies should further evaluate cause and consequence of endurance training and hypomanic or euthymic symptoms, as a two-way interaction exists. TRIAL REGISTRATION: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00012496.

Cardiovascular Adverse Reactions During Antipsychotic Treatment: Results of AMSP, A Drug Surveillance Program Between 1993 and 2013.

BACKGROUND: Cardiovascular diseases are still the leading cause of global mortality. Some antipsychotic agents can show severe cardiovascular side effects and are also associated with metabolic syndrome. METHODS: This observational study was based on data of AMSP (Arzneimittelsicherheit in der Psychiatrie), a multicenter drug surveillance program in Austria, Germany and Switzerland, that recorded severe drug reactions in psychiatric inpatients. RESULTS: A total of 404 009 inpatients were monitored between 1993 and 2013, whereas 291 510 were treated with antipsychotics either in combination or alone. There were 376 cases of severe cardiovascular adverse reactions reported in the given timespan, yielding a relative frequency of 0.13%. The study revealed that incidence rates of cardiovascular adverse reactions were highest during treatment with ziprasidone (0.35%), prothipendyl (0.32%), and clozapine (0.23%). The lowest rate of cardiovascular symptoms occurred during treatment with promethazine (0.03%) as well as with aripiprazole (0.06%). The most common clinical symptoms were orthostatic collapse and severe hypotonia, sinustachycardia, QTc prolongation, myocarditis, and different forms of arrhythmia. The dosage at the timepoint when severe cardiovascular events occurred was not higher in any of the given antipsychotics than in everyday clinical practice and was in average therapeutic ranges. In terms of subclasses of antipsychotics, no significant statistical difference was seen in the overall frequencies of adverse reactions cases, when first-generation high potency, first-generation low potency, and second-generation antipsychotics were compared. Thirty percent of adverse events among second-generation antipsychotics were induced by clozapine. CONCLUSIONS: Our findings on cardiovascular adverse reactions contribute to a better understanding of cardiovascular risk profiles of antipsychotic agents in inpatients.

Severe parkinsonism under treatment with antipsychotic drugs.

The aim of the study was to assess rates of severe parkinsonism related to different antipsychotic drugs (APDs) using data from an observational pharmacovigilance programme in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP). Data on APD utilization and reports of severe APD-induced parkinsonism were collected in 99 psychiatric hospitals in Austria, Germany and Switzerland during the period 2001-2016. Of 340,099 patients under surveillance, 245,958 patients were treated with APDs for the main indications of schizophrenic disorders, depression, mania and organic mental disorders. A total of 200 events of severe APD-induced parkinsonism were identified (0.08%). First-generation low-potency APDs were significantly less often implicated (0.02%) than second-generation APDs (0.07%) and first-generation high-potency APDs (0.16%). Among the second-generation APDs, amisulpride and risperidone ranked highest. The phenothiazines were associated with significantly lower rates of severe parkinsonism (0.02%) than those of the butyrophenones (0.11%) and thioxanthenes (0.12%). In 71 cases (35.5%), more than 1 drug was considered responsible for the induction of severe parkinsonism. In 44 patients (22.0%), the symptoms were extremely severe, leading to complete immobility and/or massive complications such as pneumonia and severe injuries due to falls. Higher age (> 60 years) was associated with significantly higher rates of severe parkinsonism, as were the diagnoses of schizophrenic disorder or mania. The large number of patients included in the present survey allows for the comparison of severe parkinsonism rates related to different APD classes and single APDs. The first-generation low-potency APDs had significantly reduced risk of severe parkinsonism compared not only to high potency but also to second-generation APDs.

Translating the BDI and BDI-II into the HAMD and vice versa with equipercentile linking.

AIMS: The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale. METHODS: We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method. RESULTS: The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of -20 and -10 with the BDI of -29 and -15 and with the BDI-II of -35 and -16. CONCLUSIONS: The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research.

Seizure rates under treatment with antipsychotic drugs: Data from the AMSP project.

Objectives: The study aimed to assess seizure rates related to different antipsychotic drugs (APDs) in a clinical setting using data from the drug safety programme Arzneimittelsicherheit in der Psychiatrie (AMSP).Methods: Psychotropic drug use data and reports of APD-related seizures were collected in 89 psychiatric hospitals in Austria, Germany and Switzerland from 1993 to 2015.Results: Of 475,096 patients under surveillance, 320,383 patients were treated with APDs for the main indications of schizophrenic disorders, mood disorders and organic disorders. A total of 144 APD-related tonic clonic seizures were identified (0.04%). The butyrophenones ranked slightly lower (0.03%) compared to the phenothiazines, thioxanthenes and second-generation APDs (0.05% each). No significant differences were observed when comparing first- and second-generation APDs. Clozapine was related to the highest seizure rate (0.18%). In 107 cases (74.3%), more than one drug was considered responsible for seizure induction. With the exception of clozapine, seizures imputed to a single APD were in the clear minority. Seizure rates under the combinations of APDs with tricyclic antidepressants or lithium, as well as under triple combinations of APDs, were increased approximately two-fold. Young age (≤30 years), the male gender, and diagnosis of schizophrenic disorder were associated with significantly higher seizure rates (P < 0.05).Conclusions: Closely reflecting daily clinical practice, the present results provide supplementary information regarding APD therapy for patients not only at risk for seizures but also seizure-unaffected psychiatric inpatients.

Efficacy of extended clinical management, group CBT, and group plus individual CBT for major depression: Results of a two-year follow-up study.

OBJECTIVE: Cognitive therapy has gained prominence in the treatment of major depression, however, little is known about its long-term benefits when delivered during inpatient treatment or combined with outpatient treatment with severely ill inpatients (HAM-D > 20). METHOD: To evaluate this question, we conducted a randomized controlled trial investigating the efficacy of extended clinical management (E-CM), psychoeducational cognitive behavioural group therapy (PCBT-G) or PCBT-G and 16 outpatient individual treatment sessions (PCBT-G+I). All patients were treated with pharmacotherapy. 177 inpatients with DSM-IV major depression were randomized either to E-CM or PCBT-G or PCBT-G+I. Outcome measures were collected in the hospital at pre- and posttreatment and following discharge into the community every six months for two years. We compared the study groups on symptom changes, psychosocial functioning, knowledge about depression and rehospitalization. RESULTS: All three treatment interventions are equally effective at reducing depressive symptoms and increasing psychosocial functioning at posttreatment. There was significant group by time interaction for knowledge about depression in favor of PCBT-G and PCBT-G+I over E-CM. We did not find significantly lower rehospitalisation rates at the two-year follow-up for PCBT-G+I compared to E-CM, however, comparing PCBT-G to E-CM. CONCLUSIONS: We conclude that with cognitive psychoeducational group therapy a successful, in the long-term other interventions superior psychological intervention for major depression is available as gains were sustained for two years following discharge from the hospital. More research is needed to evaluate the long-term impact of group treatment starting in inpatient treatment.

Suicidal Ideation and Suicidal Behavior as Rare Adverse Events of Antidepressant Medication: Current Report from the AMSP Multicenter Drug Safety Surveillance Project.

Background: Suicidal ideations, suicide attempts, and fatal suicides are rare adverse drug reactions to antidepressant drugs, but they essentially are clinically relevant. Drawing on a larger dataset of the European drug surveillance program, the present naturalistic study updates a previous contribution (Stübner et al., 2010). Methods: First an analysis of the comprehensive data collected in 81 psychiatric hospitals from 1993 to 2014 by the European drug surveillance program Arzneimittelsicherheit in der Psychiatrie was made. All documented single cases of suicidal ideations or behavior judged as adverse drug reactions to antidepressant drugs were carefully assessed as to their clinical features and drug prescriptions. Results: Among 219,635 adult hospitalized patients taking antidepressant drugs under surveillance, 83 cases of suicidal adverse drug reactions occurred (0.04%): 44 cases of suicidal ideation, 34 attempted suicides, and 5 committed suicides were documented. Restlessness was present in 42 patients, ego-dystonic intrusive suicidal thoughts or urges in 39 patients, impulsiveness in 22 patients, and psychosis in 7 patients. Almost all adverse drug reactions occurred shortly after beginning antidepressant drug medication or increasing the dosage. Selective serotonin reuptake inhibitors caused a higher incidence of suicidal ideation and suicidal behavior as adverse drug reactions than noradrenergic and specific serotonergic antidepressants or tricyclic antidepressants, as did monotherapy consisting of one antidepressant drug, compared to combination treatments. Conclusions: The study supports the view that antidepressant drug-triggered suicidal ideation and suicidal behavior (primarily with selective serotonin reuptake inhibitors) are rare. Special clinical features (restlessness, ego-dystonic thoughts or urges, impulsiveness) may be considered as possible warning signs. A combination therapy might be preferable to antidepressant drug monotherapy when beginning treatment.